Antimicrobial Resistance in *Escherichia coli*

*Mario Galindo-Méndez*

#### **Abstract**

In the last decades, antimicrobial resistance has become a global threat to public health systems worldwide. Among those bacteria that pose the greatest threat to human health because of its growing resistance to antibiotics are the members of the *Enterobacteriaceae* family, particularly *Escherichia coli* and *Klebsiella* spp. Among the different antibiotic-resistant mechanisms developed by bacteria, the ones found in *Enterobacteriaceae* are more diverse than those in other families and include resistance to different antibiotic groups, advantages that partially explain why these microorganisms are among the most common causes of antibiotic-resistant bacterial infections in humans. Due to the continuously increasing number of infections caused by multidrug-resistant *E. coli* due to its ease of transmission via the fecaloral route among humans and from environmental sources, the understanding of the epidemiology of these strains and their mechanisms of resistance are key components in the fight against these infections.

**Keywords:** antimicrobial resistance, multidrug resistance, antibiotics, *Escherichia coli*, *Enterobacteriaceae*

#### **1. Introduction**

*Escherichia coli* is one of the most studied bacteria in the world and is arguably the best understood of all model microorganisms [1]. In the context of human and animal ecology, this microorganism participates as both a commensal of the gut, being one the first bacterial species to colonize it right after birth [2], and one of the most important human and animal pathogens, being able to cause intestinal and extra-intestinal infections. In humans, *E. coli* is the most frequent cause of urinary tract infections and has been identified as the causative agent of disease in practically every anatomical site of the human body, causing appendicitis, pneumonia, bloodstream, gastrointestinal infections, skin abscesses, intra-amniotic and puerperal infection in pregnant women, meningitis and endocarditis. Furthermore, *E. coli* can cause both community-acquired infections and health care-related infections, and is able to cause disease in all age groups.

Since the introduction of penicillin in the 1940s, which started the era of antibiotics, these agents have been recognized as one of the greatest advances in modern medicine and a turning point in human history. In 1900, infectious disease was a leading cause of death; in 2000, infectious diseases were responsible for only a small percentage of deaths in developed nations [3]. Unfortunately for humans, bacteria have evolved different mechanisms that have rendered them resistant to

antibiotics, to the point that since not long ago antimicrobial resistance has become a global threat to public health systems worldwide.

The ability of bacteria to develop resistance against antibiotics began soon after their introduction, as penicillin resistance by *S. aureus* was identified just a few years after its introduction in hospitalized patients [4]. In the case of *E. coli*, resistance against antibiotics has been steadily increasing since the first reported cases and, due to its impact in human health, is now included, along with the rest of the *Enterobacteriaceae* family, in the World Health Organization's (WHO) list of the 12 families of bacteria that pose the greatest threat to human health [5].

The contribution of *E. coli* to the antimicrobial resistance phenomenon should be analyzed under two different, but complementary, contexts that at some point meet in one common issue: a broad impact on human health. These two perspectives include the increasing number of infections worldwide caused by multidrugresistant *E. coli* strains *per se* and the ability of this bacterium to transmit its genetic-resistant traits to other bacteria. *E. coli* has evolved these two attributes that have made this microorganism such a key player in the antibiotic resistance pandemic due to its ease of transmission among humans and from animals to humans via the fecal-oral route. Secondly, the microorganism's ability to colonize the gut of humans and animals allow it to be in close interaction with an abounding number of different bacteria, interaction that grant *E. coli* the duality to behave as a donor of genetic material to other bacteria and the ability to acquire resistance genes from other microorganisms.

This chapter describes the human actions that have contributed to the development of *E. coli* resistance to antibiotics, including the major impact of hygiene on the transmission and maintenance of its multidrug-resistant strains, and the known mechanisms developed by this organism to resist the actions of commonly used antibiotics.

#### **2. Onset and spread of** *E. coli* **resistance to antibiotics**

The emergence of antibacterial resistance in *E. coli* and other bacteria is multifactorial, but has paralleled the incorporation of these agents into the therapeutic arsenal in human and veterinary medicine. Data show that *E. coli* present the highest rates of resistance against those antibiotics that have been in use the longest time [6], as is evidenced by the high resistance rate worldwide against sulfonamides [7], whose use in humans started in the 1930s and its first *E. coli*-resistant clones were identified as early as 1950 [6]. Additionally, it is of no coincidence that those regions of the world with the highest consumption of antibiotics are low- to midincome countries (**Table 1**), whose antibiotic-resistant rates are higher than those found in high-income nations.

Antibiotic resistance (AR) is largely believed to be the sole result of human activity and antibiotic chemotherapy; however, genomic studies of human bacterial commensals and environmental bacteria have revealed the presence of considerable numbers of resistance determinants within their genomes [9] that were not acquired from horizontal transmission and predated the clinical introduction of antibiotics. This type of AR is known as intrinsic resistance and provides a selective benefit for the producing strains by inhibiting or eliminating other bacteria competing for resources. Intrinsic resistance differentiates from the newly developed extrinsic antibiotic resistance in that in the former there is no contribution of human activities and the latter is mainly driven by antibiotic selection pressure [10]. In the current era of increasing AR and lack of new antibacterial agents, the study of intrinsic resistance becomes highly attractive as a new mechanism to counteract

**181**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

*Countries with the highest antibiotic consumption in the world.*

certain antibiotics [12].

**Table 1.**

infections (**Table 2**).

tions and lack of new antibiotics developed [19].

**2.1 Overuse/inappropriate prescribing**

bacterial resistance, as inhibition of elements that comprise the intrinsic resistome renders bacteria hyper-susceptible to antibiotics [11]. In the case of Gram-negative bacteria, like *E. coli*, two major contributors to the bacterium intrinsic resistance are its outer membrane, which is impermeable to many molecules, and its expression of numerous efflux pumps, that effectively reduce the intracellular concentration of

**Country Daily doses per 1000 inhabitants/day (% of total) [8]**

Mongolia 64.4 Iran 38.8 Turkey 38.2 Sudan 35.3 Serbia 31.6 Montenegro 29.3 Romania 28.5

The acquired, or extrinsic, and continuously increasing resistance of *E. coli* to antibiotics is already considered a major public health problem around the world. In 2018, more than half of the *Escherichia coli* isolates reported to the European Centre for Disease Prevention and Control were resistant to at least one antimicrobial group under surveillance, and combined resistance to several antimicrobial groups was frequent [13]; in the United States in 2017, the national prevalence of extended spectrum β-lactamases (ESBL)-producing *E. coli* strains isolated from urinary tract infections (UTI) was 15.7%, whereas levofloxacin and trimethoprimsulfamethoxazole-resistant rates were ≥24% among all isolates [14]. In developing countries the situation worsens, as reported by national surveillance data from Mexico, China and Turkey, where *E. coli*-resistant strains has been shown to have a prevalence >40% to cephalosporins, quinolones and trimethoprim/sulfamethoxazole (TSX), drugs widely used around the world to empirically treat bacterial

During 1945, just a few years after the introduction into clinical practice of penicillin, Alexander Fleming warned the world about antibiotic overuse, warning that became reality a few years later when the first *S. aureus* strain was reported to be resistant to penicillin. Several human activities have been identified as key drivers of the current AR crisis, but it has been demonstrated that the overuse of antibiotics clearly influences the evolution of resistance [18]. The reported actions that have led to the overuse of antibiotics are multifactorial and include different players in different industries such as the health, the livestock and the pharmaceutical industries. Examples of these actions comprise inappropriate prescription of antibiotics by healthcare providers, extensive use of antibiotics in livestock and fish farming, patients not following antibiotic treatment regimes, poor hygiene, bacterial muta-

One of the most significant factors that have contributed to the current antibacterial resistance crisis is the rapid evolution of bacteria under selective antibiotic pressure, since a continuous interaction between any given antibiotic and bacteria is an important aspect for the increase in multidrug-resistant strains [20].


**Table 1.**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

families of bacteria that pose the greatest threat to human health [5].

**2. Onset and spread of** *E. coli* **resistance to antibiotics**

a global threat to public health systems worldwide.

other microorganisms.

found in high-income nations.

antibiotics.

antibiotics, to the point that since not long ago antimicrobial resistance has become

The ability of bacteria to develop resistance against antibiotics began soon after their introduction, as penicillin resistance by *S. aureus* was identified just a few years after its introduction in hospitalized patients [4]. In the case of *E. coli*, resistance against antibiotics has been steadily increasing since the first reported cases and, due to its impact in human health, is now included, along with the rest of the *Enterobacteriaceae* family, in the World Health Organization's (WHO) list of the 12

The contribution of *E. coli* to the antimicrobial resistance phenomenon should be analyzed under two different, but complementary, contexts that at some point meet in one common issue: a broad impact on human health. These two perspectives include the increasing number of infections worldwide caused by multidrugresistant *E. coli* strains *per se* and the ability of this bacterium to transmit its

genetic-resistant traits to other bacteria. *E. coli* has evolved these two attributes that have made this microorganism such a key player in the antibiotic resistance pandemic due to its ease of transmission among humans and from animals to humans via the fecal-oral route. Secondly, the microorganism's ability to colonize the gut of humans and animals allow it to be in close interaction with an abounding number of different bacteria, interaction that grant *E. coli* the duality to behave as a donor of genetic material to other bacteria and the ability to acquire resistance genes from

This chapter describes the human actions that have contributed to the development of *E. coli* resistance to antibiotics, including the major impact of hygiene on the transmission and maintenance of its multidrug-resistant strains, and the known mechanisms developed by this organism to resist the actions of commonly used

The emergence of antibacterial resistance in *E. coli* and other bacteria is multifactorial, but has paralleled the incorporation of these agents into the therapeutic arsenal in human and veterinary medicine. Data show that *E. coli* present the highest rates of resistance against those antibiotics that have been in use the longest time [6], as is evidenced by the high resistance rate worldwide against sulfonamides [7], whose use in humans started in the 1930s and its first *E. coli*-resistant clones were identified as early as 1950 [6]. Additionally, it is of no coincidence that those regions of the world with the highest consumption of antibiotics are low- to midincome countries (**Table 1**), whose antibiotic-resistant rates are higher than those

Antibiotic resistance (AR) is largely believed to be the sole result of human activity and antibiotic chemotherapy; however, genomic studies of human bacterial commensals and environmental bacteria have revealed the presence of considerable numbers of resistance determinants within their genomes [9] that were not acquired from horizontal transmission and predated the clinical introduction of antibiotics. This type of AR is known as intrinsic resistance and provides a selective benefit for the producing strains by inhibiting or eliminating other bacteria competing for resources. Intrinsic resistance differentiates from the newly developed extrinsic antibiotic resistance in that in the former there is no contribution of human activities and the latter is mainly driven by antibiotic selection pressure [10]. In the current era of increasing AR and lack of new antibacterial agents, the study of intrinsic resistance becomes highly attractive as a new mechanism to counteract

**180**

*Countries with the highest antibiotic consumption in the world.*

bacterial resistance, as inhibition of elements that comprise the intrinsic resistome renders bacteria hyper-susceptible to antibiotics [11]. In the case of Gram-negative bacteria, like *E. coli*, two major contributors to the bacterium intrinsic resistance are its outer membrane, which is impermeable to many molecules, and its expression of numerous efflux pumps, that effectively reduce the intracellular concentration of certain antibiotics [12].

The acquired, or extrinsic, and continuously increasing resistance of *E. coli* to antibiotics is already considered a major public health problem around the world. In 2018, more than half of the *Escherichia coli* isolates reported to the European Centre for Disease Prevention and Control were resistant to at least one antimicrobial group under surveillance, and combined resistance to several antimicrobial groups was frequent [13]; in the United States in 2017, the national prevalence of extended spectrum β-lactamases (ESBL)-producing *E. coli* strains isolated from urinary tract infections (UTI) was 15.7%, whereas levofloxacin and trimethoprimsulfamethoxazole-resistant rates were ≥24% among all isolates [14]. In developing countries the situation worsens, as reported by national surveillance data from Mexico, China and Turkey, where *E. coli*-resistant strains has been shown to have a prevalence >40% to cephalosporins, quinolones and trimethoprim/sulfamethoxazole (TSX), drugs widely used around the world to empirically treat bacterial infections (**Table 2**).

During 1945, just a few years after the introduction into clinical practice of penicillin, Alexander Fleming warned the world about antibiotic overuse, warning that became reality a few years later when the first *S. aureus* strain was reported to be resistant to penicillin. Several human activities have been identified as key drivers of the current AR crisis, but it has been demonstrated that the overuse of antibiotics clearly influences the evolution of resistance [18]. The reported actions that have led to the overuse of antibiotics are multifactorial and include different players in different industries such as the health, the livestock and the pharmaceutical industries. Examples of these actions comprise inappropriate prescription of antibiotics by healthcare providers, extensive use of antibiotics in livestock and fish farming, patients not following antibiotic treatment regimes, poor hygiene, bacterial mutations and lack of new antibiotics developed [19].

#### **2.1 Overuse/inappropriate prescribing**

One of the most significant factors that have contributed to the current antibacterial resistance crisis is the rapid evolution of bacteria under selective antibiotic pressure, since a continuous interaction between any given antibiotic and bacteria is an important aspect for the increase in multidrug-resistant strains [20].


#### **Table 2.**

Escherichia coli *antibiotic resistance rates to different antibiotics.*

Unfortunately, overuse and inappropriate prescription of these drugs are two large contributors to such issue. In any given antibiotic treatment against a bacterial infection, susceptible bacteria will be killed; if properly targeted, the pathogenic microorganism will be eradicated; however, along infecting bacteria, those members of the individual's microbiota, sensitive to the antibiotic in use, will also be wiped out. In case resistant microorganisms exist, either belonging to the normal microbiota or the pathogenic microorganisms being targeted, these survivors will replicate and will become the prevailing strain within the respective anatomical site.

The discovery and use of antibiotics have revolutionized the field of medicine and saved millions of lives each year; unfortunately, seen as the "miracle drug," healthcare providers and patients around the world have abused their use. Despite the marked increase of infections caused by multidrug-resistant bacteria around the world, the global response to this crisis has been inadequate, as people not only continue to misuse antibiotics but have continuously increased their abuse. Using a global database of antibiotic sales, Klein et al. [21] found that the antibiotic consumption rate around the world increased dramatically from 11.3 daily doses/1000 inhabitants per day to 15.7, an increase of 39%, between 2000 and 2015. In this same study, it was reported that the mean antibiotic consumption rate was primarily driven by the consumption in low- and mid-income countries, as no coincidence present the highest prevalence of multi drug-resistant bacteria-related infections. To make matters worse, the consumption of last-resort antibiotics such as carbapenems and colistin is also on the rise [21], situation that is consistent with the appearance of *E. coli*-resistant strains to these agents. To date, resistance of this organism to carbapenems is rare, with its prevalence depending on the area of the world under study, but not exceeding 3% [22]. However, in the future, an increase of resistance to this agent might be seen in *E. coli*, as the enzymes responsible for its hydrolysis, and thus inactivation, carbapenemases, are encoded mainly on plasmids, and are highly transmissible [23].

A key contributor to the increasing selective pressure of antibiotics is their overprescription. Recent data indicates that over 70% of prescribed antibiotics by primary care providers in the United States are inappropriate, the majority of which are for acute respiratory tract infections [24]; unfortunately, this rate of antibiotic misuse is probably a situation found in most countries. Coincidently, ciprofloxacin, one of the two most likely antibiotic to be prescribed inappropriately [24] is one to which *E. coli* present the highest rates of resistance around the world [15–17].

In addition to the contribution of the abuse of antibiotics to the selection of resistance, Zhang et al. [25] found epidemiological evidence that antibiotic resistance and *E. coli* diarrheagenic virulence phenotypes might be partially linked. They found that subjects with diarrhea had more frequent use of antibiotics before their onset of symptoms, linkage that might be explained as antibiotics might disrupt the intestinal microbiota, allowing overgrowth of resistant pathogens [25].

**183**

colonization [31].

**2.3 Hygiene/fecal colonization**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

animals are transmitted to humans via contaminated meat.

Antibiotics are used in livestock to treat clinical disease, to prevent and control common disease events, and to enhance animal growth [26]. Unfortunately, this use of antibiotics has favored spread and persistence of resistant bacteria in humans by means of two different mechanisms: (a) human ingestion of antibiotics by means of the antibiotic-contaminated meat that enters the body and induces selective pressure on the host's microbiota and (b) resistant bacteria found in the gut of food

When livestock are treated or are provided with antibiotics, these agents exercise the same selective pressure on their microbiota as when humans ingest these drugs; thus, overuse of antibiotics on food animals has led to a high colonization rate of intestinal bacteria, including members of the *Enterobacteriaceae* family, such as *E. coli* and *Klebsiella* spp., that become resistant to different antimicrobials. Different studies around the world have shown that ready-to-eat animal products are contaminated with *E. coli* strains resistant to different kinds of antibiotics, mainly to β-lactams by means of the bacterial production of extended spectrum β-lactamases (ESBL) [27, 28]. These studies show that animal meat contaminated with *E. coli*-resistant strains is far more prevalent in developing than in developed nations, probably due to different hygiene habits; German studies have reported a prevalence of ESBL-contaminated meat of 24.1% [27], whereas in Mexico this prevalence has been reported to be above 60.0% [28]. *E. coli* strains isolated in meat have also shown resistance to other antibiotics, including to last-resort ones such as carbapenems [29] and colistin [30]. If this contaminated meat is ingested undercooked by humans, gut colonization is likely, establishing a reservoir for future antibiotic-resistant infections, as Ruppé et al. have shown that people with high gut colonization rates of ESBL-producing *E. coli* strains present higher risk to develop urinary tract infections with these clones than patients with no ESBL gut

**Figure 1** shows a resumed representation of the main reservoirs, including

Higher consumption of antibiotics in unprivileged areas of the world plays a key role in the emergence and maintenance of antimicrobial resistance due to selective pressure by these agents on resident microbiota. However, studies have shown that inhabitants of these areas can be highly colonized with antibiotic-resistant *E. coli* strains despite not being in contact with antibiotics for 3–6 months [28], indicating that additional factors play important roles in the increased prevalence of AR worldwide. Global evidence suggests that elements in people's environment such as poor waste, non-potable drinking water, housing overcrowding and lack of hygiene

The ability of *E. coli* to colonize different environments, including the gut of humans and animals, has provided this organism with the evolutionary advantage to acquire antibiotic resistance traits from other bacteria within its environment, as well as to be easily transmitted via the fecal-oral route. The gut microbiota of humans can harbor more than 1000 different antibiotic-resistant genes [33] and transmission of these traits among gut commensals is a constant phenomenon. Major examples of the transference of resistance genes between environmental bacteria, including gut commensals, and human pathogens, are the bla*CTX-M* genes, which is the most prevalent ESBL gene in *E. coli* and *Klebsiella* spp., and

livestock, of antibiotic-resistant *E. coli* and their interaction with humans.

facilitate the development and transmission of resistant bacteria [32].

**2.2 Use of antibiotics in livestock**

#### **2.2 Use of antibiotics in livestock**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

Escherichia coli *antibiotic resistance rates to different antibiotics.*

*ND: not done.*

**Table 2.**

**Country Resistance rates (%)**

Unfortunately, overuse and inappropriate prescription of these drugs are two large contributors to such issue. In any given antibiotic treatment against a bacterial infection, susceptible bacteria will be killed; if properly targeted, the pathogenic microorganism will be eradicated; however, along infecting bacteria, those members of the individual's microbiota, sensitive to the antibiotic in use, will also be wiped out. In case resistant microorganisms exist, either belonging to the normal microbiota or the pathogenic microorganisms being targeted, these survivors will replicate and

Mexico [15] 54.4 59.0 62.1 China [16] 52.4 69.8 ND Turkey [17] 40.7 47.2 58.0

**Cephalosporins Quinolones TSX**

The discovery and use of antibiotics have revolutionized the field of medicine and saved millions of lives each year; unfortunately, seen as the "miracle drug," healthcare providers and patients around the world have abused their use. Despite the marked increase of infections caused by multidrug-resistant bacteria around the world, the global response to this crisis has been inadequate, as people not only continue to misuse antibiotics but have continuously increased their abuse. Using a global database of antibiotic sales, Klein et al. [21] found that the antibiotic consumption rate around the world increased dramatically from 11.3 daily doses/1000 inhabitants per day to 15.7, an increase of 39%, between 2000 and 2015. In this same study, it was reported that the mean antibiotic consumption rate was primarily driven by the consumption in low- and mid-income countries, as no coincidence present the highest prevalence of multi drug-resistant bacteria-related infections. To make matters worse, the consumption of last-resort antibiotics such as carbapenems and colistin is also on the rise [21], situation that is consistent with the appearance of *E. coli*-resistant strains to these agents. To date, resistance of this organism to carbapenems is rare, with its prevalence depending on the area of the world under study, but not exceeding 3% [22]. However, in the future, an increase of resistance to this agent might be seen in *E. coli*, as the enzymes responsible for its hydrolysis, and thus inactivation, carbapenemases, are encoded mainly on plas-

A key contributor to the increasing selective pressure of antibiotics is their overprescription. Recent data indicates that over 70% of prescribed antibiotics by primary care providers in the United States are inappropriate, the majority of which are for acute respiratory tract infections [24]; unfortunately, this rate of antibiotic misuse is probably a situation found in most countries. Coincidently, ciprofloxacin, one of the two most likely antibiotic to be prescribed inappropriately [24] is one to which *E. coli* present the highest rates of resistance around the world [15–17]. In addition to the contribution of the abuse of antibiotics to the selection of resistance, Zhang et al. [25] found epidemiological evidence that antibiotic resistance and *E. coli* diarrheagenic virulence phenotypes might be partially linked. They found that subjects with diarrhea had more frequent use of antibiotics before their onset of symptoms, linkage that might be explained as antibiotics might disrupt the

intestinal microbiota, allowing overgrowth of resistant pathogens [25].

will become the prevailing strain within the respective anatomical site.

mids, and are highly transmissible [23].

**182**

Antibiotics are used in livestock to treat clinical disease, to prevent and control common disease events, and to enhance animal growth [26]. Unfortunately, this use of antibiotics has favored spread and persistence of resistant bacteria in humans by means of two different mechanisms: (a) human ingestion of antibiotics by means of the antibiotic-contaminated meat that enters the body and induces selective pressure on the host's microbiota and (b) resistant bacteria found in the gut of food animals are transmitted to humans via contaminated meat.

When livestock are treated or are provided with antibiotics, these agents exercise the same selective pressure on their microbiota as when humans ingest these drugs; thus, overuse of antibiotics on food animals has led to a high colonization rate of intestinal bacteria, including members of the *Enterobacteriaceae* family, such as *E. coli* and *Klebsiella* spp., that become resistant to different antimicrobials. Different studies around the world have shown that ready-to-eat animal products are contaminated with *E. coli* strains resistant to different kinds of antibiotics, mainly to β-lactams by means of the bacterial production of extended spectrum β-lactamases (ESBL) [27, 28]. These studies show that animal meat contaminated with *E. coli*-resistant strains is far more prevalent in developing than in developed nations, probably due to different hygiene habits; German studies have reported a prevalence of ESBL-contaminated meat of 24.1% [27], whereas in Mexico this prevalence has been reported to be above 60.0% [28]. *E. coli* strains isolated in meat have also shown resistance to other antibiotics, including to last-resort ones such as carbapenems [29] and colistin [30]. If this contaminated meat is ingested undercooked by humans, gut colonization is likely, establishing a reservoir for future antibiotic-resistant infections, as Ruppé et al. have shown that people with high gut colonization rates of ESBL-producing *E. coli* strains present higher risk to develop urinary tract infections with these clones than patients with no ESBL gut colonization [31].

**Figure 1** shows a resumed representation of the main reservoirs, including livestock, of antibiotic-resistant *E. coli* and their interaction with humans.

#### **2.3 Hygiene/fecal colonization**

Higher consumption of antibiotics in unprivileged areas of the world plays a key role in the emergence and maintenance of antimicrobial resistance due to selective pressure by these agents on resident microbiota. However, studies have shown that inhabitants of these areas can be highly colonized with antibiotic-resistant *E. coli* strains despite not being in contact with antibiotics for 3–6 months [28], indicating that additional factors play important roles in the increased prevalence of AR worldwide. Global evidence suggests that elements in people's environment such as poor waste, non-potable drinking water, housing overcrowding and lack of hygiene facilitate the development and transmission of resistant bacteria [32].

The ability of *E. coli* to colonize different environments, including the gut of humans and animals, has provided this organism with the evolutionary advantage to acquire antibiotic resistance traits from other bacteria within its environment, as well as to be easily transmitted via the fecal-oral route. The gut microbiota of humans can harbor more than 1000 different antibiotic-resistant genes [33] and transmission of these traits among gut commensals is a constant phenomenon. Major examples of the transference of resistance genes between environmental bacteria, including gut commensals, and human pathogens, are the bla*CTX-M* genes, which is the most prevalent ESBL gene in *E. coli* and *Klebsiella* spp., and

#### **Figure 1.**

*Reservoirs of antibiotic-resistant* E. coli *and their interaction with humans. Arrows show the* E. coli *flux from the different reservoirs.*

the OXA-48-type carbapenem-hydrolyzing β-lactamase genes, which are increasingly reported in *Enterobacteriaceae* around the globe. The potential origin of the bla*CTX-M* genes was identified in the chromosomal DNA of various environmental *Kluyvera* species [34], whereas that of OXA-48 was found to originate from the waterborne, environmental *Shewanella* species [35].

As many antibiotic resistance genes are associated with elements such as plasmids or transposons, and while the transfer of these elements may also occur through transformation or transduction, conjugation is often considered as the most likely responsible mechanism for the transmission of these traits [36]. The aforementioned ESBL and carbapenemase genes are primary examples of resistant genes with high impact on human health that have spread between bacteria via plasmid conjugation. Studies in China [37] have demonstrated that transmission via conjugation of ESBL genes in *E. coli* do occur even in the food chain, situation that partially explain the high fecal prevalence of ESBL-producing *E. coli* around the world.

The gut of humans and animals is a major reservoir of antibiotic-resistant *E. coli* and shedding of these strains through the feces of colonized individuals, livestock and domestic animals allows them to reach humans via contaminated water and food (see **Figure 1**). Human fecal colonization by antibiotic-resistant *E. coli* strains present the highest rates in deprived areas of the world, situation that begins since birth. Whereas in high-income nations the prevalence of *E. coli* strains resistant to antibiotics colonizing the gastrointestinal system of neonates is low [38], in lowincome countries the prevalence of *E. coli* strains resistant to antibiotics such as tetracycline, ampicillin and trimethoprim/sulfamethoxazole exceeds 50% [39]. Fecal colonization of humans by resistant *E. coli* is on the rise around the world since the mid-2000s and the situation has worsened as fecal colonization by strains resistant to last-resource antibiotics, such as colistin, has been recently reported in different countries [40, 41]. As the prevalence of fecal colonization by these *E. coli* strains increase, so will the number of human infections caused by them, as it has been previously shown that fecal colonization with resistant microorganisms increases the risk factor of developing urinary tract infections by a factor of 13.0 [31].

Antibiotic consumption has contributed to the selection of resistance and is largely accepted as one of the major drivers of AR development; however, the high

**185**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

prevalence of antibiotic resistance around the world, especially in low- and midincome countries, can be more likely attributed to the dissemination and maintenance of resistant clones via poor sanitation and lack of hygiene habits [32]. Ingestion of contaminated food and water, close contact with colonized animals and household members and abundance of flies are factors that contribute to the transmission of kl *E. coli* strains. As these conditions are considerably less frequent in developed areas of the world, this situation partially explains the reduced prevalence of these strains in these nations. However, due to the current globalization, resistant strains can easily be transmitted from one country to another. In a large cohort study of Dutch travelers to regions of the world with high prevalence of ESBL-producing bacteria, 34.3% subjects who were ESBL negative before travel had acquired these clones during their time abroad, with the highest number of acquisitions being among those who traveled to southern Asia, and remained colonized at 12 months after return [42]. Additionally, this same study showed that the estimated probability of onward transmission within households was 12%. Similar results were reported in a study in Spain, in which up to 66% of the isolates from patients with ESBL-producing *E. coli* infections were indistinguishable from those isolated from fecal samples from their household members [43]. These results indicate that acquisition of *E. coli*-resistant clones during travel is high and that transmission between household members can

maintain such clones in the community for long periods of time.

used in the treatment against this organism: the β-lactams.

lactam antibiotics are known as penicillin-binding proteins (PBPs).

**3. Antibiotic resistance mechanisms**

**3.1 Resistance to β-lactams**

As anthropogenic activities largely shape the resistome of different environments, transmission of resistant genes between bacteria in a community can be influenced by its contamination with human and animal feces and its impact is largely driven not by the presence of resistant bacteria but rather from the presence of human-related mobile resistance genes [44]. If poor sanitation, manifested by fecal contamination, of a given community is the key to transmit and maintain resistant clones, the reduction of antibiotic consumption will not be sufficient to control antimicrobial resistance. Thus, strategies to control the AR pandemic should also include improving sanitation conditions in all parts of the world.

Few microorganisms have shown the ability to develop resistance to as many classes of antibiotics as the *Enterobacteriaceae.* Of the large list of bacterial genus that belong to this family, *E. coli* is only surpassed by *Klebsiella* in the number of human infections associated to multidrug-resistant bacteria [15–17, 27] and the past two decades have witnessed major increases in the emergence and spread of *E. coli* resistance strains to major classes of antibiotics such as β-lactams, quinolones, aminoglycosides, sulfonamides and fosfomycin. Unfortunately, this resistance has spread to last resource antibiotic classes such as the polymyxins and carbapenems. The following sections will briefly described the resistance mechanisms developed by *E. coli* against one of the major antibiotic groups currently

Antibiotics belonging to the β-lactams class share a common feature: a threecarbon and one-nitrogen ring (beta-lactam ring), which is the molecular constituent responsible for the bacteriolytic mechanism of action of these agents against bacteria. β-Lactams act by inhibiting the bacterial synthesis of peptidoglycan, a vital constituent of the microorganism cell wall. The targets for the actions of beta-

#### *Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

the OXA-48-type carbapenem-hydrolyzing β-lactamase genes, which are increasingly reported in *Enterobacteriaceae* around the globe. The potential origin of the bla*CTX-M* genes was identified in the chromosomal DNA of various environmental *Kluyvera* species [34], whereas that of OXA-48 was found to originate from the

*Reservoirs of antibiotic-resistant* E. coli *and their interaction with humans. Arrows show the* E. coli *flux from* 

As many antibiotic resistance genes are associated with elements such as plasmids or transposons, and while the transfer of these elements may also occur through transformation or transduction, conjugation is often considered as the most likely responsible mechanism for the transmission of these traits [36]. The aforementioned ESBL and carbapenemase genes are primary examples of resistant genes with high impact on human health that have spread between bacteria via plasmid conjugation. Studies in China [37] have demonstrated that transmission via conjugation of ESBL genes in *E. coli* do occur even in the food chain, situation that partially explain the high fecal prevalence of ESBL-producing *E. coli* around

The gut of humans and animals is a major reservoir of antibiotic-resistant *E. coli* and shedding of these strains through the feces of colonized individuals, livestock and domestic animals allows them to reach humans via contaminated water and food (see **Figure 1**). Human fecal colonization by antibiotic-resistant *E. coli* strains present the highest rates in deprived areas of the world, situation that begins since birth. Whereas in high-income nations the prevalence of *E. coli* strains resistant to antibiotics colonizing the gastrointestinal system of neonates is low [38], in lowincome countries the prevalence of *E. coli* strains resistant to antibiotics such as tetracycline, ampicillin and trimethoprim/sulfamethoxazole exceeds 50% [39]. Fecal colonization of humans by resistant *E. coli* is on the rise around the world since the mid-2000s and the situation has worsened as fecal colonization by strains resistant to last-resource antibiotics, such as colistin, has been recently reported in different countries [40, 41]. As the prevalence of fecal colonization by these *E. coli* strains increase, so will the number of human infections caused by them, as it has been previously shown that fecal colonization with resistant microorganisms increases the risk factor of developing urinary tract infections by a factor of 13.0 [31]. Antibiotic consumption has contributed to the selection of resistance and is largely accepted as one of the major drivers of AR development; however, the high

waterborne, environmental *Shewanella* species [35].

**184**

the world.

**Figure 1.**

*the different reservoirs.*

prevalence of antibiotic resistance around the world, especially in low- and midincome countries, can be more likely attributed to the dissemination and maintenance of resistant clones via poor sanitation and lack of hygiene habits [32]. Ingestion of contaminated food and water, close contact with colonized animals and household members and abundance of flies are factors that contribute to the transmission of kl *E. coli* strains. As these conditions are considerably less frequent in developed areas of the world, this situation partially explains the reduced prevalence of these strains in these nations. However, due to the current globalization, resistant strains can easily be transmitted from one country to another. In a large cohort study of Dutch travelers to regions of the world with high prevalence of ESBL-producing bacteria, 34.3% subjects who were ESBL negative before travel had acquired these clones during their time abroad, with the highest number of acquisitions being among those who traveled to southern Asia, and remained colonized at 12 months after return [42]. Additionally, this same study showed that the estimated probability of onward transmission within households was 12%. Similar results were reported in a study in Spain, in which up to 66% of the isolates from patients with ESBL-producing *E. coli* infections were indistinguishable from those isolated from fecal samples from their household members [43]. These results indicate that acquisition of *E. coli*-resistant clones during travel is high and that transmission between household members can maintain such clones in the community for long periods of time.

As anthropogenic activities largely shape the resistome of different environments, transmission of resistant genes between bacteria in a community can be influenced by its contamination with human and animal feces and its impact is largely driven not by the presence of resistant bacteria but rather from the presence of human-related mobile resistance genes [44]. If poor sanitation, manifested by fecal contamination, of a given community is the key to transmit and maintain resistant clones, the reduction of antibiotic consumption will not be sufficient to control antimicrobial resistance. Thus, strategies to control the AR pandemic should also include improving sanitation conditions in all parts of the world.

#### **3. Antibiotic resistance mechanisms**

Few microorganisms have shown the ability to develop resistance to as many classes of antibiotics as the *Enterobacteriaceae.* Of the large list of bacterial genus that belong to this family, *E. coli* is only surpassed by *Klebsiella* in the number of human infections associated to multidrug-resistant bacteria [15–17, 27] and the past two decades have witnessed major increases in the emergence and spread of *E. coli* resistance strains to major classes of antibiotics such as β-lactams, quinolones, aminoglycosides, sulfonamides and fosfomycin. Unfortunately, this resistance has spread to last resource antibiotic classes such as the polymyxins and carbapenems. The following sections will briefly described the resistance mechanisms developed by *E. coli* against one of the major antibiotic groups currently used in the treatment against this organism: the β-lactams.

#### **3.1 Resistance to β-lactams**

Antibiotics belonging to the β-lactams class share a common feature: a threecarbon and one-nitrogen ring (beta-lactam ring), which is the molecular constituent responsible for the bacteriolytic mechanism of action of these agents against bacteria. β-Lactams act by inhibiting the bacterial synthesis of peptidoglycan, a vital constituent of the microorganism cell wall. The targets for the actions of betalactam antibiotics are known as penicillin-binding proteins (PBPs).

Bacteria have evolved different mechanisms of resistance against β-lactams: (a) Inactivation of these agents by the production of beta-lactamases; (b) decreased penetration of the antibiotic to the target site; (c) alteration of target site PBPs; and (d) efflux from the periplasmic space through specific pumping mechanism. However, in the case of *E. coli*, resistance to these antibiotics is mediated by the production of a group of enzymes referred as the "β-lactamases." These enzymes are ancient compounds, currently exceeding 2800 unique proteins, which emerged from environmental sources [45].

To date, β-lactamases are usually classified based on functional or structural criteria. Currently, the most widely used classification for these enzymes is the Ambler structural classification, which is based on sequence similarity, and separates these proteins into four classes: the classes A, C, and D of serine-β-lactamases and the class B of metallo-β-lactamases [46].

Gram-negative bacteria have evolved the production of different β-lactamases; in the case of *E. coli*, the most important ones from the medical point of view are the extended spectrum β-lactamases (ESBL), AmpC β-lactamases (AmpC) and the carbapenemases. Each of these groups of enzymes presents different spectrum of hydrolytic activity, thus presenting resistance to different types of β-lactams, as shown in **Table 3**.

#### *3.1.1 Extended spectrum β-lactamases (ESBL)*

Among the β-lactamases, ESBL are worthy of the attention of the scientific and medical community over the last decades because of their increasing prevalence as cause of antibiotic-resistant infections around the world. These enzymes can be produced by any member of the *Enterobacteriaceae*, but *Klebsiella* spp. and *E coli* are the predominant ESBL-producing genus.

ESBL belong mostly to class A of the Ambler classification, are generally plasmid encoded and confer resistance to those bacteria that produce them to penicillins, first-, second-, and third-generation cephalosporins and monobactams (e.g., aztreonam), but cannot hydrolyze cephamycins (cefoxitin) or carbapenems (imipenem, meropenem), and are inhibited by β-lactamase inhibitors such as clavulanic acid, tazobactam and sulbactam [47].


**187**

prescribed [53].

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

species [48].

high efficiency [50].

quency of transmission from 10<sup>−</sup><sup>7</sup>

When ESBL were first identified, most ESLB-related infections were caused by strains producing the TEM and SHV types. However, since then, ESBL CTX-M has emerged as the predominant type, both in humans and animals, in commensal organisms and in pathogenic strains and in community and healthcare-associated infections. Since the first isolation of SHV- and TEM-producing strains, more than 100 different variants of each type have been described and all have arisen from the original strains; contrary to the SHV and TEM types, CTX-M groups seem to have originated from the chromosomally encoded ESBL genes from different *Kluyvera*

HSV, TEM and CTX-M show different hydrolytic activities against different β-lactams. When first identified, SHV β-lactamases proved its activity against penicillins and first generation cephalosporins; as of today, the three sub-groups used to classify this group of enzymes present different antibiotic resistance phenotypes: (a) subgroup 2b hydrolyze penicillins and early cephalosporins (cephaloridine and cephalothin) and are strongly inhibited by clavulanic acid and tazobactam; (b) subgroup 2br are broad-spectrum β-lactamases that acquired resistance to clavulanic acid; and (c) subgroup 2be comprises ESBL that can also hydrolyze one or more oxyimino β-lactams (cefotaxime, ceftazidime, and aztreonam) [49]. In the case of TEM β-lactamases, the bacteria carrying these genes are able to hydrolyze penicillin and first generation cephalosporins such as cephaloridine; furthermore, TEM-1 is able to hydrolyze ampicillin at a greater rate than carbenicillin, oxacillin, or cephalothin, and has negligible activity against extended-spectrum cephalosporins [50]. Finally, CTX-M enzymes have the property of having potent hydrolytic activity against cefotaxime, with CTX-M-producing microorganisms showing cefotaxime MICs in the resistant range (>64 μg/ml), while ceftazidime MICs are usually in the apparently susceptible range (2 to 8 μg/ml); however, some CTX-M-type ESBLs may actually hydrolyze ceftazidime and confer resistance to this cephalosporin; aztreonam MICs are variable. CTX-M-type β-lactamases hydrolyze cefepime with

The exponential global increase in the number of infections caused by ESBLproducing strains has coincided with the appearance of the *CTX-M* genes. When originally reported, these strains were predominantly found in three geographic areas: South America, the Far East, and Eastern Europe. However, due to the extremely transferable plasmids which harbor bla*CTX-M* genes [49], with a fre-

increasingly reported as cause of human infections in every continent, to the point that it could be speculated that CTX-M-type ESBLs are now the most frequent ESBL type worldwide [50]. An additional factor that has been suggested as a key contributor to the dissemination of these clones is the frequent co-existence of bla*CTX-M* with genes conferring resistance to other classes of antibiotics like fluoroquinolones and aminoglycosides, situation that might lead to high rates of co-selection [51]. To date, over 150 CTX-M types have been identified and described (https:// www.lahey.org/studies/other.asp). These ESBL types have been grouped into five clusters (CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25) [52], with each cluster presenting different variants, and more variants constantly being described, as shown by the recent discovery of two novel ones, named *bla*CTX-M-14.2 and *bla*CTX-M-15.2 [53]. Out of the different CTX-M variants, different reports in different continents indicate that *bla*CTX-M-15, belonging to cluster CTX-M-1, is now the most prevalent ESBL in *E. coli* around the world [54]. The increasing predominance of the *bla*CTX-M-15 allele might be due to the powerful ability of this enzyme to hydrolyze different β-lactams, which probably offers the producing bacteria a selective advantage, especially when multiple antibiotics are concomitantly or consecutively

per donor cell [48], these strains are now

to 10<sup>−</sup><sup>2</sup>

#### **Table 3.**

*Spectrum of activity of the major types of β-lactamases produced by* Escherichia coli.

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

from environmental sources [45].

class B of metallo-β-lactamases [46].

*3.1.1 Extended spectrum β-lactamases (ESBL)*

the predominant ESBL-producing genus.

ESBL Penicillins

AmpC Penicillins

Carbapenemases New Delhi metallo-β-lactamase

oxacillinase-48

Carbapenem-hydrolyzing

clavulanic acid, tazobactam and sulbactam [47].

**β-Lactamase Spectrum of activity Inhibition by** 

First to third generation cephalosporins Monobactams

First to third generation cephalosporins Monobactams

All β-lactams except aztreonam

*Spectrum of activity of the major types of β-lactamases produced by* Escherichia coli.

All β-lactams except broad spectrum cephalosporins

shown in **Table 3**.

Bacteria have evolved different mechanisms of resistance against β-lactams: (a) Inactivation of these agents by the production of beta-lactamases; (b) decreased penetration of the antibiotic to the target site; (c) alteration of target site PBPs; and (d) efflux from the periplasmic space through specific pumping mechanism. However, in the case of *E. coli*, resistance to these antibiotics is mediated by the production of a group of enzymes referred as the "β-lactamases." These enzymes are ancient compounds, currently exceeding 2800 unique proteins, which emerged

To date, β-lactamases are usually classified based on functional or structural criteria. Currently, the most widely used classification for these enzymes is the Ambler structural classification, which is based on sequence similarity, and separates these proteins into four classes: the classes A, C, and D of serine-β-lactamases and the

Gram-negative bacteria have evolved the production of different β-lactamases; in the case of *E. coli*, the most important ones from the medical point of view are the extended spectrum β-lactamases (ESBL), AmpC β-lactamases (AmpC) and the carbapenemases. Each of these groups of enzymes presents different spectrum of hydrolytic activity, thus presenting resistance to different types of β-lactams, as

Among the β-lactamases, ESBL are worthy of the attention of the scientific and medical community over the last decades because of their increasing prevalence as cause of antibiotic-resistant infections around the world. These enzymes can be produced by any member of the *Enterobacteriaceae*, but *Klebsiella* spp. and *E coli* are

> **β-lactamase inhibitors**

Yes No

No Yes

No Yes

No Weak

**Activity against broad-spectrum cephalosporins**

ESBL belong mostly to class A of the Ambler classification, are generally plasmid encoded and confer resistance to those bacteria that produce them to penicillins, first-, second-, and third-generation cephalosporins and monobactams (e.g., aztreonam), but cannot hydrolyze cephamycins (cefoxitin) or carbapenems (imipenem, meropenem), and are inhibited by β-lactamase inhibitors such as

**186**

**Table 3.**

When ESBL were first identified, most ESLB-related infections were caused by strains producing the TEM and SHV types. However, since then, ESBL CTX-M has emerged as the predominant type, both in humans and animals, in commensal organisms and in pathogenic strains and in community and healthcare-associated infections. Since the first isolation of SHV- and TEM-producing strains, more than 100 different variants of each type have been described and all have arisen from the original strains; contrary to the SHV and TEM types, CTX-M groups seem to have originated from the chromosomally encoded ESBL genes from different *Kluyvera* species [48].

HSV, TEM and CTX-M show different hydrolytic activities against different β-lactams. When first identified, SHV β-lactamases proved its activity against penicillins and first generation cephalosporins; as of today, the three sub-groups used to classify this group of enzymes present different antibiotic resistance phenotypes: (a) subgroup 2b hydrolyze penicillins and early cephalosporins (cephaloridine and cephalothin) and are strongly inhibited by clavulanic acid and tazobactam; (b) subgroup 2br are broad-spectrum β-lactamases that acquired resistance to clavulanic acid; and (c) subgroup 2be comprises ESBL that can also hydrolyze one or more oxyimino β-lactams (cefotaxime, ceftazidime, and aztreonam) [49]. In the case of TEM β-lactamases, the bacteria carrying these genes are able to hydrolyze penicillin and first generation cephalosporins such as cephaloridine; furthermore, TEM-1 is able to hydrolyze ampicillin at a greater rate than carbenicillin, oxacillin, or cephalothin, and has negligible activity against extended-spectrum cephalosporins [50]. Finally, CTX-M enzymes have the property of having potent hydrolytic activity against cefotaxime, with CTX-M-producing microorganisms showing cefotaxime MICs in the resistant range (>64 μg/ml), while ceftazidime MICs are usually in the apparently susceptible range (2 to 8 μg/ml); however, some CTX-M-type ESBLs may actually hydrolyze ceftazidime and confer resistance to this cephalosporin; aztreonam MICs are variable. CTX-M-type β-lactamases hydrolyze cefepime with high efficiency [50].

The exponential global increase in the number of infections caused by ESBLproducing strains has coincided with the appearance of the *CTX-M* genes. When originally reported, these strains were predominantly found in three geographic areas: South America, the Far East, and Eastern Europe. However, due to the extremely transferable plasmids which harbor bla*CTX-M* genes [49], with a frequency of transmission from 10<sup>−</sup><sup>7</sup> to 10<sup>−</sup><sup>2</sup> per donor cell [48], these strains are now increasingly reported as cause of human infections in every continent, to the point that it could be speculated that CTX-M-type ESBLs are now the most frequent ESBL type worldwide [50]. An additional factor that has been suggested as a key contributor to the dissemination of these clones is the frequent co-existence of bla*CTX-M* with genes conferring resistance to other classes of antibiotics like fluoroquinolones and aminoglycosides, situation that might lead to high rates of co-selection [51].

To date, over 150 CTX-M types have been identified and described (https:// www.lahey.org/studies/other.asp). These ESBL types have been grouped into five clusters (CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25) [52], with each cluster presenting different variants, and more variants constantly being described, as shown by the recent discovery of two novel ones, named *bla*CTX-M-14.2 and *bla*CTX-M-15.2 [53]. Out of the different CTX-M variants, different reports in different continents indicate that *bla*CTX-M-15, belonging to cluster CTX-M-1, is now the most prevalent ESBL in *E. coli* around the world [54]. The increasing predominance of the *bla*CTX-M-15 allele might be due to the powerful ability of this enzyme to hydrolyze different β-lactams, which probably offers the producing bacteria a selective advantage, especially when multiple antibiotics are concomitantly or consecutively prescribed [53].

One of the key players in the global dissemination of CTX-M-15-producing *E. coli* strains is clone ST131. A study performed in *E. coli* ST131 strains isolated between 2002 and 2004, before de ESBL pandemic, showed that only 2% of those strains carried the *CTX-M-15* gene [55]; almost two decades later, ST131 is one of the main clones isolated in the worldwide spread of ESBL-producing *E. coli* [56], particularly subclone H30Rx [57]. How this *E. coli* clone went from being a nonfactor in the global ESBL transmission to a key player is probably multifactorial. Although ST131 strains are not considered hypervirulent, most of them show the presence of fluoroquinolone-resistant genes, they have the ability to be persistent gut colonizers even in the absence of antibiotic exposure, a condition that precedes some infections such as those in the urinary tract, and can be easily transmitted between people of all ages [58]. All of these factors have allowed this clone to be successful human pathogen, even before the spread of the ESBL genes; however, the acquisition by ST131 strains of the CTX-M-15 plasmid has made this *E. coli* lineage an even more successful pathogen and has probably exasperated the spread of such clone [59] and the rapid global spread of CTX-M-15-producing *E. coli*.

#### *3.1.2 AmpC β-lactamases (AmpC)*

Although the production of class A extended spectrum β-lactamases is the most common mechanism of resistance in *E. coli* against β-lactam agents, class C β-lactamases, or AmpC, can also confer those strains that produce them the ability to inactivate some of these compounds. Similar to ESBL, AmpC-producing organisms hydrolyze amino- and ureidopenicillins, oxyimino-β-lactams such as ceftazidime, ceftiofur, and aztreonam, but contrary to the former enzymes, AmpC also inactivates broad and extended-spectrum cephalosporins such as cephamycins (cefoxitin) and are not inhibited by β-lactamase inhibitors such as clavulanic acid. Neither ESBL nor AmpC confer bacteria resistance to carbapenems.

Originally, AmpC were described as chromosomally encoded enzymes and were detected in a few bacterial species such as *Enterobacter cloacae*, *Citrobacter freundii*, *Serratia marcescens, Acinetobacter* spp.*, Aeromonas* spp. and *Pseudomonas aeruginosa* [60]. As the use of β-lactamase inhibitors increased among the population, dissemination of AmpC genes among bacterial species began by means of horizontal travel through plasmids, phenomenon that led to the appearance of AmpC-resistant traits in bacteria that previously lacked such genes or expressed them at low levels, such as *E. coli*, *Klebsiella* spp. and *Shigella* spp. [60].

In *E. coli*, the subject of this chapter, resistance by AmpC can be plasmid encoded or due to the overexpression of the chromosomal AmpC genes. Contrary to the AmpC enzymes of other members of the *Enterobacteriaceae*, such as *Enterobacter* spp. and *Citrobacter freundii*, that of *E. coli* exhibits a non-inducible phenotype that is constitutive and its production depends on either the strength of the *ampC* promoter [61], the presence of >1 copy of the *ampC* gene, the incorporation of a stronger promoter sequence as part of an insertion element or by the acquisition of a strong promoter of other bacterial species [62]. As stated before, this organism can carry *ampC* genes either chromosomally or in plasmids; however, the latter is being recognized as the major threat since plasmid-encoded AmpC are easily transferable between bacterial species, can cause nosocomial outbreaks, is associated with multidrug resistance and, in combination with porin loss, may lead to resistance to carbapenems [63].

Bacterial resistance to β-lactams is a major public health problem around the world. Although ESBL production clearly exceeds AmpC production as the major cause of β-lactam resistance, the later enzymes are now being recognized as a growing problem in different members of the *Enterobacteriaceae*, including *E. coli*, as

**189**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

evidenced by the increasing number of these strains being reported across the globe. Sources of AmpC-producing *E. coli* strains include livestock [64], the environment [65], as colonizers of the human gut [66] and as cause of human infections. The prevalence of these strains isolated as causative agents of human infections varies, ranging from 2.0% reported in a Portuguese hospital [67] to 16.7% from three university hospitals in Iran [68] to 29.0% from five referral hospitals in Sudan [69]. When comparing the epidemiology of today's AmpC-producing *E. coli* to that of ESBL-producing bacteria of two decades ago, they present several common features: high gut colonization in both animals and humans, reduced prevalence as cause of human infections, environmental contamination by these multidrugresistant strains, higher isolation of both types of β-lactamase-producing strains in developing countries and their ability to be transmitted via plasmids among different bacterial species. As these two types of β-lactamase-producing strains behave similarly, it would be of no surprise to witness in the near future a booming increase of reports of infections caused by AmpC-producing strains, as witness two decades ago with ESBL. To make matter worse, infectious disease specialists are starting to see an increase of cases of *E. coli* strains that co-express ESBL and AmpC genes, complicating antimicrobial treatment even further. Different reports in India [70, 71] have shown that co-expression of bla*ESBL* and bla*AmpC* genes by *E. coli* strains isolated from different human infections is not uncommon, thus continuous monitoring of these resistance patterns is a necessity that will help prevent the

further spread of these multidrug-resistant microorganisms.

Since ESBL- and AmpC-producing *E. coli* are increasingly being reported as cause of severe infections, carbapenems represent in many cases the last option for effective treatment against these infections. Nevertheless, with an increasing consumption of these agents, carbapenem-resistant strains, particularly *Klebsiella* spp. and in a lesser degree *E. coli*, have become a public health concern, particularly in the hospital setting. Carbapenems bind to penicillin-binding proteins and induce spheroplast formation and cell lysis without filament formation. The carbapenems

include four agents: imipenem, meropenem, ertapenem and doripenem.

carbapenemase-producing *E. coli* from 0% in 2011 to 1.9% in 2017.

nem-hydrolyzing oxacillinase-48 (OXA-48) types [73, 75, 76].

*3.1.3.1 New Delhi metallo-β-lactamase*

As in the case of ESBL- and AmpC-producing *Enterobacteriaceae*, reports from different countries show that resistance to carbapenems has been constantly increasing in the last few years, becoming a public health problem. In Europe, 11 countries have reported an increase in the number of infections caused by carbapenemase-producing *Enterobacteriaceae* in the period from 2015 to 2018 [72] and in China, Tian et al. [73] have reported an increase in the prevalence of

The reported carbapenemases in *E. coli* primarily include *Klebsiella pneumoniae* carbapenemases (KPC), metallo-β-lactamases (MBL), including the VIM, IMP, GIM and NDM type, and oxacillin-hydrolyzing metallo-β-lactamases (OXA) [74]; however, different reports around the world have shown that the predominant types in *E. coli* are of the New Delhi metallo-β-lactamase (NDM-1) and carbape-

The New Delhi metallo-β-lactamase (NDM-1) and closely related enzymes are a group of zinc-requiring metallo-β-lactamases capable of hydrolyzing a broad range of β-lactams including all penicillins, cephalosporins and carbapenems, just sparing monobactams, and are among the most recently identified carbapenemases. The

*3.1.3 Carbapenemases*

#### *Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

clone [59] and the rapid global spread of CTX-M-15-producing *E. coli*.

Neither ESBL nor AmpC confer bacteria resistance to carbapenems.

as *E. coli*, *Klebsiella* spp. and *Shigella* spp. [60].

resistance to carbapenems [63].

Although the production of class A extended spectrum β-lactamases is the most common mechanism of resistance in *E. coli* against β-lactam agents, class C β-lactamases, or AmpC, can also confer those strains that produce them the ability to inactivate some of these compounds. Similar to ESBL, AmpC-producing organisms hydrolyze amino- and ureidopenicillins, oxyimino-β-lactams such as ceftazidime, ceftiofur, and aztreonam, but contrary to the former enzymes, AmpC also inactivates broad and extended-spectrum cephalosporins such as cephamycins (cefoxitin) and are not inhibited by β-lactamase inhibitors such as clavulanic acid.

Originally, AmpC were described as chromosomally encoded enzymes and were detected in a few bacterial species such as *Enterobacter cloacae*, *Citrobacter freundii*, *Serratia marcescens, Acinetobacter* spp.*, Aeromonas* spp. and *Pseudomonas aeruginosa* [60]. As the use of β-lactamase inhibitors increased among the population, dissemination of AmpC genes among bacterial species began by means of horizontal travel through plasmids, phenomenon that led to the appearance of AmpC-resistant traits in bacteria that previously lacked such genes or expressed them at low levels, such

In *E. coli*, the subject of this chapter, resistance by AmpC can be plasmid encoded or due to the overexpression of the chromosomal AmpC genes. Contrary to the AmpC enzymes of other members of the *Enterobacteriaceae*, such as *Enterobacter* spp. and *Citrobacter freundii*, that of *E. coli* exhibits a non-inducible phenotype that is constitutive and its production depends on either the strength of the *ampC* promoter [61], the presence of >1 copy of the *ampC* gene, the incorporation of a stronger promoter sequence as part of an insertion element or by the acquisition of a strong promoter of other bacterial species [62]. As stated before, this organism can carry *ampC* genes either chromosomally or in plasmids; however, the latter is being recognized as the major threat since plasmid-encoded AmpC are easily transferable between bacterial species, can cause nosocomial outbreaks, is associated with multidrug resistance and, in combination with porin loss, may lead to

Bacterial resistance to β-lactams is a major public health problem around the world. Although ESBL production clearly exceeds AmpC production as the major cause of β-lactam resistance, the later enzymes are now being recognized as a growing problem in different members of the *Enterobacteriaceae*, including *E. coli*, as

*3.1.2 AmpC β-lactamases (AmpC)*

One of the key players in the global dissemination of CTX-M-15-producing *E. coli* strains is clone ST131. A study performed in *E. coli* ST131 strains isolated between 2002 and 2004, before de ESBL pandemic, showed that only 2% of those strains carried the *CTX-M-15* gene [55]; almost two decades later, ST131 is one of the main clones isolated in the worldwide spread of ESBL-producing *E. coli* [56], particularly subclone H30Rx [57]. How this *E. coli* clone went from being a nonfactor in the global ESBL transmission to a key player is probably multifactorial. Although ST131 strains are not considered hypervirulent, most of them show the presence of fluoroquinolone-resistant genes, they have the ability to be persistent gut colonizers even in the absence of antibiotic exposure, a condition that precedes some infections such as those in the urinary tract, and can be easily transmitted between people of all ages [58]. All of these factors have allowed this clone to be successful human pathogen, even before the spread of the ESBL genes; however, the acquisition by ST131 strains of the CTX-M-15 plasmid has made this *E. coli* lineage an even more successful pathogen and has probably exasperated the spread of such

**188**

evidenced by the increasing number of these strains being reported across the globe. Sources of AmpC-producing *E. coli* strains include livestock [64], the environment [65], as colonizers of the human gut [66] and as cause of human infections. The prevalence of these strains isolated as causative agents of human infections varies, ranging from 2.0% reported in a Portuguese hospital [67] to 16.7% from three university hospitals in Iran [68] to 29.0% from five referral hospitals in Sudan [69].

When comparing the epidemiology of today's AmpC-producing *E. coli* to that of ESBL-producing bacteria of two decades ago, they present several common features: high gut colonization in both animals and humans, reduced prevalence as cause of human infections, environmental contamination by these multidrugresistant strains, higher isolation of both types of β-lactamase-producing strains in developing countries and their ability to be transmitted via plasmids among different bacterial species. As these two types of β-lactamase-producing strains behave similarly, it would be of no surprise to witness in the near future a booming increase of reports of infections caused by AmpC-producing strains, as witness two decades ago with ESBL. To make matter worse, infectious disease specialists are starting to see an increase of cases of *E. coli* strains that co-express ESBL and AmpC genes, complicating antimicrobial treatment even further. Different reports in India [70, 71] have shown that co-expression of bla*ESBL* and bla*AmpC* genes by *E. coli* strains isolated from different human infections is not uncommon, thus continuous monitoring of these resistance patterns is a necessity that will help prevent the further spread of these multidrug-resistant microorganisms.

#### *3.1.3 Carbapenemases*

Since ESBL- and AmpC-producing *E. coli* are increasingly being reported as cause of severe infections, carbapenems represent in many cases the last option for effective treatment against these infections. Nevertheless, with an increasing consumption of these agents, carbapenem-resistant strains, particularly *Klebsiella* spp. and in a lesser degree *E. coli*, have become a public health concern, particularly in the hospital setting. Carbapenems bind to penicillin-binding proteins and induce spheroplast formation and cell lysis without filament formation. The carbapenems include four agents: imipenem, meropenem, ertapenem and doripenem.

As in the case of ESBL- and AmpC-producing *Enterobacteriaceae*, reports from different countries show that resistance to carbapenems has been constantly increasing in the last few years, becoming a public health problem. In Europe, 11 countries have reported an increase in the number of infections caused by carbapenemase-producing *Enterobacteriaceae* in the period from 2015 to 2018 [72] and in China, Tian et al. [73] have reported an increase in the prevalence of carbapenemase-producing *E. coli* from 0% in 2011 to 1.9% in 2017.

The reported carbapenemases in *E. coli* primarily include *Klebsiella pneumoniae* carbapenemases (KPC), metallo-β-lactamases (MBL), including the VIM, IMP, GIM and NDM type, and oxacillin-hydrolyzing metallo-β-lactamases (OXA) [74]; however, different reports around the world have shown that the predominant types in *E. coli* are of the New Delhi metallo-β-lactamase (NDM-1) and carbapenem-hydrolyzing oxacillinase-48 (OXA-48) types [73, 75, 76].

#### *3.1.3.1 New Delhi metallo-β-lactamase*

The New Delhi metallo-β-lactamase (NDM-1) and closely related enzymes are a group of zinc-requiring metallo-β-lactamases capable of hydrolyzing a broad range of β-lactams including all penicillins, cephalosporins and carbapenems, just sparing monobactams, and are among the most recently identified carbapenemases. The

gene encoding these enzymes, *bla*NDM, has been identified on bacterial chromosomes and plasmids [77]; however, in the case of *E. coli*, *bla*NDM is mainly plasmid encoded with only few strains carrying it chromosomally [78].

NDM-1 was first identified in 2008 in India, a country that has been pointed out as the primary reservoir of NDM strains [77], followed by the Balkan states [79] and the Middle East [80]. From these three spots, *bla*NDM-1-carrying bacterial strains have spread around the world, mainly due to the ability of the carrying microorganisms to horizontally transfer the carbapenemase resistance trait via plasmids. An additional factor that has contributed to the worldwide dissemination of NDM-1-producing strains is the frequent co-existence of the *bla*NDM-1 gene on plasmids carrying additional antibiotic resistance genes, situation that has allowed the plasmid-carrying strains to thrive under environments of antibiotic selective pressure.

Since the first report of NDM-1, over 20 NDM variants have been reported; however, in *E. coli*, NDM-1, followed by NDM-5, are the predominant variants in human infections in different parts of the world [81, 82]. Surprisingly, in a study by Shen et al. [83] published in 2018, the highest prevalence in the human gut and livestock was of the NMD-5 variant, suggesting a possible shift from NDM-1 to NDM-5 in the community in China. An additional, and important finding of this study, was the identification, albeit small, of NDM-5 *E. coli* strains that co-express colistin resistance genes, *mcr-*1, in the gut of healthy individuals, situation that if not properly controlled might contribute to the future dissemination of *E. coli* strains that are resistant to last resource antibiotics.

#### *3.1.3.2 Carbapenem-hydrolyzing oxacillinase-48 (OXA-48)*

As with any other β-lactamase, OXA-48 hydrolyzes β-lactam antibiotics, including carbapenemases, but paradoxically spares broad-spectrum cephalosporins. OXA-48 genes were originally traced to the aquatic bacterium *Shewanella oneidensis*, but further studies now trace its origin to *Shewanella xiamenensis* [84]. Since the first description in Europe of OXA-48-carrying *Enterobacteriaceae*, several variants have been reported, including OXA-162, OXA-163, OXA-181, OXA-204, OXA-232, OXA244 and OXA-245.

Mainly found in *Klebsiella* species, reports on the detection of *bla*oxa-carrying *E. coli* have increased in the last 3 years in different parts of the world, being reported in studies in Myanmar [85], the United States [86] and Thailand [87]. In all three studies, the isolated strains were co-expressing *bla*OXA-48 or its variants and *bla*NDM5. Oxa-48-carrying *E. coli* strains have also been isolated in Europe, between January and October 2019, 134 cases of *E. coli* strains carrying the OXA-48 variant OXA-244 were isolated from clinical samples in Germany; this same variant was further identified in 119 *E. coli* strains isolated from other European countries [88]. The source and route of transmission of these strains is currently unclear.

As carbapenems are considering in many clinical instances as a last resource antibiotic, worldwide monitoring on the prevalence of *E. coli* carrying resistant traits against these agents should be continuously performed in order to prevent the spread of these strains, situation that can jeopardize even further the current antibiotic resistance crisis.

#### **4. Conclusions**

The ability of *Escherichia coli* to colonize the gut of humans and animals, thus facilitating its transmission via the fecal-oral route, and its ability to transmit and

**191**

**Author details**

Mario Galindo-Méndez

provided the original work is properly cited.

**Conflict of interest**

Laboratorios Galindo SC, Universidad Anáhuac Oaxaca, Oaxaca, Mexico

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: mgm@laboratoriosgalindo.com

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

uptake antibiotic resistance genes via plasmids to and from other bacteria have made this organism a key target in the fight against antimicrobial resistance. As discussed in this chapter, *E. coli* has evolved different mechanisms to fight off the action of antibiotics, and in many cases a single strain can carry resistance genes to

The emergence of antibiotic resistance has been shown to be multifactorial, but all elements coincide in a major topic: antibiotic over abuse, both in human and veterinary medicine. The establishment of antibiotic stewardship programs is a major necessity in all nations as a way to reduced antibiotic resistance. However, as the spread and maintenance of *E. coli*-resistant traits among humans and between animals and humans is driven by additional, and probably more difficult to tackle, social issues such as lack of hygiene, lack of drinking water and house overcrowding, these factors must be taken care of in order to truly impact antibiotic resistance.

distinct classes of these agents, thus complicating treatment.

The author declares no conflict of interest.

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

encoded with only few strains carrying it chromosomally [78].

strains that are resistant to last resource antibiotics.

*3.1.3.2 Carbapenem-hydrolyzing oxacillinase-48 (OXA-48)*

gene encoding these enzymes, *bla*NDM, has been identified on bacterial chromosomes and plasmids [77]; however, in the case of *E. coli*, *bla*NDM is mainly plasmid

NDM-1 was first identified in 2008 in India, a country that has been pointed out as the primary reservoir of NDM strains [77], followed by the Balkan states [79] and the Middle East [80]. From these three spots, *bla*NDM-1-carrying bacterial strains have spread around the world, mainly due to the ability of the carrying microorganisms to horizontally transfer the carbapenemase resistance trait via plasmids. An additional factor that has contributed to the worldwide dissemination of NDM-1-producing strains is the frequent co-existence of the *bla*NDM-1 gene on plasmids carrying additional antibiotic resistance genes, situation that has allowed the plasmid-carrying strains to thrive under environments of antibiotic selective

Since the first report of NDM-1, over 20 NDM variants have been reported; however, in *E. coli*, NDM-1, followed by NDM-5, are the predominant variants in human infections in different parts of the world [81, 82]. Surprisingly, in a study by Shen et al. [83] published in 2018, the highest prevalence in the human gut and livestock was of the NMD-5 variant, suggesting a possible shift from NDM-1 to NDM-5 in the community in China. An additional, and important finding of this study, was the identification, albeit small, of NDM-5 *E. coli* strains that co-express colistin resistance genes, *mcr-*1, in the gut of healthy individuals, situation that if not properly controlled might contribute to the future dissemination of *E. coli*

As with any other β-lactamase, OXA-48 hydrolyzes β-lactam antibiotics, including carbapenemases, but paradoxically spares broad-spectrum cephalosporins. OXA-48 genes were originally traced to the aquatic bacterium *Shewanella oneidensis*, but further studies now trace its origin to *Shewanella xiamenensis* [84]. Since the first description in Europe of OXA-48-carrying *Enterobacteriaceae*, several variants have been reported, including OXA-162, OXA-163, OXA-181, OXA-204, OXA-232,

Mainly found in *Klebsiella* species, reports on the detection of *bla*oxa-carrying *E. coli* have increased in the last 3 years in different parts of the world, being reported in studies in Myanmar [85], the United States [86] and Thailand [87]. In all three studies, the isolated strains were co-expressing *bla*OXA-48 or its variants and *bla*NDM5. Oxa-48-carrying *E. coli* strains have also been isolated in Europe, between January and October 2019, 134 cases of *E. coli* strains carrying the OXA-48 variant OXA-244 were isolated from clinical samples in Germany; this same variant was further identified in 119 *E. coli* strains isolated from other European countries [88]. The

As carbapenems are considering in many clinical instances as a last resource antibiotic, worldwide monitoring on the prevalence of *E. coli* carrying resistant traits against these agents should be continuously performed in order to prevent the spread of these strains, situation that can jeopardize even further the current

The ability of *Escherichia coli* to colonize the gut of humans and animals, thus facilitating its transmission via the fecal-oral route, and its ability to transmit and

source and route of transmission of these strains is currently unclear.

**190**

pressure.

OXA244 and OXA-245.

antibiotic resistance crisis.

**4. Conclusions**

uptake antibiotic resistance genes via plasmids to and from other bacteria have made this organism a key target in the fight against antimicrobial resistance. As discussed in this chapter, *E. coli* has evolved different mechanisms to fight off the action of antibiotics, and in many cases a single strain can carry resistance genes to distinct classes of these agents, thus complicating treatment.

The emergence of antibiotic resistance has been shown to be multifactorial, but all elements coincide in a major topic: antibiotic over abuse, both in human and veterinary medicine. The establishment of antibiotic stewardship programs is a major necessity in all nations as a way to reduced antibiotic resistance. However, as the spread and maintenance of *E. coli*-resistant traits among humans and between animals and humans is driven by additional, and probably more difficult to tackle, social issues such as lack of hygiene, lack of drinking water and house overcrowding, these factors must be taken care of in order to truly impact antibiotic resistance.

#### **Conflict of interest**

The author declares no conflict of interest.

#### **Author details**

Mario Galindo-Méndez Laboratorios Galindo SC, Universidad Anáhuac Oaxaca, Oaxaca, Mexico

\*Address all correspondence to: mgm@laboratoriosgalindo.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, et al. *Escherichia coli* K-12: A cooperatively developed annotation snapshot—2005. Nucleic Acids Research. 2006;**34**:1-9. DOI: 10.1093/nar/gkj405

[2] Hewitt JH, Rigby J. Effect of various milk feeds on numbers of *Escherichia coli* and *Bifidobacterium* in the stools of new-born infants. Journal of Hygiene (London). 1976;**77**(1):129-139. DOI: 10.1017/s0022172400055601

[3] Mohr K. History of antibiotics research. Current Topics in Microbiology and Immunology. 2016;**398**:237-272. DOI: 10.1007/ 82\_2016\_499

[4] Lowy FD. Antimicrobial resistance: The example of *Staphylococcus aureus*. The Journal of Clinical Investigation. 2003;**111**(9):1265-1273. DOI: 10.1172/ JCI18535

[5] World Health Organization. WHO Publishes List of Bacteria for Which New Antibiotics Are Urgently Needed. 2017. Available from: https://www.who. int/news-room/detail/27-02-2017-whopublishes-list-of-bacteria-for-whichnew-antibiotics-are-urgently-needed [Accessed: 09 April 2020]

[6] Tadesse DA, Zhao S, Tong E, Ayers S, Singh A, Bartholomew MJ. Antimicrobial drug resistance in *Escherichia coli* from humans and food animals, United States, 1950-2002. Emerging Infectious Diseases. 2012;**18**(5):741-749. DOI: 10.3201/ eid1805.111153

[7] Ny S, Edquist P, Dumpis U, Gröndahl-Yli-Hannuksela K, Hermes J, Kling AM, et al. Antimicrobial resistance of *Escherichia coli* isolates from outpatient urinary tract infections in women in six European countries including Russia. Journal of Global

Antimicrobial Resistance. 2019;**17**: 25-34. DOI: 10.1016/j.jgar.2018.11.004

[8] World Health Organization. WHO Report on Surveillance of Antibiotic Consumption. 2018. Available from: https://apps.who.int/iris/bitstream/han dle/10665/277359/9789241514880-eng. pdf [Accessed: 09 April 2020]

[9] Sommer MO, Dantas G, Church GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science. 2009;**325**(5944):1128-1131. DOI: 10.1126/science.1176950

[10] Cox G, Wright GD. Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions. International Journal of Medical Microbiology. 2013;**303**(6-7):287-292. DOI: 10.1016/j.ijmm.2013.02.009

[11] Liu A, Tran L, Becket E, Lee K, Chinn L, Park E, et al. Antibiotic sensitivity profiles determined with an *Escherichia coli* gene knockout collection: Generating an antibiotic bar code. Antimicrobial Agents and Chemotherapy. 2010;**54**:1393-1403. DOI: 10.1128/AAC.00906-09

[12] Nikaido H, Rosenberg EY, Foulds J. Porin channels in *Escherichia coli*: Studies with beta-lactams in intact cells. Journal of Bacteriology. 1983;**153**(1):232-240. DOI: 10.1128/ JB.153.1.232-240.1983

[13] European Centre for Disease Prevention and Control. Surveillance of Antimicrobial Resistance in Europe. 2018. Available from: https://www. ecdc.europa.eu/en/publications-data/ surveillance-antimicrobial-resistanceeurope-2018 [Accessed: 10 April 2020]

[14] Critchley I, Cotroneo N, Pucci M, Mendes R. The burden in antimicrobial resistance among urinary tract isolates

**193**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

in *Escherichia coli* in the United States in 2017. PLoS One. 2019;**14**(12):e0220265. DOI: 10.1371/journal.pone.0220265

consumption between 2000 and 2015. Proceedings of the National Academy of Sciences of the United States of America. 2018;**115**(15):E3463-E3470.

[22] Nordmann P, Poirel L. Epidemiology

2019;**69**(7):S521-S528. DOI: 10.1093/cid/

[23] Nordmann P, Poirel L. Strategies for identification of carbapenemaseproducing *Enterobacteriaceae*. The Journal of Antimicrobial Chemotherapy. 2013;**68**:487-489. DOI: 10.1093/jac/

[24] Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of inappropriate antibiotic prescribing in primary care clinics within a veterans affairs health care system. Antimicrobial Agents and Chemotherapy. 2018;**62**(8):e00337-18.

DOI: 10.1128/AAC.00337-18

[25] Zhang L, Levy K, Trueba G,

[26] McEwen SA, Fedorka-Cray PJ. Antimicrobial use and resistance in animals. Clinical Infectious Diseases. 2002;**34**(Suppl 3):S93-S106. DOI:

[27] Kaesbohrer A, Bakran-Lebl K, Irrgang A, Fischer J, Kämpf P,

[28] Galindo-Méndez M. Reservoirs of CTX-M extended spectrum

Schiffmann A. Diversity in prevalence and characteristics of ESBL/pAmpC producing *E. coli* in food in Germany. Veterinary Microbiology. 2019;**233**:52- 60. DOI: 10.1016/j.vetmic.2019.03.025

10.1086/340246

Cevallos W, Trostle J, Foxman B. Effects of selection pressure and genetic association on the relationship between antibiotic resistance and virulence in *Escherichia coli*. Antimicrobial Agents and Chemotherapy. 2015;**59**(11):6733- 6740. DOI: 10.1128/AAC.01094-15

DOI: 10.1073/pnas.1717295115

and diagnostics of carbapenem resistance in Gram-negative bacteria.

Clinical Infectious Diseases.

ciz824

dks426

[15] Garza-Gonzalez E, Morfın-Otero R,

Mendoza-Olazara S, Bocanegra-Ibarias S, Flores-Treviño S, Rodrıguez-

Noriega E, et al. A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period. PLoS One. 2019;**14**(3):e0209865. DOI: 10.1371/

[16] Huan Y, Oguto JO, Gu J, Ding F, You Y, Huo Y, et al. Comparative analysis of quinolone resistance in clinical isolates of *Klebsiella pneumoniae* and *Escherichia coli* from Chinese children and adults. BioMed Research International Journal. 2015;**168292**.

journal.pone.0209865

DOI: 10.1155/2015/168292

TurkHijyen.2018.68878

eou024

[17] Cöplü N, Simsek H, Gür D, Gözalan A, Hasdemir U, Gülay Z. The first results of national antimicrobial resistance surveillance system in Turkey. Türk Hijiyen ve Tecrübi Biyoloji Dergisi. 2018;**75**(4):333-344. DOI: 10.5505/

[18] Read AF, Woods RJ. Antibiotic resistance management. Evolution, Medicine, and Public Health.

[19] World Health Organization. Antimicrobial Resistance. Available from: https://www.who.int/healthtopics/antimicrobial-resistance [Accessed: 10 April 2020]

[20] Kolar M, Urbánek K, Látal T. Antibiotic selective pressure and development of bacterial resistance. International Journal of Antimicrobial Agents. 2001;**17**(5):357-363. DOI: 10.1016/s0924-8579(01)00317-x

[21] Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al. Global increase and geographic convergence in antibiotic

2014;**2014**(1):147. DOI: 10.1093/emph/

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

in *Escherichia coli* in the United States in 2017. PLoS One. 2019;**14**(12):e0220265. DOI: 10.1371/journal.pone.0220265

[15] Garza-Gonzalez E, Morfın-Otero R, Mendoza-Olazara S, Bocanegra-Ibarias S, Flores-Treviño S, Rodrıguez-Noriega E, et al. A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period. PLoS One. 2019;**14**(3):e0209865. DOI: 10.1371/ journal.pone.0209865

[16] Huan Y, Oguto JO, Gu J, Ding F, You Y, Huo Y, et al. Comparative analysis of quinolone resistance in clinical isolates of *Klebsiella pneumoniae* and *Escherichia coli* from Chinese children and adults. BioMed Research International Journal. 2015;**168292**. DOI: 10.1155/2015/168292

[17] Cöplü N, Simsek H, Gür D, Gözalan A, Hasdemir U, Gülay Z. The first results of national antimicrobial resistance surveillance system in Turkey. Türk Hijiyen ve Tecrübi Biyoloji Dergisi. 2018;**75**(4):333-344. DOI: 10.5505/ TurkHijyen.2018.68878

[18] Read AF, Woods RJ. Antibiotic resistance management. Evolution, Medicine, and Public Health. 2014;**2014**(1):147. DOI: 10.1093/emph/ eou024

[19] World Health Organization. Antimicrobial Resistance. Available from: https://www.who.int/healthtopics/antimicrobial-resistance [Accessed: 10 April 2020]

[20] Kolar M, Urbánek K, Látal T. Antibiotic selective pressure and development of bacterial resistance. International Journal of Antimicrobial Agents. 2001;**17**(5):357-363. DOI: 10.1016/s0924-8579(01)00317-x

[21] Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences of the United States of America. 2018;**115**(15):E3463-E3470. DOI: 10.1073/pnas.1717295115

[22] Nordmann P, Poirel L. Epidemiology and diagnostics of carbapenem resistance in Gram-negative bacteria. Clinical Infectious Diseases. 2019;**69**(7):S521-S528. DOI: 10.1093/cid/ ciz824

[23] Nordmann P, Poirel L. Strategies for identification of carbapenemaseproducing *Enterobacteriaceae*. The Journal of Antimicrobial Chemotherapy. 2013;**68**:487-489. DOI: 10.1093/jac/ dks426

[24] Shively NR, Buehrle DJ, Clancy CJ, Decker BK. Prevalence of inappropriate antibiotic prescribing in primary care clinics within a veterans affairs health care system. Antimicrobial Agents and Chemotherapy. 2018;**62**(8):e00337-18. DOI: 10.1128/AAC.00337-18

[25] Zhang L, Levy K, Trueba G, Cevallos W, Trostle J, Foxman B. Effects of selection pressure and genetic association on the relationship between antibiotic resistance and virulence in *Escherichia coli*. Antimicrobial Agents and Chemotherapy. 2015;**59**(11):6733- 6740. DOI: 10.1128/AAC.01094-15

[26] McEwen SA, Fedorka-Cray PJ. Antimicrobial use and resistance in animals. Clinical Infectious Diseases. 2002;**34**(Suppl 3):S93-S106. DOI: 10.1086/340246

[27] Kaesbohrer A, Bakran-Lebl K, Irrgang A, Fischer J, Kämpf P, Schiffmann A. Diversity in prevalence and characteristics of ESBL/pAmpC producing *E. coli* in food in Germany. Veterinary Microbiology. 2019;**233**:52- 60. DOI: 10.1016/j.vetmic.2019.03.025

[28] Galindo-Méndez M. Reservoirs of CTX-M extended spectrum

**192**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

Antimicrobial Resistance. 2019;**17**: 25-34. DOI: 10.1016/j.jgar.2018.11.004

pdf [Accessed: 09 April 2020]

10.1126/science.1176950

[10] Cox G, Wright GD. Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions. International Journal of Medical Microbiology. 2013;**303**(6-7):287-292. DOI: 10.1016/j.ijmm.2013.02.009

[11] Liu A, Tran L, Becket E, Lee K, Chinn L, Park E, et al. Antibiotic sensitivity profiles determined with an *Escherichia coli* gene knockout collection: Generating an antibiotic bar code. Antimicrobial Agents and Chemotherapy. 2010;**54**:1393-1403. DOI: 10.1128/AAC.00906-09

[12] Nikaido H, Rosenberg EY,

[13] European Centre for Disease Prevention and Control. Surveillance of Antimicrobial Resistance in Europe. 2018. Available from: https://www. ecdc.europa.eu/en/publications-data/ surveillance-antimicrobial-resistanceeurope-2018 [Accessed: 10 April 2020]

[14] Critchley I, Cotroneo N, Pucci M, Mendes R. The burden in antimicrobial resistance among urinary tract isolates

JB.153.1.232-240.1983

Foulds J. Porin channels in *Escherichia coli*: Studies with beta-lactams in intact cells. Journal of Bacteriology. 1983;**153**(1):232-240. DOI: 10.1128/

[8] World Health Organization. WHO Report on Surveillance of Antibiotic Consumption. 2018. Available from: https://apps.who.int/iris/bitstream/han dle/10665/277359/9789241514880-eng.

[9] Sommer MO, Dantas G, Church GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science. 2009;**325**(5944):1128-1131. DOI:

[1] Riley M, Abe T, Arnaud MB,

DOI: 10.1093/nar/gkj405

**References**

10.1017/s0022172400055601

82\_2016\_499

JCI18535

[3] Mohr K. History of antibiotics research. Current Topics in Microbiology and Immunology. 2016;**398**:237-272. DOI: 10.1007/

[4] Lowy FD. Antimicrobial resistance: The example of *Staphylococcus aureus*. The Journal of Clinical Investigation. 2003;**111**(9):1265-1273. DOI: 10.1172/

[5] World Health Organization. WHO Publishes List of Bacteria for Which New Antibiotics Are Urgently Needed. 2017. Available from: https://www.who. int/news-room/detail/27-02-2017-whopublishes-list-of-bacteria-for-whichnew-antibiotics-are-urgently-needed

[Accessed: 09 April 2020]

eid1805.111153

[6] Tadesse DA, Zhao S, Tong E, Ayers S, Singh A, Bartholomew MJ. Antimicrobial drug resistance in *Escherichia coli* from humans and food animals, United States, 1950-2002. Emerging Infectious Diseases. 2012;**18**(5):741-749. DOI: 10.3201/

[7] Ny S, Edquist P, Dumpis U, Gröndahl-Yli-Hannuksela K,

Hermes J, Kling AM, et al. Antimicrobial resistance of *Escherichia coli* isolates from outpatient urinary tract infections in women in six European countries including Russia. Journal of Global

Berlyn MK, Blattner FR, Chaudhuri RR, et al. *Escherichia coli* K-12: A cooperatively developed annotation snapshot—2005. Nucleic Acids Research. 2006;**34**:1-9.

[2] Hewitt JH, Rigby J. Effect of various milk feeds on numbers of *Escherichia coli* and *Bifidobacterium* in the stools of new-born infants. Journal of Hygiene (London). 1976;**77**(1):129-139. DOI:

β-lactamase-producing *Enterobacteriaceae* in Oaxaca, Mexico. Journal of Microbiology & Experimentation. 2019;**7**(1):43-47. DOI: 10.15406/jmen.2019.07.00239

[29] Köck R, Daniels-Haardt I, Becker K, Mellmann A, Friedrich AW, Mevius D. Carbapenemase-resistant *Enterobacteriaceae* in wildlife, foodproducing, and companion animals: A systematic review. Clinical Microbiology and Infection. 2018;**24**(12):1241-1250. DOI: 10.1016/j.cmi.2018.04.004

[30] Joshi PR, Thummeepak R, Leugtongkam U, Pooarlai R, Paudel S, Acharya M, et al. The emergence of colistin-resistant *Escherichia coli* in chicken meats in Nepal. FEMS Microbiology Letters. 2019;**366**(20):fnz237. DOI: 10.1093/ femsle/fnz237

[31] Ruppé E, Lixandru B, Cojocaru R, Buke C, Paramythiotou E, Angebault C, et al. Relative fecal abundance of extended-spectrumβ-lactamase-producing *Escherichia coli* strains and their occurrence in urinary tract infections in women. Antimicrobial Agents and Chemotherapy. 2013;**57**(9):4512-4517. DOI: 10.1128/AAC.00238-13

[32] Collignon P, Beggs JJ, Walsh TR, Gandra S, Laxminarayan R. Anthropological and socioeconomic factors contributing to global antimicrobial resistance: A univariate and multivariable analysis. The Lancet Planetary Health. 2018;**2**:e398-e405. DOI: 10.1016/S2542-5196(18)30186-4

[33] Hu Y, Yang X, Qin J, Lu N, Cheng G, Wu N. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nature Communications. 2013;**4**:2151. DOI: 10.1038/ncomms3151

[34] Canton R, Coque TM. The CTX-M β-lactamase pandemic. Current Opinion in Microbiology. 2006;**9**(5):466-475. DOI: 10.1016/j.mib.2006.08.011

[35] Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: The phantom menace. The Journal of Antimicrobial Chemotherapy. 2012;**67**(7):1597-1606. DOI: 10.1093/jac/ dks121

[36] von Wintersdorff CJH, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LV. Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Frontiers in Microbiology. 2016;**7**:173. DOI: 10.3389/ fmicb.2016.00173

[37] Ye Q, Wu Q, Zhang S, Zhang J, Yang G, Wang J, et al. Characterization of extended-Spectrum β-lactamaseproducing *Enterobacteriaceae* from retail food in China. Frontiers in Microbiology. 2018;**9**:1709. DOI: 10.3389/fmicb.2018.01709

[38] Prelog M, Grif K, Decristoforo C, Wurzner R, Kiechl-Kohlendorfer U, Brunner A, et al. Tetracycline-resistant *Escherichia coli* strains are inherited from parents and persist in the infant's intestines in the absence of selective pressure. European Journal of Pediatrics. 2009;**168**(10):1181-1187. DOI: 10.1007/s00431-008-0901-0

[39] Bryce A, Costelloe C, Hawcroft C, Wootton M, Hay AD. Faecal carriage of antibiotic resistant *Escherichia coli* in asymptomatic children and associations with primary care antibiotic prescribing: A systematic review and meta-analysis. BMC Infectious Diseases. 2016;**16**:359. DOI: 10.1186/ s12879-016-1697-6

[40] Bourrel AS, Poirel L, Royer G, Darty M, Vuillemin X, Kieffer N, et al. Colistin resistance in Parisian inpatient faecal *Escherichia coli* as the result of two distinct evolutionary pathways. The Journal of Antimicrobial Chemotherapy.

**195**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

2019;**74**(6):1521-1530. DOI: 10.1093/jac/

[47] Philippon A, Labia R, Jacoby G. Extended-spectrum beta-lactamases.

[48] Bonnet R. Growing group of extended-spectrum β-lactamases: The CTX-M enzymes. Antimicrobial Agents and Chemotherapy. 2004;**48**(1):1-14. DOI: 10.1128/AAC.48.1.1-14.2004

[49] Liahopoulus A, Mevius D, Ceccarelli D. A review of SHV extended-spectrum β-lactamases: Neglected yet ubiquitous. Frontiers in Microbiology. 2016;**7**:1374. DOI:

10.3389/fmicb.2016.01374

[50] Paterson DL, Bonomo RA. Extended-spectrum β-lactamases: A clinical update. Clinical Microbiology Reviews. 2005;**18**(4):657-686. DOI: 10.1128/CMR.18.4.657-686.2005

[51] Cantón R, Ruiz-Garbajosa P. Co-resistance: An opportunity for the bacteria and resistance genes. Current Opinion in Pharmacology. 2011;**11**:477- 485. DOI: 10.1016/j.coph.2011.07.007

[52] Boyd DA, Tyler S, Christianson S, McGeer A, Muller MP, Willey BM, et al. Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum betalactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrobial Agents and Chemotherapy. 2004;**48**(10):3758-3764. DOI: 10.1128/AAC.48.10.3758-3764.2004

[53] Ramadan A, Abdelaziz NA, Amin NA, Aziz RK. Novel *bla*CTX-M variants and genotype-phenotype correlations among clinical isolates of extended spectrum beta lactamaseproducing *Escherichia coli*. Scientific Reports. 2019;**9**(1):4224. DOI: 10.1038/

s41598-019-39730-0

[54] Bevan ER, Jones AM,

Hawkey PM. Global epidemiology of

Chemotherapy. 1989;**33**:1131-1136. DOI:

Antimicrobial Agents and

10.1128/aac.33.8.1131

Ranero A, Arzate-Barbosa P, Arias-de la Garza E, Méndez-Tenorio A, Murcia-Garzón J. First clinical isolate of *Escherichia coli* harboring mcr-1 gene in Mexico. PLoS One. 2019;**14**(4):e0214648. DOI: 10.1371/ journal.pone.0214648. eCollection 2019

[41] Merida-Vieyra J, De Colsa-

[42] Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A. Import

spectrum β-lactamase-producing *Enterobacteriaceae* by international travellers (COMBAT study): A prospective, multicentre cohort study. The Lancet Infectious Diseases. 2017;**17**(1):78-85. DOI: 10.1016/ S1473-3099(16)30319-X

[43] Valverde A, Grill F, Coque TM, Pintado V, Baquero F, Canton R, et al. High rate of intestinal colonization with extended spectrum-betalactamase-producing organisms in household contacts of infected community patients. Journal of Clinical Microbiology. 2008;**46**(8):2796-2799.

DOI: 10.1128/JCM.01008-08

[45] Bush K. Past and present perspectives on β-lactamases. Antimicrobial Agents and

DOI: 10.1128/AAC.01076-18

[46] Bush K, Jacoby G. Updated functional classification of β

DOI: 10.1128/AAC.01009-09

[44] Lee K, Kim DW, Lee DH, Kim YS, Bu JH, Cha JH. Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance. Microbiome. 2020;**8**(1):2. DOI: 10.1186/s40168-019-0774-7

Chemotherapy. 2018;**62**(10):e01076-18.

lactamases. Antimicrobial Agents and Chemotherapy. 2010;**54**(3):969-976.

and spread of extended-

dkz090

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

in Microbiology. 2006;**9**(5):466-475. DOI: 10.1016/j.mib.2006.08.011

[35] Poirel L, Potron A, Nordmann P. OXA-48-like carbapenemases: The phantom menace. The Journal of Antimicrobial Chemotherapy.

2012;**67**(7):1597-1606. DOI: 10.1093/jac/

[36] von Wintersdorff CJH, Penders J,

Dissemination of antimicrobial resistance

in microbial ecosystems through horizontal gene transfer. Frontiers in Microbiology. 2016;**7**:173. DOI: 10.3389/

[37] Ye Q, Wu Q, Zhang S, Zhang J, Yang G, Wang J, et al. Characterization of extended-Spectrum β-lactamaseproducing *Enterobacteriaceae* from retail food in China. Frontiers in Microbiology. 2018;**9**:1709. DOI: 10.3389/fmicb.2018.01709

[38] Prelog M, Grif K, Decristoforo C, Wurzner R, Kiechl-Kohlendorfer U, Brunner A, et al. Tetracycline-resistant *Escherichia coli* strains are inherited from parents and persist in the infant's intestines in the absence of selective pressure. European Journal of Pediatrics. 2009;**168**(10):1181-1187. DOI: 10.1007/s00431-008-0901-0

[39] Bryce A, Costelloe C, Hawcroft C, Wootton M, Hay AD. Faecal carriage of antibiotic resistant *Escherichia coli* in asymptomatic children and associations

with primary care antibiotic prescribing: A systematic review and meta-analysis. BMC Infectious Diseases. 2016;**16**:359. DOI: 10.1186/

[40] Bourrel AS, Poirel L, Royer G, Darty M, Vuillemin X, Kieffer N, et al. Colistin resistance in Parisian inpatient faecal *Escherichia coli* as the result of two distinct evolutionary pathways. The Journal of Antimicrobial Chemotherapy.

s12879-016-1697-6

van Niekerk JM, Mills ND, Majumder S, van Alphen LV.

fmicb.2016.00173

dks121

β-lactamase-producing *Enterobacteriaceae* in Oaxaca, Mexico. Journal of Microbiology & Experimentation. 2019;**7**(1):43-47. DOI: 10.15406/jmen.2019.07.00239

[29] Köck R, Daniels-Haardt I,

[30] Joshi PR, Thummeepak R, Leugtongkam U, Pooarlai R, Paudel S, Acharya M, et al. The emergence of colistin-resistant *Escherichia coli* in chicken meats in Nepal. FEMS Microbiology Letters. 2019;**366**(20):fnz237. DOI: 10.1093/

[31] Ruppé E, Lixandru B, Cojocaru R,

Buke C, Paramythiotou E, Angebault C, et al. Relative fecal abundance of extended-spectrumβ-lactamase-producing *Escherichia coli* strains and their occurrence in urinary tract infections in women. Antimicrobial Agents and Chemotherapy. 2013;**57**(9):4512-4517.

DOI: 10.1128/AAC.00238-13

Gandra S, Laxminarayan R.

10.1038/ncomms3151

[32] Collignon P, Beggs JJ, Walsh TR,

Anthropological and socioeconomic factors contributing to global

antimicrobial resistance: A univariate and multivariable analysis. The Lancet Planetary Health. 2018;**2**:e398-e405. DOI: 10.1016/S2542-5196(18)30186-4

[33] Hu Y, Yang X, Qin J, Lu N, Cheng G, Wu N. Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nature Communications. 2013;**4**:2151. DOI:

[34] Canton R, Coque TM. The CTX-M β-lactamase pandemic. Current Opinion

femsle/fnz237

Becker K, Mellmann A, Friedrich AW, Mevius D. Carbapenemase-resistant *Enterobacteriaceae* in wildlife, foodproducing, and companion animals: A systematic review. Clinical Microbiology and Infection. 2018;**24**(12):1241-1250. DOI: 10.1016/j.cmi.2018.04.004

**194**

2019;**74**(6):1521-1530. DOI: 10.1093/jac/ dkz090

[41] Merida-Vieyra J, De Colsa-Ranero A, Arzate-Barbosa P, Arias-de la Garza E, Méndez-Tenorio A, Murcia-Garzón J. First clinical isolate of *Escherichia coli* harboring mcr-1 gene in Mexico. PLoS One. 2019;**14**(4):e0214648. DOI: 10.1371/ journal.pone.0214648. eCollection 2019

[42] Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A. Import and spread of extendedspectrum β-lactamase-producing *Enterobacteriaceae* by international travellers (COMBAT study): A prospective, multicentre cohort study. The Lancet Infectious Diseases. 2017;**17**(1):78-85. DOI: 10.1016/ S1473-3099(16)30319-X

[43] Valverde A, Grill F, Coque TM, Pintado V, Baquero F, Canton R, et al. High rate of intestinal colonization with extended spectrum-betalactamase-producing organisms in household contacts of infected community patients. Journal of Clinical Microbiology. 2008;**46**(8):2796-2799. DOI: 10.1128/JCM.01008-08

[44] Lee K, Kim DW, Lee DH, Kim YS, Bu JH, Cha JH. Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance. Microbiome. 2020;**8**(1):2. DOI: 10.1186/s40168-019-0774-7

[45] Bush K. Past and present perspectives on β-lactamases. Antimicrobial Agents and Chemotherapy. 2018;**62**(10):e01076-18. DOI: 10.1128/AAC.01076-18

[46] Bush K, Jacoby G. Updated functional classification of β lactamases. Antimicrobial Agents and Chemotherapy. 2010;**54**(3):969-976. DOI: 10.1128/AAC.01009-09

[47] Philippon A, Labia R, Jacoby G. Extended-spectrum beta-lactamases. Antimicrobial Agents and Chemotherapy. 1989;**33**:1131-1136. DOI: 10.1128/aac.33.8.1131

[48] Bonnet R. Growing group of extended-spectrum β-lactamases: The CTX-M enzymes. Antimicrobial Agents and Chemotherapy. 2004;**48**(1):1-14. DOI: 10.1128/AAC.48.1.1-14.2004

[49] Liahopoulus A, Mevius D, Ceccarelli D. A review of SHV extended-spectrum β-lactamases: Neglected yet ubiquitous. Frontiers in Microbiology. 2016;**7**:1374. DOI: 10.3389/fmicb.2016.01374

[50] Paterson DL, Bonomo RA. Extended-spectrum β-lactamases: A clinical update. Clinical Microbiology Reviews. 2005;**18**(4):657-686. DOI: 10.1128/CMR.18.4.657-686.2005

[51] Cantón R, Ruiz-Garbajosa P. Co-resistance: An opportunity for the bacteria and resistance genes. Current Opinion in Pharmacology. 2011;**11**:477- 485. DOI: 10.1016/j.coph.2011.07.007

[52] Boyd DA, Tyler S, Christianson S, McGeer A, Muller MP, Willey BM, et al. Complete nucleotide sequence of a 92-kilobase plasmid harboring the CTX-M-15 extended-spectrum betalactamase involved in an outbreak in long-term-care facilities in Toronto, Canada. Antimicrobial Agents and Chemotherapy. 2004;**48**(10):3758-3764. DOI: 10.1128/AAC.48.10.3758-3764.2004

[53] Ramadan A, Abdelaziz NA, Amin NA, Aziz RK. Novel *bla*CTX-M variants and genotype-phenotype correlations among clinical isolates of extended spectrum beta lactamaseproducing *Escherichia coli*. Scientific Reports. 2019;**9**(1):4224. DOI: 10.1038/ s41598-019-39730-0

[54] Bevan ER, Jones AM, Hawkey PM. Global epidemiology of CTX-M β-lactamases: Temporal and geographical shifts in genotype. Journal of Antimicrobial Chemotherapy. 2017;**72**(8):2145-2155. DOI: 10.1093/jac/ dkx146

[55] Johnson JR, Menard M, Johnston B, Kuskowski MA, Nichol K, Zhanel GG. Epidemic clonal groups of *Escherichia coli* as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to 2004. Antimicrobial Agents and Chemotherapy. 2009;**53**:2733-2739. DOI: 10.1128/AAC.00297-09

[56] Rogers BA, Sidjabat HE, Paterson DL. *Escherichia coli* O25b-ST131: A pandemic, multiresistant, community-associated strain. The Journal of Antimicrobial Chemotherapy. 2011;**66**(1):1-14. DOI: 10.1093/jac/dkq415

[57] Nicolas-Chanoine MH, Bertrand X, Madec JY. *Escherichia coli* ST131, an intriguing clonal group. Clinical Microbiology Reviews. 2014;**27**(3):543-574. DOI: 10.1128/ CMR.00125-13

[58] Whitmer GR, Moorthy G, Arshad M. The pandemic *Escherichia coli* sequence type 131 strain is acquired even in the absence of antibiotic exposure. PLoS Pathogens. 2019;**15**(12):e1008162. DOI: 10.1371/journal.ppat.1008162

[59] Peirano G, Pitout JDD. Molecular epidemiology of *Escherichia coli* producing CTX-M β-lactamases: The worldwide emergence of clone ST131 O25:H4. International Journal of Antimicrobial Agents. 2010;**35**(4):316-321. DOI: 10.1016/j. ijantimicag.2009.11.003

[60] Beceiro A, Bou G. Class β-lactamases: An increasing problem worldwide. Reviews in Medical Microbiology. 2004;**15**(4):141-152. DOI: 10.1097/00013542-200410000-00003

[61] Caroff N, Espaze E, Gautreau D, Richet H, Reynaud A. Analysis of the effects of -42 and -32 *ampC* promoter mutations in clinical isolates of *Escherichia coli* hyperproducing *AmpC*. The Journal of Antimicrobial Chemotherapy. 2000;**45**(6):783-788. DOI: 10.1093/jac/45.6.783

[62] Jaurin B, Normark S. Insertion of IS2 creates a novel ampC promoter in *Escherichia coli*. Cell. 1983;**32**(3):809-816. DOI: 10.1016/0092-8674(83)90067-3

[63] Matsumura Y, Tanaka M, Yamamoto M, Nagao M, Machida K, Ito Y, et al. High prevalence of carbapenem resistance among plasmidmediated AmpC beta-lactamaseproducing *Klebsiella pneumoniae* during outbreaks in liver transplantation units. International Journal of Antimicrobial Agents. 2015;**45**(1):33-40. DOI: 10.1016/j.ijantimicag.2014.08.015

[64] Vounba P, Arsenault J, Bada-Alambédji R, Fairbrother JM. Antimicrobial resistance and potential pathogenicity of *Escherichia coli* isolates from healthy broilers in Québec, Canada. Microbial Drug Resistance. 2019;**25**(7):1111-1121. DOI: 10.1089/ mdr.2018.0403

[65] Sen K, Berglund T, Soares MA, Taheri M, Ma Y, Khalil L, et al. Antibiotic resistance of *E. coli* isolated from a constructed wetland dominated by a crow roost, with emphasis on ESBL and AmpC containing *E. coli*. Frontiers in Microbiology. 2019;**10**:1034. DOI: 10.3389/fmicb.2019.01034

[66] Nakayama T, Kumeda Y, Kawahara R, Yamamoto Y. Quantification and longterm carriage study of human extended spectrum/AmpC β-lactamase-producing *Escherichia coli* after international travel to Vietnam. Journal of Global Antimicrobial Resistance. 2019;**21**:229- 234. DOI: 10.1016/j.jgar.2019.11.001

**197**

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

[67] Oliveira C, Amador P, Prudencio C,

2019;**24**(9):1900123. DOI: 10.2807/1560-

[73] Tian X, Zheng X, Sun Y, Fang R, Zhang S, Zhang X, et al. Molecular mechanisms and epidemiology of carbapenem-resistant *Escherichia coli* isolated from Chinese patients during 2002-2017. Infection and Drug Resistance. 2020;**13**:501-512. DOI:

[74] Nordmann P, Naas T, Poirel L. Global spread of carbapenemaseproducing *Enterobacteriaceae*. Emerging Infectious Diseases. 2011;**17**:1791-1798.

[75] Gauthier L, Dortet L, Cotellon G, Creton E, Cuzon G, Ponties V, et al. Diversity of carbapenemase-producing *Escherichia coli* isolates in France in 2012-2013. Antimicrobial Agents and Chemotherapy. 2018;**62**(8):e00266-18.

[76] Nordmann P, Poirel L. The difficultto-control spread of carbapenemase producers among *Enterobacteriaceae* worldwide. Clinical Microbiology and Infection. 2014;**20**(9):821-830. DOI:

[77] Kumarasamy KK, Toleman MA,

Balakrishnan R, et al. Emergence of

mechanism in India, Pakistan and the UK: A molecular, biological and epidemiological study. The Lancet Infectious Diseases. 2010;**10**(9):597-602. DOI: 10.1016/S1473-3099(10)70143-2

[78] Shen P, Yi M, Fu Y, Ruan Z, Du X, Yu Y, et al. Detection of an *Escherichia coli* sequence type 167 strain with two tandem copies of blaNDM-1 in the chromosome. Journal of Clinical Microbiology. 2016;**551**(1):199-205.

DOI: 10.3201/eid1210.110655

DOI: 10.1128/AAC.00266-18

10.1111/1469-0691.12719

Walsh TR, Bagaria J, Butt F,

a new antibiotic resistance

DOI: 10.1128/JCM.01581-16

[79] Zarfel G, Hoenigl M, Würstl B. Emergence of carbapenem-resistant *Enterobacetriaceae* in Austria,

7917. ES.2019.24.9.1900123

10.2147/IDR.S232010

[68] Rizi KS, Mosavat A, Youssefi M, Jamehdar SA, Ghazyini K, Safdari H, et al. High prevalence of blaCMY AmpC Beta-lactamase in ESBL co-producing *Escherichia coli* and *Klebsiella* spp. clinical isolates in northeast of Iran. Journal of Global Antimicrobial Resistance. 2020;**S2213-7165**(20):30075-8. DOI: 10.1016/j.jgar.2020.03.011. [Published online ahead of print, 01 Apr 2020]

[69] Dirar M, Bilal N, Ibrahim ME, Hamid M. Resistance patterns and phenotypic detection of β-lactamase enzymes among *Enterobacteriaceae* isolates from referral hospitals in Khartoum State, Sudan. Cureus. 2020;**12**(3):e7260. DOI: 10.7759/

[70] Ghosh B, Mukherjee M. Emergence of co-production of plasmid mediated AmpC beta-lactamase and ESBL in cefoxitin-resistant uropathogenic *Escherichia coli*. European Journal of Clinical Microbiology & Infectious Diseases. 2016;**35**(9):1449-1454. DOI:

10.1007/s10096-016-2683-z

in tertiary care hospital in India. International Journal of Microbiology. 2019;**2019**:7019578.

DOI:10.1155/2019/7019578

[72] Brolund A, Lagerqvist N, Byfors S, Struelens MJ, Monnet DL, Albiger B, et al. Worsening epidemiological situation of carbapenemase-producing *Enterobacteriaceae* in Europe, assessment by national experts from 37 countries, July 2018. Journal of Euro Surveillance.

[71] Mirza S, Jadhav S, Misra RN, Das NK. Coexistence of β-lactamases in community-acquired infections

Tomaz CT, Tavarez-Ratado P, Fernander R. ESBL and AmpC β-lactamases in clinical strains of *Escherichia coli* from Serra da Estrela, Portugal. Medicina (Kaunas, Lithuania) 2019;**55**(6):pii: E272. DOI: 10.3390/

medicina55060272

cureus.7260

*Antimicrobial Resistance in* Escherichia coli *DOI: http://dx.doi.org/10.5772/intechopen.93115*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

[61] Caroff N, Espaze E, Gautreau D, Richet H, Reynaud A. Analysis of the effects of -42 and -32 *ampC* promoter mutations in clinical isolates of *Escherichia coli* hyperproducing *AmpC*. The Journal of Antimicrobial Chemotherapy. 2000;**45**(6):783-788.

DOI: 10.1093/jac/45.6.783

[62] Jaurin B, Normark S. Insertion of IS2 creates a novel ampC promoter in *Escherichia coli*. Cell. 1983;**32**(3):809-816. DOI: 10.1016/0092-8674(83)90067-3

[63] Matsumura Y, Tanaka M, Yamamoto M, Nagao M, Machida K, Ito Y, et al. High prevalence of

[64] Vounba P, Arsenault J,

mdr.2018.0403

Bada-Alambédji R, Fairbrother JM. Antimicrobial resistance and potential pathogenicity of *Escherichia coli* isolates from healthy broilers in Québec, Canada. Microbial Drug Resistance. 2019;**25**(7):1111-1121. DOI: 10.1089/

[65] Sen K, Berglund T, Soares MA, Taheri M, Ma Y, Khalil L, et al. Antibiotic resistance of *E. coli* isolated from a constructed wetland dominated by a crow roost, with emphasis on ESBL and AmpC containing *E. coli*. Frontiers in Microbiology. 2019;**10**:1034. DOI:

[66] Nakayama T, Kumeda Y, Kawahara R, Yamamoto Y. Quantification and longterm carriage study of human extended spectrum/AmpC β-lactamase-producing *Escherichia coli* after international travel to Vietnam. Journal of Global Antimicrobial Resistance. 2019;**21**:229- 234. DOI: 10.1016/j.jgar.2019.11.001

10.3389/fmicb.2019.01034

carbapenem resistance among plasmidmediated AmpC beta-lactamaseproducing *Klebsiella pneumoniae* during outbreaks in liver transplantation units. International Journal of Antimicrobial Agents. 2015;**45**(1):33-40. DOI: 10.1016/j.ijantimicag.2014.08.015

CTX-M β-lactamases: Temporal and geographical shifts in genotype. Journal of Antimicrobial Chemotherapy. 2017;**72**(8):2145-2155. DOI: 10.1093/jac/

Johnston B, Kuskowski MA, Nichol K, Zhanel GG. Epidemic clonal groups of *Escherichia coli* as a cause of antimicrobial-resistant urinary tract infections in Canada, 2002 to 2004. Antimicrobial Agents and

Chemotherapy. 2009;**53**:2733-2739. DOI:

multiresistant, community-associated strain. The Journal of Antimicrobial Chemotherapy. 2011;**66**(1):1-14. DOI:

Bertrand X, Madec JY. *Escherichia coli* ST131, an intriguing clonal group. Clinical Microbiology Reviews. 2014;**27**(3):543-574. DOI: 10.1128/

[55] Johnson JR, Menard M,

10.1128/AAC.00297-09

10.1093/jac/dkq415

CMR.00125-13

[56] Rogers BA, Sidjabat HE, Paterson DL. *Escherichia coli* O25b-ST131: A pandemic,

[57] Nicolas-Chanoine MH,

[58] Whitmer GR, Moorthy G,

Arshad M. The pandemic *Escherichia coli* sequence type 131 strain is acquired even in the absence of antibiotic exposure. PLoS Pathogens. 2019;**15**(12):e1008162. DOI: 10.1371/journal.ppat.1008162

[59] Peirano G, Pitout JDD. Molecular epidemiology of *Escherichia coli* producing CTX-M β-lactamases: The worldwide emergence of clone ST131 O25:H4. International Journal of Antimicrobial Agents. 2010;**35**(4):316-321. DOI: 10.1016/j.

ijantimicag.2009.11.003

[60] Beceiro A, Bou G. Class

β-lactamases: An increasing problem worldwide. Reviews in Medical

Microbiology. 2004;**15**(4):141-152. DOI: 10.1097/00013542-200410000-00003

dkx146

**196**

[67] Oliveira C, Amador P, Prudencio C, Tomaz CT, Tavarez-Ratado P, Fernander R. ESBL and AmpC β-lactamases in clinical strains of *Escherichia coli* from Serra da Estrela, Portugal. Medicina (Kaunas, Lithuania) 2019;**55**(6):pii: E272. DOI: 10.3390/ medicina55060272

[68] Rizi KS, Mosavat A, Youssefi M, Jamehdar SA, Ghazyini K, Safdari H, et al. High prevalence of blaCMY AmpC Beta-lactamase in ESBL co-producing *Escherichia coli* and *Klebsiella* spp. clinical isolates in northeast of Iran. Journal of Global Antimicrobial Resistance. 2020;**S2213-7165**(20):30075-8. DOI: 10.1016/j.jgar.2020.03.011. [Published online ahead of print, 01 Apr 2020]

[69] Dirar M, Bilal N, Ibrahim ME, Hamid M. Resistance patterns and phenotypic detection of β-lactamase enzymes among *Enterobacteriaceae* isolates from referral hospitals in Khartoum State, Sudan. Cureus. 2020;**12**(3):e7260. DOI: 10.7759/ cureus.7260

[70] Ghosh B, Mukherjee M. Emergence of co-production of plasmid mediated AmpC beta-lactamase and ESBL in cefoxitin-resistant uropathogenic *Escherichia coli*. European Journal of Clinical Microbiology & Infectious Diseases. 2016;**35**(9):1449-1454. DOI: 10.1007/s10096-016-2683-z

[71] Mirza S, Jadhav S, Misra RN, Das NK. Coexistence of β-lactamases in community-acquired infections in tertiary care hospital in India. International Journal of Microbiology. 2019;**2019**:7019578. DOI:10.1155/2019/7019578

[72] Brolund A, Lagerqvist N, Byfors S, Struelens MJ, Monnet DL, Albiger B, et al. Worsening epidemiological situation of carbapenemase-producing *Enterobacteriaceae* in Europe, assessment by national experts from 37 countries, July 2018. Journal of Euro Surveillance.

2019;**24**(9):1900123. DOI: 10.2807/1560- 7917. ES.2019.24.9.1900123

[73] Tian X, Zheng X, Sun Y, Fang R, Zhang S, Zhang X, et al. Molecular mechanisms and epidemiology of carbapenem-resistant *Escherichia coli* isolated from Chinese patients during 2002-2017. Infection and Drug Resistance. 2020;**13**:501-512. DOI: 10.2147/IDR.S232010

[74] Nordmann P, Naas T, Poirel L. Global spread of carbapenemaseproducing *Enterobacteriaceae*. Emerging Infectious Diseases. 2011;**17**:1791-1798. DOI: 10.3201/eid1210.110655

[75] Gauthier L, Dortet L, Cotellon G, Creton E, Cuzon G, Ponties V, et al. Diversity of carbapenemase-producing *Escherichia coli* isolates in France in 2012-2013. Antimicrobial Agents and Chemotherapy. 2018;**62**(8):e00266-18. DOI: 10.1128/AAC.00266-18

[76] Nordmann P, Poirel L. The difficultto-control spread of carbapenemase producers among *Enterobacteriaceae* worldwide. Clinical Microbiology and Infection. 2014;**20**(9):821-830. DOI: 10.1111/1469-0691.12719

[77] Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan and the UK: A molecular, biological and epidemiological study. The Lancet Infectious Diseases. 2010;**10**(9):597-602. DOI: 10.1016/S1473-3099(10)70143-2

[78] Shen P, Yi M, Fu Y, Ruan Z, Du X, Yu Y, et al. Detection of an *Escherichia coli* sequence type 167 strain with two tandem copies of blaNDM-1 in the chromosome. Journal of Clinical Microbiology. 2016;**551**(1):199-205. DOI: 10.1128/JCM.01581-16

[79] Zarfel G, Hoenigl M, Würstl B. Emergence of carbapenem-resistant *Enterobacetriaceae* in Austria,

2001-2010. Clinical Microbiology and Infection. 2011;**17**(11):E5-E8. DOI: 10.1111/j.1469-0691.2011.03659.x

[80] Shibl A, Al-Agamy M, Memish Z, Senok A, Khader SA, Assiri A. The emergence of OXA-48 and NDM-1 positive *Klebsiella pneumonia* in Riyadh, Saudi Arabia. The Journal of Infectious Diseases. 2013;**17**(12):e1130-e1133. DOI: 10.1016/j.ijid.2013.06.016

[81] Ranjan A, Shaik S, Mondal A, Nandanwar N, Hussain A, Semmler T, et al. Molecular epidemiology and genome dynamics of New Delhi metallo-betalactamase-producing extraintestinal pathogenic *Escherichia coli* strains from India. Antimicrobial Agents and Chemotherapy. 2016;**60**(11):6795-6805. DOI: 10.1128/AAC.01345-16

[82] Hu X, Xu X, Wang X, Xue W, Zhou H, Zhang L, et al. Diversity of New Delhi metallo-beta-lactamaseproducing bacteria in China. International Journal of Infectious Diseases. 2017;**55**:92-95. DOI: 10.1016/j. ijid.2017.01.011

[83] Shen Z, Hu Y, Sun Q, Hu F, Zhou H, Shu L, et al. Emerging carriage of NDM-5 and MCR-1 in *Escherichia coli* from healthy people in multiple regions in China: A cross sectional observational study. EClinicalMedicine. 2018;**6**:11-20. DOI: 10.1016/j.eclinm.2018.11.003

[84] Potron A, Poirel L, Nordmann P. Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in *Shewanella xiamenensis*. Antimicrobial Agents and Chemotherapy. 2011;**55**(9):4405-4407. DOI: 10.1128/AAC.00681-11

[85] Aung MS, San N, Maw WW, San T, Urushibara N, Kawaguchiva M, et al. Prevalence of extended-spectrum betalactamase and carbapenemase genes in clinical isolates of *Escherichia coli* in Myanmar: Dominance of blaNMD5 and

emergence of blaOXA-181. Microbial Drug Resistance. 2018;**24**(9):1333-1344. DOI: 10.1089/mdr.2017.0387

[86] Hasassri ME, Boyce TG, Norgan SA, Cunningham PR, Jeraldo S, Weissman S, et al. An immunocompromised child with bloodstream infection caused by two *Escherichia coli* strains, one harboring NDM-5 and the other harboring OXA-48-like carbapenemase. Antimicrobial Agents and Chemotherapy. 2016;**60**:3270-3275. DOI: 10.1128/AAC.03118-15

[87] Lunha K, Chanawong A, Lulitanond C, Wilailuckana N, Charoensri L, Wonglakorn P. High level carbapenem-resistant OXA-48-producing *Klebsiella pneumoniae* with a novel OmpK36 variant and low-level, carbapenem-resistant, nonporin-deficient, OXA-181-producing *Escherichia coli* from Thailand. Diagnostic Microbiology and Infectious Disease. 2016;**85**:221-226. DOI: 10.1016/j.diagmicrobio.2016.03.009

[88] European Centre for Disease Prevention and Control. Increase in OXA-244-Producing *Escherichia coli* in the European Union/European Economic Area and the UK since 2013. 2020. Available from: https:// www.ecdc.europa.eu/sites/default/ files/documents/RRA-E-coli-OXA-244-producing-E-coli-EU-EEA-UKsince-2013.pdf [Accessed: 15 April 2020]

**199**

*aac(3)-II* and *aac(3)-IV*.

**Chapter 10**

**Abstract**

Antibiotic Resistance among Iraqi

*Escherichia coli* is a famous Gram-negative bacillary bacterium that belongs to Enterobacteriaceae. It is either micro-biota innocent for human or pathogenic with arrays of diseases. The pathogenic *E. coli* can be assigned to intestinal (InPEC) or extraintestinal (ExPEC) with disease ranging from watery diarrhea to pulmonary distress. The most prevalent form of InPEC is enteropathogenic *E. coli* (EPEC), while the most prevalent ExPEC is uropathogenic *E. coli* (UPEC). The other InPEC includes Shiga toxin–producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), diffusely adherent (DAEC) and adherent invasive *E. coli* (AIEC). ExPEC was implicated in cystitis, pyelonephritis, sepsis, respiratory tract infection, cervicovaginal infection (CVEC), meningitis (NMEC), otitis media, cholecystitis and wound infection. Antibiotic resistance is the challenging in world nowadays. Multidrug-resistant (MDR) *Escherichia coli* has become challenging with existing antibiotic options. *E. coli* pathogens have various virulence factors that determine their pathogenesis and antimicrobial resistance mechanisms. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance. The most commonly used antibiotic classes for InPEC and ExPEC were third-generation cephalosporin, carbapenem, fluoroquinolone and aminoglycosides. Actually, the most effective prescribed medication is one of the following: cefotaxime, ceftriaxone, ciprofloxacin, amikacin, gentamycin, levofloxacin and imipenem. Generally, according to our review for more than 100 local Iraqi studies among Iraqi provinces, the results revealed the resistance rate from highest to lowest as follows: cefotaxime (76.5%), ceftriaxone (75.9%), gentamycin (41.65%), ciprofloxacin (32.13%), amikacin (17.3%), levofloxacin (15%) and imipenem (5.14%). The resistance mechanisms may include genes encoding antibiotic-modifying enzymes like those of extended-spectrum beta-lactamases gene comprising: *blaCTX-M*, *blaTEM*, *blaSHV*, *blaOXA*, *blaPER*, *blaVIM*, *blaIMP*, *blaNDM* and *blaAMPc.* Efflux pumping includes AcrAB, while resistance to quinolone may be mediated by mutation among qnrA, qnrB, qnrD and qnrS. Resistance to aminoglycosides includes encoding to aminoglycosidemodifying enzymes like *aac(6)-Ib*, *aph(3)-I*, *aph(3)-IIa*, *aph(3)-Ib*, *ant(3)-I*,

**Keywords:** InPEC, ExPEC, CVEC, NMEC, DEC, *blaCTX-M*, *blaTEM*, *blaSHV*

*Hussein O.M. Al-Dahmoshi, Noor S.K. Al-Khafaji* 

Local *E. coli* Isolates

*and Mohammed H.O. Al-Allak*

#### **Chapter 10**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

emergence of blaOXA-181. Microbial Drug Resistance. 2018;**24**(9):1333-1344. DOI:

[86] Hasassri ME, Boyce TG, Norgan SA, Cunningham PR, Jeraldo S, Weissman S, et al. An immunocompromised child with bloodstream infection caused by two *Escherichia coli* strains, one harboring NDM-5 and the other harboring OXA-48-like

carbapenemase. Antimicrobial Agents and Chemotherapy. 2016;**60**:3270-3275.

Diagnostic Microbiology and Infectious

Disease. 2016;**85**:221-226. DOI: 10.1016/j.diagmicrobio.2016.03.009

[88] European Centre for Disease Prevention and Control. Increase in OXA-244-Producing *Escherichia coli* in the European Union/European Economic Area and the UK since 2013. 2020. Available from: https:// www.ecdc.europa.eu/sites/default/ files/documents/RRA-E-coli-OXA-244-producing-E-coli-EU-EEA-UKsince-2013.pdf [Accessed: 15 April

2020]

DOI: 10.1128/AAC.03118-15

[87] Lunha K, Chanawong A, Lulitanond C, Wilailuckana N, Charoensri L, Wonglakorn P. High level carbapenem-resistant OXA-48-producing *Klebsiella pneumoniae* with a novel OmpK36 variant and low-level, carbapenem-resistant, nonporin-deficient, OXA-181-producing *Escherichia coli* from Thailand.

10.1089/mdr.2017.0387

2001-2010. Clinical Microbiology and Infection. 2011;**17**(11):E5-E8. DOI: 10.1111/j.1469-0691.2011.03659.x

[80] Shibl A, Al-Agamy M, Memish Z, Senok A, Khader SA, Assiri A. The emergence of OXA-48 and NDM-1 positive *Klebsiella pneumonia* in Riyadh, Saudi Arabia. The Journal of Infectious Diseases. 2013;**17**(12):e1130-e1133. DOI:

10.1016/j.ijid.2013.06.016

of New Delhi metallo-beta-

DOI: 10.1128/AAC.01345-16

ijid.2017.01.011

[82] Hu X, Xu X, Wang X, Xue W, Zhou H, Zhang L, et al. Diversity of New Delhi metallo-beta-lactamaseproducing bacteria in China. International Journal of Infectious Diseases. 2017;**55**:92-95. DOI: 10.1016/j.

[83] Shen Z, Hu Y, Sun Q, Hu F,

Zhou H, Shu L, et al. Emerging carriage of NDM-5 and MCR-1 in *Escherichia coli* from healthy people in multiple regions in China: A cross sectional observational study. EClinicalMedicine. 2018;**6**:11-20. DOI: 10.1016/j.eclinm.2018.11.003

[84] Potron A, Poirel L, Nordmann P. Origin of OXA-181, an emerging carbapenem-hydrolyzing oxacillinase, as a chromosomal gene in *Shewanella xiamenensis*. Antimicrobial Agents and Chemotherapy. 2011;**55**(9):4405-4407.

[85] Aung MS, San N, Maw WW, San T, Urushibara N, Kawaguchiva M, et al. Prevalence of extended-spectrum betalactamase and carbapenemase genes in clinical isolates of *Escherichia coli* in Myanmar: Dominance of blaNMD5 and

DOI: 10.1128/AAC.00681-11

[81] Ranjan A, Shaik S, Mondal A, Nandanwar N, Hussain A, Semmler T, et al. Molecular

epidemiology and genome dynamics

lactamase-producing extraintestinal pathogenic *Escherichia coli* strains from India. Antimicrobial Agents and Chemotherapy. 2016;**60**(11):6795-6805.

**198**

## Antibiotic Resistance among Iraqi Local *E. coli* Isolates

*Hussein O.M. Al-Dahmoshi, Noor S.K. Al-Khafaji and Mohammed H.O. Al-Allak*

#### **Abstract**

*Escherichia coli* is a famous Gram-negative bacillary bacterium that belongs to Enterobacteriaceae. It is either micro-biota innocent for human or pathogenic with arrays of diseases. The pathogenic *E. coli* can be assigned to intestinal (InPEC) or extraintestinal (ExPEC) with disease ranging from watery diarrhea to pulmonary distress. The most prevalent form of InPEC is enteropathogenic *E. coli* (EPEC), while the most prevalent ExPEC is uropathogenic *E. coli* (UPEC). The other InPEC includes Shiga toxin–producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), diffusely adherent (DAEC) and adherent invasive *E. coli* (AIEC). ExPEC was implicated in cystitis, pyelonephritis, sepsis, respiratory tract infection, cervicovaginal infection (CVEC), meningitis (NMEC), otitis media, cholecystitis and wound infection. Antibiotic resistance is the challenging in world nowadays. Multidrug-resistant (MDR) *Escherichia coli* has become challenging with existing antibiotic options. *E. coli* pathogens have various virulence factors that determine their pathogenesis and antimicrobial resistance mechanisms. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance. The most commonly used antibiotic classes for InPEC and ExPEC were third-generation cephalosporin, carbapenem, fluoroquinolone and aminoglycosides. Actually, the most effective prescribed medication is one of the following: cefotaxime, ceftriaxone, ciprofloxacin, amikacin, gentamycin, levofloxacin and imipenem. Generally, according to our review for more than 100 local Iraqi studies among Iraqi provinces, the results revealed the resistance rate from highest to lowest as follows: cefotaxime (76.5%), ceftriaxone (75.9%), gentamycin (41.65%), ciprofloxacin (32.13%), amikacin (17.3%), levofloxacin (15%) and imipenem (5.14%). The resistance mechanisms may include genes encoding antibiotic-modifying enzymes like those of extended-spectrum beta-lactamases gene comprising: *blaCTX-M*, *blaTEM*, *blaSHV*, *blaOXA*, *blaPER*, *blaVIM*, *blaIMP*, *blaNDM* and *blaAMPc.* Efflux pumping includes AcrAB, while resistance to quinolone may be mediated by mutation among qnrA, qnrB, qnrD and qnrS. Resistance to aminoglycosides includes encoding to aminoglycosidemodifying enzymes like *aac(6)-Ib*, *aph(3)-I*, *aph(3)-IIa*, *aph(3)-Ib*, *ant(3)-I*, *aac(3)-II* and *aac(3)-IV*.

**Keywords:** InPEC, ExPEC, CVEC, NMEC, DEC, *blaCTX-M*, *blaTEM*, *blaSHV*

#### **1. Introduction**

*Escherichia coli* is prominent Gammaproteobacteria, Gram-negative bacilli live facultatively. It is the principal non-pathogenic facultative flora of the human intestine with harmless effect in healthy individuals. The virulent pathotypes of *E. coli* strains have the capability to cause a collection of intestinal and extraintestinal diseases, especially in immune-compromised persons [1]. Intestinal disease includes diarrhea or dysentery caused by six pathotypes, while extraintestinal diseases consists of vaginosis, urinary tract infections, respiratory tract infection, otitis media and meningitis [2, 3]. The enteropathogenic or diarrheagenic *E. coli* is an imperative cause of diarrhea in the newborn, immunocompromised and travelers. It can be assigned to one of the seven pathotypes: enteropathogenic (EPEC), Shiga toxin–producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), diffusely adherent (DAEC) and adherent invasive *E. coli* (AIEC) [4–6].

Uropathogenic *Escherichia coli* (UPEC) strains are the most significant causative agents of UTIs in humans. The total prevalence of UTIs caused by the UPEC strains is about 30–70% [7]. UPEC is the most common cause of community- and hospitalacquired urinary tract infections (UTIs). Isolates from uncomplicated communityacquired UTIs express a variety of virulence traits that promote the efficient colonization of the urinary tract. In contrast, nosocomial UTIs can be caused by *E. coli* strains that differ in their virulence traits from the community-acquired UTI isolates. UPEC virulence markers are used to distinguish these facultative extraintestinal pathogens, which belong to the intestinal flora of many healthy individuals, from intestinal pathogenic *E. coli* (IPEC) [8, 9].

One of the important extraintestinal *E. coli* (ExPEC) infections is nosocomial ventilator-associated pneumonia (VAP) with the mortality rate reaching 13%. Until the early 2000s, the ExPEC was not considered as a major pathogen responsible for ventilator-assisted pneumonia that may be due to focusing on other bacteria like *Staphylococcus aureus*, *Acinetobacter baumannii* and *Pseudomonas aeruginosa* [10–12]. Many studies stated the high frequency of ExPEC among VAP even more than *Staphylococcus aureus* and *Pseudomonas aeruginosa*. In developing countries, both hospital- and community-acquired respiratory tract infections (RTIs) are linked with emerging MDR *E. coli* [13–15].

*Escherichia coli* is most commonly associated with bloodstream infections and death due to sepsis. Sepsis is a life-threatening clinical condition affecting more than 40 million worldwide with mortality rate more than 15%. The incidence of sepsis caused by Gram-negative bacteria, such as *Escherichia coli* (*E. coli*), has been steadily increasing since the late 1990s. It ranks as the leading cause of death in intensive care units. *E. coli* accounts for approximately 14.1% of early onset neonatal sepsis and it is the second most common pathogen, along with coagulase negative Staphylococcus, after group B Streptococcus (GBS)2 [16–18].

*Escherichia coli* (especially K1) is one of the most common causative pathogens of neonatal meningitis, but the presence of *E coli* in an immunocompetent adult, causing meningitis, is rare with an annual incidence of less than one case per year. The penetration of *E. coli* through the blood-brain barrier is a key step of the meningitis pathogenesis. Diabetes mellitus, alcoholism, cirrhosis, HIV infection and malignancies are some of the risk factors to develop *E coli* meningitis. A distant source is usually identified, either from the urinary or the digestive tract [19–22].

According to the World Health Organization, *Enterobacteriaceae*, including *Escherichia coli*, are among the critical priority antibiotic-resistant bacteria. Multidrug-resistant (MDR) *Escherichia coli* has been listed as a priority pathogen by the World Health Organization (WHO) due to emerging antimicrobial resistance (AMR) [23, 24].

**201**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

**2.** *Escherichia coli* **diseases and antibiotic resistance**

**2.1 ExPEC-associated cystitis and antibiotic resistance**

in **Table 1**. The resistance genes are listed in **Table 2**.

**study**

**Antibiotic No. of isolate/**

*E. coli* (ExPEC) [25]. The most important diseases are as follows:

*E. coli* causes a wide range of diseases that can be assigned to either intestinal caused by intestinal *E. coli* (InPEC) or extraintestinal caused by extraintestinal

Cystitis is a common and expensive condition that impacts humans of different age groups from the neonate till geriatric age group. It is a pathogenic inflammation of the lower urinary tract. Women are more commonly afflicted with UTIs, and they are caused by common pathogens such as *Escherichia coli* (86%) [26]. Uropathogenic *Escherichia coli* (UPEC) is significantly associated with cystitis via sets of virulence factors (adhesins, siderophores, toxins, capsule production and protease) that assist its colonization, invasion, and survival within the host urinary system [27, 28]. High recurrence rates and increasing antimicrobial resistance among UPEC threaten to greatly increase the economic burden of these UTIs [5]. The resistance rate of Iraqi local UPEC to different antibiotic classes is summarized

The average resistance rate is as follows: cefotaxime (77%), ceftriaxone (70%), ciprofloxacin (45.47%), amikacin (23.42%), gentamycin (45.69%) and imipenem (6.06%). Resistance to beta-lactams was attributed to many mechanisms, and one of them is to the modifying enzymes especially *blaTEM*, *blaSHV*, *blaCTX-M*, *blaOXA*, *blaPER* and *blaVIM*, while resistance to ciprofloxacin was interpreted

Cefotaxime 246 85.13 Babylon [34, 40–43]

Ceftriaxone 176 81.21 Babylon [34, 40, 41, 43]

**Resistance % Province Reference**

 88.9 Najaf [30] 76.9 Karbala [44] 75.8 Wasit [36] 82.5 Saladin [45] 89.15 Erbil [46] 52 Zakho [47] 70 Kirkuk [48] 70.8 Duhok [49, 50] 78 Sulemania [51]

 100 Karbala [44] 75 Missan [31] 74.7 Wasit [36] 73.15 Anbar [33] 52 Erbil [46] 70 Zakho [47] 67 Kirkuk [48] 71.3 Duhok [49, 50] 34.5 Sulemania [51]

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

from intestinal pathogenic *E. coli* (IPEC) [8, 9].

with emerging MDR *E. coli* [13–15].

*Escherichia coli* is prominent Gammaproteobacteria, Gram-negative bacilli live facultatively. It is the principal non-pathogenic facultative flora of the human intestine with harmless effect in healthy individuals. The virulent pathotypes of *E. coli* strains have the capability to cause a collection of intestinal and extraintestinal diseases, especially in immune-compromised persons [1]. Intestinal disease includes diarrhea or dysentery caused by six pathotypes, while extraintestinal diseases consists of vaginosis, urinary tract infections, respiratory tract infection, otitis media and meningitis [2, 3]. The enteropathogenic or diarrheagenic *E. coli* is an imperative cause of diarrhea in the newborn, immunocompromised and travelers. It can be assigned to one of the seven pathotypes: enteropathogenic (EPEC), Shiga toxin–producing (STEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enteroinvasive (EIEC), diffusely adherent (DAEC) and adherent invasive *E. coli* (AIEC) [4–6].

Uropathogenic *Escherichia coli* (UPEC) strains are the most significant causative agents of UTIs in humans. The total prevalence of UTIs caused by the UPEC strains is about 30–70% [7]. UPEC is the most common cause of community- and hospitalacquired urinary tract infections (UTIs). Isolates from uncomplicated communityacquired UTIs express a variety of virulence traits that promote the efficient colonization of the urinary tract. In contrast, nosocomial UTIs can be caused by *E. coli* strains that differ in their virulence traits from the community-acquired UTI isolates. UPEC virulence markers are used to distinguish these facultative extraintestinal pathogens, which belong to the intestinal flora of many healthy individuals,

One of the important extraintestinal *E. coli* (ExPEC) infections is nosocomial ventilator-associated pneumonia (VAP) with the mortality rate reaching 13%. Until the early 2000s, the ExPEC was not considered as a major pathogen responsible for ventilator-assisted pneumonia that may be due to focusing on other bacteria like *Staphylococcus aureus*, *Acinetobacter baumannii* and *Pseudomonas aeruginosa* [10–12]. Many studies stated the high frequency of ExPEC among VAP even more than *Staphylococcus aureus* and *Pseudomonas aeruginosa*. In developing countries, both hospital- and community-acquired respiratory tract infections (RTIs) are linked

*Escherichia coli* is most commonly associated with bloodstream infections and death due to sepsis. Sepsis is a life-threatening clinical condition affecting more than 40 million worldwide with mortality rate more than 15%. The incidence of sepsis caused by Gram-negative bacteria, such as *Escherichia coli* (*E. coli*), has been steadily increasing since the late 1990s. It ranks as the leading cause of death in intensive care units. *E. coli* accounts for approximately 14.1% of early onset neonatal sepsis and it is the second most common pathogen, along with coagulase negative

*Escherichia coli* (especially K1) is one of the most common causative pathogens of neonatal meningitis, but the presence of *E coli* in an immunocompetent adult, causing meningitis, is rare with an annual incidence of less than one case per year. The penetration of *E. coli* through the blood-brain barrier is a key step of the meningitis pathogenesis. Diabetes mellitus, alcoholism, cirrhosis, HIV infection and malignancies are some of the risk factors to develop *E coli* meningitis. A distant source is usually identified, either from the urinary or the digestive tract [19–22]. According to the World Health Organization, *Enterobacteriaceae*, including *Escherichia coli*, are among the critical priority antibiotic-resistant bacteria. Multidrug-resistant (MDR) *Escherichia coli* has been listed as a priority pathogen by the World Health Organization (WHO) due to emerging antimicrobial resistance

Staphylococcus, after group B Streptococcus (GBS)2 [16–18].

**1. Introduction**

**200**

(AMR) [23, 24].

## **2.** *Escherichia coli* **diseases and antibiotic resistance**

*E. coli* causes a wide range of diseases that can be assigned to either intestinal caused by intestinal *E. coli* (InPEC) or extraintestinal caused by extraintestinal *E. coli* (ExPEC) [25]. The most important diseases are as follows:

#### **2.1 ExPEC-associated cystitis and antibiotic resistance**

Cystitis is a common and expensive condition that impacts humans of different age groups from the neonate till geriatric age group. It is a pathogenic inflammation of the lower urinary tract. Women are more commonly afflicted with UTIs, and they are caused by common pathogens such as *Escherichia coli* (86%) [26]. Uropathogenic *Escherichia coli* (UPEC) is significantly associated with cystitis via sets of virulence factors (adhesins, siderophores, toxins, capsule production and protease) that assist its colonization, invasion, and survival within the host urinary system [27, 28]. High recurrence rates and increasing antimicrobial resistance among UPEC threaten to greatly increase the economic burden of these UTIs [5]. The resistance rate of Iraqi local UPEC to different antibiotic classes is summarized in **Table 1**. The resistance genes are listed in **Table 2**.

The average resistance rate is as follows: cefotaxime (77%), ceftriaxone (70%), ciprofloxacin (45.47%), amikacin (23.42%), gentamycin (45.69%) and imipenem (6.06%). Resistance to beta-lactams was attributed to many mechanisms, and one of them is to the modifying enzymes especially *blaTEM*, *blaSHV*, *blaCTX-M*, *blaOXA*, *blaPER* and *blaVIM*, while resistance to ciprofloxacin was interpreted



**203**

bacterial [58–60].

**Table 2.**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

Beta-lactam *blaCTX-M14, blaCTX-M15*

Beta-lactams *blaTEM, blaCTX-M, blaSHV blaOXA*

Aminoglycosides *aac(6)-Ib, aph(3)-I, aph(3)-IIa*

*Antibiotic resistance genes among Iraqi local UPEC.*

*aac(3)-IV*

*blaCTX-M24, blaCTX-M27*

*aph(3)-Ib, ant(3)-I, aac(3)-II*

Beta-lactams *blaTEM, blaPER, blaVIM and blaCTX-M-2, blaTEM,*

due to the presence of *qnrA*, *qnrB*, *qnrD* and *qnrS* genes [9, 29–37]. Resistance to aminoglycosides among UPEC may be mediated by *aac(6)-Ib*, *aph(3)-I*, *aph(3)-IIa*,

Beta-lactams *blaCTX-M* Karbala [37]

**Antibiotic class Genes Province Reference** Quinolones *qnrA, qnrB, qnrD, qnrS* Babylon [9] Beta-lactam *blaTEM, blaCTX-M* Sulemania [29] Beta-lactam *blaTEM, blaCTX-M, blaSHV* Najaf [30–32] Beta-lactam *blaSHV* Anbar [33] Beta-lactam *blaTEM, blaCTX-M, blaSHV, blaOXA, AmpC* Babylon [34]

Duhok [35]

Wasit [36]

Baghdad [38]

Najaf [31, 39]

Lower respiratory tract infections are a leading cause of morbidity and death worldwide. Optimizing the treatment of respiratory tract infections (RTIs) caused by multidrug-resistant (MDR) *Escherichia coli* has become challenging with existing antibiotic options. *E. coli* pathogens have various virulence factors that determine their pathogenesis and antimicrobial resistance (AMR) mechanisms [38]. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance [56, 57]. Physician visits for respiratory tract infections (RTI) commonly result in an antibiotic prescription, despite the fact that most upper RTIs are viral in nature. In these cases, antibiotics provide no benefit; thus, guidelines limit their recommended use to certain situations where the etiology is likely

Over- and inappropriate prescribing of antibiotics is highly prevalent in the primary care setting, especially for upper respiratory tract infections (URTIs). In the outpatient setting, URTIs account for approximately 50–70% of total antibiotic prescriptions, even though most cases are of viral origin [61, 62]. The overuse of broad-spectrum antibiotics, such as third-generation cephalosporins, amoxicillinclavulanate and fluoroquinolones, is strongly associated with the emergence of resistant strains, does not provide better clinical outcomes, and may lead to adverse events as well as unnecessary costs. Reducing unnecessary antibiotic prescriptions and the overuse of broad-spectrum agents may contain antimicrobial resistance and

The Iraqi studies dealing with antibiotic resistance among sepsis-associated *E. coli* are summarized in **Table 3**. Most *E. coli* strains isolated from bloodstream

*aph(3)-Ib*, *ant(3)-I*, *aac(3)-II* and *aac(3)-IV* [31, 39].

preserve the efficacy of existing antibiotics [63–65].

**2.2 ExPEC-associated sepsis and RTIs antibiotic resistance**

#### E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

## **Table 1.**


#### **Table 2.**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

Ciprofloxacin 258 41.73 Babylon [9, 34, 40, 41, 43, 52]

Levofloxacin 102 38.5 Babylon [42, 50]

Amikacin 322 25.1 Babylon [29, 34, 40, 41, 43, 51, 52]

Gentamycin 286 37.48 Babylon [29, 34, 40–43, 52]

Imipenem 42 11.9 Babylon [41]

 68.3 Baghdad [53] 72.5 Saladin [45] 25 Tikrit [54] 53.25 Duhok [49, 50] 24.8 Anbar [55] 52.6 Sulemania [51] 52.6 Erbil [39] 23.4 Missan [31] 40.6 Wasit [36]

14 0 Tikrit [54]

 24 Sulemania [44] 95 Karbala [45] 25.15 Saladin [46, 51] 5 Erbil [54] 5.9 Tikrit [48] 0.85 Kirkuk [48] 46 Duhok [49, 50] 9.8 Anbar [55] 11.1 Missan [31] 9.8 Wasit [36]

 74.35 Sulemania [30] 22.2 Najaf [45] 75 Saladin [46] 64.5 Erbil [54] 25 Tikrit [48] 51.2 Duhok [49, 50] 50 Anbar [55] 11.1 Missan [31] 46.1 Wasit [36]

 25 Anbar [33] 0 Wasit [36] 0 Zakho [47] 1.5 Kirkuk [48] 2.25 Duhok [49, 50] 4.5 Anbar [55] 4.7 Sulemania [51] 4.7 Erbil [54]

**Resistance % Province Reference**

**study**

**Antibiotic No. of isolate/**

**202**

**Table 1.**

*Distribution of antibiotic resistance among Iraqi local UPEC.*

*Antibiotic resistance genes among Iraqi local UPEC.*

due to the presence of *qnrA*, *qnrB*, *qnrD* and *qnrS* genes [9, 29–37]. Resistance to aminoglycosides among UPEC may be mediated by *aac(6)-Ib*, *aph(3)-I*, *aph(3)-IIa*, *aph(3)-Ib*, *ant(3)-I*, *aac(3)-II* and *aac(3)-IV* [31, 39].

#### **2.2 ExPEC-associated sepsis and RTIs antibiotic resistance**

Lower respiratory tract infections are a leading cause of morbidity and death worldwide. Optimizing the treatment of respiratory tract infections (RTIs) caused by multidrug-resistant (MDR) *Escherichia coli* has become challenging with existing antibiotic options. *E. coli* pathogens have various virulence factors that determine their pathogenesis and antimicrobial resistance (AMR) mechanisms [38]. The rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases. It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance [56, 57]. Physician visits for respiratory tract infections (RTI) commonly result in an antibiotic prescription, despite the fact that most upper RTIs are viral in nature. In these cases, antibiotics provide no benefit; thus, guidelines limit their recommended use to certain situations where the etiology is likely bacterial [58–60].

Over- and inappropriate prescribing of antibiotics is highly prevalent in the primary care setting, especially for upper respiratory tract infections (URTIs). In the outpatient setting, URTIs account for approximately 50–70% of total antibiotic prescriptions, even though most cases are of viral origin [61, 62]. The overuse of broad-spectrum antibiotics, such as third-generation cephalosporins, amoxicillinclavulanate and fluoroquinolones, is strongly associated with the emergence of resistant strains, does not provide better clinical outcomes, and may lead to adverse events as well as unnecessary costs. Reducing unnecessary antibiotic prescriptions and the overuse of broad-spectrum agents may contain antimicrobial resistance and preserve the efficacy of existing antibiotics [63–65].

The Iraqi studies dealing with antibiotic resistance among sepsis-associated *E. coli* are summarized in **Table 3**. Most *E. coli* strains isolated from bloodstream


#### E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

#### **Table 3.**

*Distribution of antibiotic resistance among Iraqi local sepsis-associated* E. coli*.*

were resistant to most antimicrobials particularly β-lactam antibiotics and third-generation cephalosporins. It might be that long-term exposure to these antimicrobials by patients infected with bacteremia leads to horizontal transfer of plasmid-resistant antimicrobial genes between different strains of bacteria [66].

The average resistance rate is as follows: cefotaxime (79%), ceftriaxone (76.7%), ciprofloxacin (23%), amikacin (21.95%), gentamycin (43.7%) and imipenem (3.5%). The third-generation cephalosporins were the most commonly prescribed antibiotics compiling 54.3% followed by quinolones 7.5% of all prescribed antibiotics. Cefotaxime and ceftriaxone seem to be the preferred prescribed antibiotic for both surgical and medical wards [32].

#### **2.3 InPEC-associated diarrheagenic infection and antibiotic resistance**

Diarrhea is one of the major causes of serious issues among children in the developing world. More than 4 million children die annually from diarrhea in developing world. Diarrheagenic *E. coli* (DEC) is the most common cause of bacterial diarrhea in children worldwide and responsible for about 600,000 deaths per year [73, 74]. Diarrheagenic *E. coli* infection manifests as watery or bloody diarrhea accompanied by mild-to-severe dehydration. Βeta-lactamases are a big problem when produced by DEC rendering the infection hard to be treated or untreatable. The arising of resistance toward extended-spectrum cephalosporins is most often due to hydrolyzing them by extended-spectrum β-lactamases (ESBLs) or due to AmpC. AmpC β-lactamases can prompt resistance to cephalothin, cefoxitin, cefazolin, most

**205**

**Table 4.**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

imipenem (8.18%).

penicillins and beta-lactamase inhibitor-beta-lactam combinations. *Escherichia coli* isolates with CTX-M ESBLs are spreading multiresistance in the community and in hospitals [75, 76]. The resistance rate of Iraqi local diarrheagenic *E. coli* to different antibiotic classes is summarized in **Table 4**. The resistance genes are listed in **Table 5**. The average resistance rate is as follows: cefotaxime (76.34%), ceftriaxone (79.87%), ciprofloxacin (26.3%), amikacin (31.21%), gentamycin (35.68%) and

The possible explanation to high level of resistance to this drug may be as a result of it being the most commonly available antibiotic used as a routine therapy among

**Antibiotic No. of isolate/study Resistance % Province Reference** Cefotaxime 18 92 Najaf [66]

Ceftriaxone 18 90 Najaf [66]

Ciprofloxacin 18 46 Najaf [66]

Amikacin 18, 535 44, 0.0 Najaf [66, 86]

Gentamycin 18, 535 46, 9.1 Najaf [66, 86]

Imipenem 18, 535 6, 0.0 Najaf [66, 86]

*Distribution of antibiotic resistance among Iraqi local diarrheagenic* E. coli*.*

89, 39, 114 82.9, 89.7, 100 Babylon [76–78] 100, 145 71.4, 96.4 Wasit [79, 80] 51, 37 4, 54 Baghdad [81, 82] 30 96.7 Tikrit [83]

89, 39, 114 74.6, 79.5, 100 Babylon [76–78] 81 Wasit [79] 40.5 Baghdad [82] 76.66 Basra [84] 96.7 Tikrit [83]

89, 39, 114 0.0, 15.8, 72.7 Babylon [76–78] 24, 51, 37 0.0, 8, 45.9 Baghdad [81, 82, 85] 145 25 Wasit [80] 30 23.3 Tikrit [83]

89, 39, 114 22.6, 12.8, 36.4 Babylon [76–78] 100, 145 7.1, 50 Wasit [79, 85] 24, 51, 37 16.6, 59, 67.5 Baghdad [81, 82, 85] 30 40 Tikrit [83]

89, 39, 114 2.8, 51.3, 54.5 Babylon [76–78] 24, 51, 37 0.0, 16, 100 Baghdad [81, 82, 85] 145 57.14 Wasit [80] 30 20 Tikrit [83]

89, 114 9.5, 36.4 Babylon [76–78] 100, 145 0.0, 0.0 Wasit [79, 80] 37 13.5 Baghdad [82] 163 0.0 Basra [84]

#### *Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

**Antibiotic No. of isolate/study Resistance % Province Reference** Cefotaxime 7 92 Najaf [66]

Ceftriaxone 7 90 Najaf [66]

Ciprofloxacin 7 46 Najaf [66]

Amikacin 7 44 Najaf [66]

Gentamycin 7 46 Najaf [66]

Imipenem 7 6 Najaf [66]

were resistant to most antimicrobials particularly β-lactam antibiotics and third-generation cephalosporins. It might be that long-term exposure to these antimicrobials by patients infected with bacteremia leads to horizontal transfer of plasmid-resistant antimicrobial genes between different strains of bacteria [66]. The average resistance rate is as follows: cefotaxime (79%), ceftriaxone (76.7%), ciprofloxacin (23%), amikacin (21.95%), gentamycin (43.7%) and imipenem (3.5%). The third-generation cephalosporins were the most commonly prescribed antibiotics compiling 54.3% followed by quinolones 7.5% of all prescribed antibiotics. Cefotaxime and ceftriaxone seem to be the preferred prescribed antibiotic for both surgical and

**2.3 InPEC-associated diarrheagenic infection and antibiotic resistance**

Diarrhea is one of the major causes of serious issues among children in the developing world. More than 4 million children die annually from diarrhea in developing world. Diarrheagenic *E. coli* (DEC) is the most common cause of bacterial diarrhea in children worldwide and responsible for about 600,000 deaths per year [73, 74]. Diarrheagenic *E. coli* infection manifests as watery or bloody diarrhea accompanied by mild-to-severe dehydration. Βeta-lactamases are a big problem when produced by DEC rendering the infection hard to be treated or untreatable. The arising of resistance toward extended-spectrum cephalosporins is most often due to hydrolyzing them by extended-spectrum β-lactamases (ESBLs) or due to AmpC. AmpC β-lactamases can prompt resistance to cephalothin, cefoxitin, cefazolin, most

*Distribution of antibiotic resistance among Iraqi local sepsis-associated* E. coli*.*

19, 42, 2 94.8, 95.2, 100 Duhok [67–69] 9 41 Karbala [70] 41 51.1 Baghdad [71]

19, 42 94.8, 93 Duhok [67, 68] 9 29 Karbala [70]

19 0.0 Duhok [67, 68]

19, 42, 2 0.0, 35.7, 0.0 Duhok [67–69] 9 30 Karbala [70] 41 22 Baghdad [71]

19, 42, 2 78.5, 52.4, 40 Duhok [67–69] 9 38 Karbala [70] 41, 17 22, 29.4 Baghdad [71, 72]

19, 42, 2 0.0, 9.5, 0.0 Duhok [67–69] 9 2 Karbala [70]

**204**

**Table 3.**

medical wards [32].

penicillins and beta-lactamase inhibitor-beta-lactam combinations. *Escherichia coli* isolates with CTX-M ESBLs are spreading multiresistance in the community and in hospitals [75, 76]. The resistance rate of Iraqi local diarrheagenic *E. coli* to different antibiotic classes is summarized in **Table 4**. The resistance genes are listed in **Table 5**.

The average resistance rate is as follows: cefotaxime (76.34%), ceftriaxone (79.87%), ciprofloxacin (26.3%), amikacin (31.21%), gentamycin (35.68%) and imipenem (8.18%).

The possible explanation to high level of resistance to this drug may be as a result of it being the most commonly available antibiotic used as a routine therapy among


#### **Table 4.**

*Distribution of antibiotic resistance among Iraqi local diarrheagenic* E. coli*.*


**Table 5.**

*Antibiotic resistance genes among Iraqi local diarrheagenic* E. coli*.*

gastrointestinal infections and people readily purchasing it across the counter for self-medication in last years. This could be a reflection of use and misuse of these antibiotics in the society. This finding is a result of the fact that outside the hospital environment the general population has easy access to various antibiotics from any pharmacy without prescription from a doctor [82].

#### **2.4 ExPEC-associated vaginosis and antibiotic resistance**

Bacterial vaginosis (BV) is the most common vaginal infections among women in reproductive age. It is a condition of vaginal flora imbalance, in which the typically plentiful H2O2-producing lactobacilli are scarce and other bacteria such as *E. coli* are abundant [87, 88]. Multi-drug resistant cervicovaginal *Escherichia coli* (CVEC) infections are a serious health problem. Bacteria use several strategies to avoid the effects of antimicrobial agents and have evolved a highly efficient means for clonal spread and for the dissemination of resistance traits [4]. Extendedspectrum β-lactamases (ESBLs) are capable of hydrolyzing broad-spectrum cephalosporins and monobactams. In addition, ESBL-producing organisms exhibit co-resistance to many other classes of antibiotics resulting in limitation of therapeutic options. Vaginal *E. coli* represents a real threat especially to neonates; however, little information is available regarding its antibiotic resistance [89, 90]. The resistance rate of Iraqi local cervicovaginal *E. coli* to different antibiotic classes is summarized in **Table 6**. The resistance genes are listed in **Table 7**.

The average resistance rate is as follows: cefotaxime (75%), ceftriaxone (47.5%), ciprofloxacin (29.4%), gentamycin (25.4%) and imipenem (7.8%).

#### **2.5 ExPEC-associated otitis media, meningitis and cholecystitis infection and antibiotic resistance**

Ear infection is a common clinical problem throughout the world and the major cause of preventable hearing loss in the developing world [92]. Its chronic form is a serious problem in all age groups with less chance of recovery. In certain cases,


**207**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

*Antibiotic resistance genes among Iraqi local cervicovaginal* E. coli*.*

this condition can lead to serious life-threatening complications, such as hearing impairment, brain abscesses or meningitis, mostly in childhood and late in life [93]. *E. coli* is one of the major causative agents of ear infection. The burden and prevalence of ear infection are more intense in developing countries due to the poor living standard and hygienic conditions along with a lack of proper nutrition. Increased antimicrobial resistance is one of the greatest global public health challenges, which has been accelerated by overprescription of antibiotics worldwide. Infection with antibiotic-resistant bacteria may cause severe illness, increased mortality rates and an increased risk of complications and admission to hospital and longer stay. *E. coli* was the most prevalent multi-antibiotic-resistant pathogenic bacteria isolated from

**Antibiotic class Genes Province Reference** Beta-lactamases *blaCTX-M*, *blaSHV*, *blaOXA* Wasit [91]

Gram-negative bacillary meningitis continues to be an important cause of mortality and morbidity (15% and 50%, respectively) throughout the world despite advances in antimicrobial chemotherapy and supportive care [97]. *E. coli* is the most common Gram-negative bacillary organism causing meningitis. Recent reports of *E. coli* strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. *E. coli* meningitis follows a high degree of bacteremia and invasion of the

Cholecystitis is most often caused by gall stones. Gall stones are one of the most common disorders of the gastrointestinal tract. Bacterial infection accounts for 50–85% of the disease's onset. *Escherichia coli* was the main biliary pathogenic microorganism [99]. It is strongly associated with retrograde bacterial infection and is an inflammatory disease that can be fatal if inappropriately treated [100]. The resistance rate of Iraqi local *E. coli* isolated from otitis media, meningitis and cholecystitis to different antibiotic classes is summarized in **Table 8**. The resistance

The average resistance rate is as follows: cefotaxime (72.57%), ceftriaxone (68.39%), ciprofloxacin (8.5%), gentamycin (42.46%) and imipenem (0%).

A wound can represent a simple or a severe disorder to an organ (such as the skin) or a tissue and can spread to other tissues and anatomical structures (e.g., subcutaneous tissue, muscles, tendons, nerves, vessels and even to the bone). Among all human body (HB) organs, the skin is without doubt the most exposed to impairment and injury, scratches and burns. By damaging the epithelium and connective structures, the HB's capability to provide protection from the outer environment is weakened [109]. An improper repair process can cause severe damage, like the loss of skin, initiation of an infection, with consequent harms to the subjacent tissues and even systemic ones. The most common and inevitable impediment to

Skin and soft tissue infections (SSTIs) are one of the most common infections in patients of all age groups. The most common causative agents are *Staphylococcus aureus* and aerobic streptococci. However, several reports associating the *Escherichia coli* with SSTI have been published: *E. coli* was found to be the causative agent of neonatal omphalitis, cellulitis localized to lower or upper limbs, necrotizing fasciitis,

**2.6 ExPEC-associated wound infection and antibiotic resistance**

wound healing is the installation of an infection [110].

suspected patient ear discharges with otitis media [94–96].

blood-brain barrier [21, 98].

**Table 7.**

genes are listed in **Table 9**.

**Table 6.**

*Distribution of antibiotic resistance among Iraqi local cervicovaginal* E. coli*.*

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*


**Table 7.**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

pharmacy without prescription from a doctor [82].

*Antibiotic resistance genes among Iraqi local diarrheagenic* E. coli*.*

**Table 5.**

**2.4 ExPEC-associated vaginosis and antibiotic resistance**

gastrointestinal infections and people readily purchasing it across the counter for self-medication in last years. This could be a reflection of use and misuse of these antibiotics in the society. This finding is a result of the fact that outside the hospital environment the general population has easy access to various antibiotics from any

**Antibiotic class Genes Province Reference** Beta-lactams *blaTEM*, *blaCTX-M*, *blaSHV*, *blaOXA*, *AmpC* Najaf [86]

Bacterial vaginosis (BV) is the most common vaginal infections among women

The average resistance rate is as follows: cefotaxime (75%), ceftriaxone (47.5%),

Ear infection is a common clinical problem throughout the world and the major cause of preventable hearing loss in the developing world [92]. Its chronic form is a serious problem in all age groups with less chance of recovery. In certain cases,

**Antibiotic No. of isolate/study Resistance % Province Reference** Cefotaxime 32 62.5 Babylon [88]

Ceftriaxone 32 50 Babylon [88]

Ciprofloxacin 51 29.4 Wasit [91] Gentamycin 51 25.4 Wasit [91] Imipenem 32 15.6 Babylon [88]

*Distribution of antibiotic resistance among Iraqi local cervicovaginal* E. coli*.*

51 86.2 Wasit [91]

51 45 Wasit [91]

51 0.0 Wasit [91]

**2.5 ExPEC-associated otitis media, meningitis and cholecystitis infection and** 

in reproductive age. It is a condition of vaginal flora imbalance, in which the typically plentiful H2O2-producing lactobacilli are scarce and other bacteria such as *E. coli* are abundant [87, 88]. Multi-drug resistant cervicovaginal *Escherichia coli* (CVEC) infections are a serious health problem. Bacteria use several strategies to avoid the effects of antimicrobial agents and have evolved a highly efficient means for clonal spread and for the dissemination of resistance traits [4]. Extendedspectrum β-lactamases (ESBLs) are capable of hydrolyzing broad-spectrum cephalosporins and monobactams. In addition, ESBL-producing organisms exhibit co-resistance to many other classes of antibiotics resulting in limitation of therapeutic options. Vaginal *E. coli* represents a real threat especially to neonates; however, little information is available regarding its antibiotic resistance [89, 90]. The resistance rate of Iraqi local cervicovaginal *E. coli* to different antibiotic classes

is summarized in **Table 6**. The resistance genes are listed in **Table 7**.

ciprofloxacin (29.4%), gentamycin (25.4%) and imipenem (7.8%).

**antibiotic resistance**

**206**

**Table 6.**

*Antibiotic resistance genes among Iraqi local cervicovaginal* E. coli*.*

this condition can lead to serious life-threatening complications, such as hearing impairment, brain abscesses or meningitis, mostly in childhood and late in life [93]. *E. coli* is one of the major causative agents of ear infection. The burden and prevalence of ear infection are more intense in developing countries due to the poor living standard and hygienic conditions along with a lack of proper nutrition. Increased antimicrobial resistance is one of the greatest global public health challenges, which has been accelerated by overprescription of antibiotics worldwide. Infection with antibiotic-resistant bacteria may cause severe illness, increased mortality rates and an increased risk of complications and admission to hospital and longer stay. *E. coli* was the most prevalent multi-antibiotic-resistant pathogenic bacteria isolated from suspected patient ear discharges with otitis media [94–96].

Gram-negative bacillary meningitis continues to be an important cause of mortality and morbidity (15% and 50%, respectively) throughout the world despite advances in antimicrobial chemotherapy and supportive care [97]. *E. coli* is the most common Gram-negative bacillary organism causing meningitis. Recent reports of *E. coli* strains producing CTX-M-type or TEM-type extended-spectrum β-lactamases create a challenge. *E. coli* meningitis follows a high degree of bacteremia and invasion of the blood-brain barrier [21, 98].

Cholecystitis is most often caused by gall stones. Gall stones are one of the most common disorders of the gastrointestinal tract. Bacterial infection accounts for 50–85% of the disease's onset. *Escherichia coli* was the main biliary pathogenic microorganism [99]. It is strongly associated with retrograde bacterial infection and is an inflammatory disease that can be fatal if inappropriately treated [100]. The resistance rate of Iraqi local *E. coli* isolated from otitis media, meningitis and cholecystitis to different antibiotic classes is summarized in **Table 8**. The resistance genes are listed in **Table 9**.

The average resistance rate is as follows: cefotaxime (72.57%), ceftriaxone (68.39%), ciprofloxacin (8.5%), gentamycin (42.46%) and imipenem (0%).

#### **2.6 ExPEC-associated wound infection and antibiotic resistance**

A wound can represent a simple or a severe disorder to an organ (such as the skin) or a tissue and can spread to other tissues and anatomical structures (e.g., subcutaneous tissue, muscles, tendons, nerves, vessels and even to the bone). Among all human body (HB) organs, the skin is without doubt the most exposed to impairment and injury, scratches and burns. By damaging the epithelium and connective structures, the HB's capability to provide protection from the outer environment is weakened [109]. An improper repair process can cause severe damage, like the loss of skin, initiation of an infection, with consequent harms to the subjacent tissues and even systemic ones. The most common and inevitable impediment to wound healing is the installation of an infection [110].

Skin and soft tissue infections (SSTIs) are one of the most common infections in patients of all age groups. The most common causative agents are *Staphylococcus aureus* and aerobic streptococci. However, several reports associating the *Escherichia coli* with SSTI have been published: *E. coli* was found to be the causative agent of neonatal omphalitis, cellulitis localized to lower or upper limbs, necrotizing fasciitis,


#### E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

#### **Table 8.**

*Distribution of antibiotic resistance among Iraqi local* E. coli *associated with otitis media, meningitis and cholecystitis.*


#### **Table 9.**

*Antibiotic resistance genes among Iraqi local* E. coli *associated with otitis media, meningitis and cholecystitis.*

surgical site infections, infections after burn injuries and others [111, 112]. Cellulitis due to *Escherichia coli* is rare and usually secondary to a cutaneous portal of entry. Skin and soft tissue infections (SSTIs) secondary to *E. coli* bacteremia have been reported exclusively in immunodeficient patients. The resistance rate of Iraqi local *E. coli* isolated from wound infection to different antibiotic classes is summarized in **Table 10**. The resistance genes are listed in **Table 11**.

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

**Antibiotic No. of isolate/study Resistance % Province Reference** Cefotaximes 7 85 Karbala [113]

Ceftriaxone 7 77 Karbala [113]

Ciprofloxacin 7 42 Karbala [113]

Levofloxacin 2 20 Anbar [114]

Amikacin 2 20 Anbar [114]

 100 Baghdad [101] 90 Anbar [114] 33.33 Karbala [115] 100 Baghdad [116] 88.09 Baghdad [117] 74.5 Najaf [118]

 90.57 Baghdad [101] 90 Anbar [114] 100 Baghdad [116] 100 Erbil [119] 83.8 Erbil [120] 75 Erbil [121] 68.6 Najaf [118]

 98.11 Baghdad [101] 20 Anbar [114] 100 Karbala [115] 50 Baghdad [116] 85.8 Erbil [119] 73.8 Baghdad [117] 54.4 Erbil [120] 16.66 Erbil [121] 35.2 Najaf [118] 85.7 Diyala [122]

 0.0 Baghdad [116] 85.8 Erbil [119] 73.8 Baghdad [117] 17.7 Erbil [121]

 22.22 Karbala [115] 75 Baghdad [116] 14.2 Erbil [119] 1.9 Erbil [120] 18.33 Erbil [121] 39.2 Najaf [118]


#### *Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

**Antibiotic No. of isolate/study Resistance % Province Reference** Cefotaxime 93 100 Anbar [101]

Ceftriaxone 93 90.57 Anbar [101]

Ciprofloxacin 10 20 Basra [105]

Levofloxacin 22 62 Najaf [102] Amikacin 10 20 Basra [105]

Gentamycin 10 20 Basra [105]

Imipenem 22 0 Najaf [102]

**Antibiotic class Genes Province Reference** Beta-lactamases *acrAB* Anbar [101] Quinolone *gyrA*, *parC* Anbar [101] Beta-lactamases *blaCTX-M*, *blaSHV*, *blaOXA*, *blaTEM* Najaf [102] Beta-lactamases *blaCTX-M*, *blaSHV*, *blaOXA*, *blaTEM* Al-Qadisiyah [108]

*Distribution of antibiotic resistance among Iraqi local* E. coli *associated with otitis media, meningitis and* 

 76 Najaf [102] 100 Baghdad [103] 14.29 Babylon [104]

 76 Najaf [102] 50 Baghdad [103] 57 Babylon [104]

 98.11 Anbar [101] 76 Najaf [102] 0.0 Tikrit [106] 14.29 Babylon [104]

 14 Najaf [102] 0.0 Baghdad [103] 0.0 Tikrit [106]

 100 Thi-Qar [107] 44.8 Najaf [102] 50 Baghdad [103] 0.0 Babylon [104]

surgical site infections, infections after burn injuries and others [111, 112]. Cellulitis due to *Escherichia coli* is rare and usually secondary to a cutaneous portal of entry. Skin and soft tissue infections (SSTIs) secondary to *E. coli* bacteremia have been reported exclusively in immunodeficient patients. The resistance rate of Iraqi local *E. coli* isolated from wound infection to different antibiotic classes is summarized in

*Antibiotic resistance genes among Iraqi local* E. coli *associated with otitis media, meningitis and cholecystitis.*

**Table 10**. The resistance genes are listed in **Table 11**.

**Table 8.**

**Table 9.**

*cholecystitis.*


#### E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

#### **Table 10.**

*Distribution of antibiotic resistance among Iraqi local* E. coli *associated with wound infections.*


#### **Table 11.**

*Antibiotic resistance genes among Iraqi local* E. coli *associated with wound infections.*

The average resistance rate is as follows: cefotaximes (81.56%), ceftriaxone (85.62%), ciprofloxacin (60.15%), levofloxacin (39.54%), amikacin (27.26%), gentamycin (56.97%) and imipenem (5.4%).

**211**

**Author details**

Hussein O.M. Al-Dahmoshi, Noor S.K. Al-Khafaji\* and Mohammed H.O. Al-Allak Biology Department, College of Science, University of Babylon, Hilla, Iraq

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: noorvaccine@gmail.com

provided the original work is properly cited.

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

**Antibiotic No. of isolate/study Resistance % Province Reference** Gentamycin 7 55 Karbala [113]

Imipenem 2 10 Anbar [114]

*Distribution of antibiotic resistance among Iraqi local* E. coli *associated with wound infections.*

*Antibiotic resistance genes among Iraqi local* E. coli *associated with wound infections.*

gentamycin (56.97%) and imipenem (5.4%).

**Antibiotic class Genes Province Reference** Beta-lactamases *blaNDM-1* Baghdad [123] Carbapenem *blaIMP* Baghdad [124] Beta-lactamases *blaNDM-1* Basra [125] Beta-lactamases *blaCTX-M* Erbil [121] Beta-lactamases *blaTEM*, *blaSHV*, *blaOXA51* Babylon [126]

The average resistance rate is as follows: cefotaximes (81.56%), ceftriaxone (85.62%), ciprofloxacin (60.15%), levofloxacin (39.54%), amikacin (27.26%),

 90 Anbar [114] 66.67 Karbala [115] 57.1 Erbil [119] 35.71 Baghdad [117] 40.6 Erbil [120] 25 Erbil [121] 78.4 Najaf [118] 64.3 Diyala [122]

 22.2 Karbala [115] 0.0 Baghdad [116] 0.0 Erbil [119] 4.76 Baghdad [117] 1.25 Erbil [120] 5 Erbil [121] 0.0 Najaf [118]

**210**

**Table 10.**

**Table 11.**

#### **Author details**

Hussein O.M. Al-Dahmoshi, Noor S.K. Al-Khafaji\* and Mohammed H.O. Al-Allak Biology Department, College of Science, University of Babylon, Hilla, Iraq

\*Address all correspondence to: noorvaccine@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Gomes TA, Elias WP, Scaletsky IC, Guth BE, Rodrigues JF, Piazza RM, et al. Diarrheagenic *Escherichia coli*. Brazilian Journal of Microbiology. 2016;**47**:3-30. DOI: 10.1016/j.bjm.2016.10.015

[2] Foxman B. The epidemiology of urinary tract infection. Nature Reviews Urology. 2010;**7**(12):653. DOI: 10.1038/ nrurol.2010.190

[3] Foxman B, Wu J, Farrer EC, Goldberg DE, Younger JG, Xi C. Early development of bacterial community diversity in emergently placed urinary catheters. BMC Research Notes. 2012;**5**(1):332. DOI: 10.1186/1756-0500-5-332

[4] Kaper JB, Nataro JP, Mobley HL. Pathogenic *Escherichia coli*. Nature Reviews Microbiology. 2004;**2**(2):123- 140. DOI: 10.1038/nrmicro818

[5] Cabrera-Sosa L, Ochoa TJ. *Escherichia coli* diarrhea. In: Hunter's Tropical Medicine and Emerging Infectious Diseases. 10th ed. Elsevier. 2020. pp. 481-485. DOI: 10.1016/ B978-0-323-55512-8.00046-6

[6] Zhang J, Xu Y, Ling X, Zhou Y, Lin Z, Huang Z, et al. Identification of diarrheagenic *Escherichia coli* by a new multiplex PCR assay and capillary electrophoresis. Molecular and Cellular Probes. 2020;**49**:101477. DOI: 10.1016/j. mcp.2019.101477

[7] Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: Epidemiology, mechanisms of infection and treatment options. Nature Reviews Microbiology. 2015;**13**(5): 269-284. DOI: 10.1038/nrmicro3432

[8] Toval F, Köhler CD, Vogel U, Wagenlehner F, Mellmann A, Fruth A, et al. Characterization of *Escherichia coli* isolates from hospital inpatients or outpatients with urinary tract infection. Journal of Clinical Microbiology. 2014;**52**(2):407-418. DOI: 10.1128/ JCM.02069-13

[9] Al-Hasnawy HH, Jodi MR, Hamza HJ. Molecular characterization and sequence analysis of plasmid-mediated quinolone resistance genes in extendedspectrum beta-lactamases producing uropathogenic *Escherichia coli* in Babylon Province, Iraq. Reviews in Medical Microbiology. 2018;**29**(3):129-135. DOI: 10.1097/MRM.0000000000000136

[10] Melsen WG, Rovers MM, Groenwold RH, Bergmans DC, Camus C, Bauer TT, et al. Attributable mortality of ventilator-associated pneumonia: A meta-analysis of individual patient data from randomised prevention studies. The Lancet Infectious Diseases. 2013;**13**(8):665-671. DOI: 10.1016/ S1473-3099(13)70081-1

[11] Chastre J, Fagon JY. Ventilatorassociated pneumonia. American Journal of Respiratory and Critical Care Medicine. 2002;**165**(7):867-903. DOI: 10.1164/ajrccm.165.7.2105078

[12] Russo TA, Johnson JR. Medical and economic impact of extraintestinal infections due to *Escherichia coli*: Focus on an increasingly important endemic problem. Microbes and Infection. 2003;**5**(5):449-456. DOI: 10.1016/ S1286-4579(03)00049-2

[13] Fihman V, Messika J, Hajage D, Tournier V, Gaudry S, Magdoud F, et al. Five-year trends for ventilatorassociated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption. International Journal of Antimicrobial Agents. 2015;**46**(5):518-525. DOI: 10.1016/j.ijantimicag.2015.07.010

[14] Kollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, et al. A randomized trial of the amikacin

**213**

019-00250-8

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

> report and literature review. World Neurosurgery. 2019;**126**:619-623. DOI:

[21] Kasimahanti R, Satish SK, Anand M. Community-acquired *Escherichia coli* meningitis with ventriculitis in an adult—A rare case report. Journal of Intensive Care. 2018;**6**(1):1-5. DOI:

10.1016/j.wneu.2019.02.243

10.1186/s40560-018-0332-6

[22] Bichon A, Aubry C, Dubourg G, Drouet H, Lagier JC, Raoult D, et al. *Escherichia coli* spontaneous community-

acquired meningitis in adults: A case report and literature review. International Journal of Infectious Diseases. 2018;**67**:70-74. DOI: 10.1016/j.

[23] Shrivastava SR, Shrivastava PS, Ramasamy J. World health organization releases global priority list of antibioticresistant bacteria to guide research, discovery, and development of new antibiotics. Journal of Medical Society. 2018;**32**:76-77. DOI: 10.4103/jms.

[24] Rodrigo-Troyano A, Sibila O. The respiratory threat posed by multidrug resistant gram-negative bacteria.

Respirology. 2017;**22**(7):1288-1299. DOI:

[25] Masters N, Wiegand A, Ahmed W, Katouli M. *Escherichia coli* virulence genes profile of surface waters as an indicator of water quality. Water Research. 2011;**45**(19):6321-6333. DOI:

[26] Markowitz MA, Wood LN, Raz S, Miller LG, Haake DA, Kim JH. Lack of uniformity among United States recommendations for diagnosis and management of acute, uncomplicated cystitis. International Urogynecology Journal. 2019;**30**(7):1187-1194. DOI:

[27] Zude I, Leimbach A, Dobrindt U. Prevalence of autotransporters in

10.1016/j.watres.2011.09.018

10.1007/s00192-018-3750-z

ijid.2017.12.003

jms\_25\_17

10.1111/resp.13115

fosfomycin inhalation system for the adjunctive therapy of Gram-negative ventilator-associated pneumonia: IASIS Trial. Chest. 2017;**151**(6):1239-1246. DOI: 10.1016/j.chest.2016.11.026

[15] Atia A, Elyounsi N, Abired A, Wanis A, Ashour A. Antibiotic resistance pattern of bacteria isolated from patients with upper respiratory tract infections; a four year study in Tripoli city. Preprint. 20182018080435. DOI: 10.20944/preprints201808.0435.v1

[16] Zhang K, Schneider D, Biswas R, Espriella MG, Rao J, Baffoe-Bonnie A. 2603. Biofilm formation as a predictive marker of prognosis for *Escherichia coli* sepsis. InOpen Forum Infectious Diseases. 2019;**6**:S904-S905. DOI: 10.1093/ofid/

[17] Gallardo L, Bauer M, Pannullo N, Michel LV. Determining the role of pal in *Escherichia coli* sepsis. The FASEB Journal. 2019;**33**(1\_supplement): 648-643. DOI: 10.1096/fasebj.2019.

[18] Pierpaoli E, Cirioni O, Simonetti O, Orlando F, Giacometti A, Lombardi P,

ofz360.2281

33.1\_supplement.648.3

et al. Potential application of berberine in the treatment of *Escherichia coli* sepsis. Natural Product Research. 2020;**31**:1-6. DOI: 10.1080/14786419.2020.1721729

[19] Xu X, Zhang L, Cai Y, Liu D, Shang Z, Ren Q, et al. Inhibitor discovery for the *E. coli* meningitis virulence factor IbeA from homology modeling and virtual screening. Journal of Computer-Aided Molecular Design. 2020;**34**(1):11-25. DOI: 10.1007/s10822-

[20] Kim M, Simon J, Mirza K, Swong K,

Johans S, Riedy L, et al. Spinal Intradural *Escherichia coli* abscess masquerading as a neoplasm in a pediatric patient with history of neonatal *E. coli* meningitis: A case *Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

fosfomycin inhalation system for the adjunctive therapy of Gram-negative ventilator-associated pneumonia: IASIS Trial. Chest. 2017;**151**(6):1239-1246. DOI: 10.1016/j.chest.2016.11.026

[15] Atia A, Elyounsi N, Abired A, Wanis A, Ashour A. Antibiotic resistance pattern of bacteria isolated from patients with upper respiratory tract infections; a four year study in Tripoli city. Preprint. 20182018080435. DOI: 10.20944/preprints201808.0435.v1

[16] Zhang K, Schneider D, Biswas R, Espriella MG, Rao J, Baffoe-Bonnie A. 2603. Biofilm formation as a predictive marker of prognosis for *Escherichia coli* sepsis. InOpen Forum Infectious Diseases. 2019;**6**:S904-S905. DOI: 10.1093/ofid/ ofz360.2281

[17] Gallardo L, Bauer M, Pannullo N, Michel LV. Determining the role of pal in *Escherichia coli* sepsis. The FASEB Journal. 2019;**33**(1\_supplement): 648-643. DOI: 10.1096/fasebj.2019. 33.1\_supplement.648.3

[18] Pierpaoli E, Cirioni O, Simonetti O, Orlando F, Giacometti A, Lombardi P, et al. Potential application of berberine in the treatment of *Escherichia coli* sepsis. Natural Product Research. 2020;**31**:1-6. DOI: 10.1080/14786419.2020.1721729

[19] Xu X, Zhang L, Cai Y, Liu D, Shang Z, Ren Q, et al. Inhibitor discovery for the *E. coli* meningitis virulence factor IbeA from homology modeling and virtual screening. Journal of Computer-Aided Molecular Design. 2020;**34**(1):11-25. DOI: 10.1007/s10822- 019-00250-8

[20] Kim M, Simon J, Mirza K, Swong K, Johans S, Riedy L, et al. Spinal Intradural *Escherichia coli* abscess masquerading as a neoplasm in a pediatric patient with history of neonatal *E. coli* meningitis: A case

report and literature review. World Neurosurgery. 2019;**126**:619-623. DOI: 10.1016/j.wneu.2019.02.243

[21] Kasimahanti R, Satish SK, Anand M. Community-acquired *Escherichia coli* meningitis with ventriculitis in an adult—A rare case report. Journal of Intensive Care. 2018;**6**(1):1-5. DOI: 10.1186/s40560-018-0332-6

[22] Bichon A, Aubry C, Dubourg G, Drouet H, Lagier JC, Raoult D, et al. *Escherichia coli* spontaneous communityacquired meningitis in adults: A case report and literature review. International Journal of Infectious Diseases. 2018;**67**:70-74. DOI: 10.1016/j. ijid.2017.12.003

[23] Shrivastava SR, Shrivastava PS, Ramasamy J. World health organization releases global priority list of antibioticresistant bacteria to guide research, discovery, and development of new antibiotics. Journal of Medical Society. 2018;**32**:76-77. DOI: 10.4103/jms. jms\_25\_17

[24] Rodrigo-Troyano A, Sibila O. The respiratory threat posed by multidrug resistant gram-negative bacteria. Respirology. 2017;**22**(7):1288-1299. DOI: 10.1111/resp.13115

[25] Masters N, Wiegand A, Ahmed W, Katouli M. *Escherichia coli* virulence genes profile of surface waters as an indicator of water quality. Water Research. 2011;**45**(19):6321-6333. DOI: 10.1016/j.watres.2011.09.018

[26] Markowitz MA, Wood LN, Raz S, Miller LG, Haake DA, Kim JH. Lack of uniformity among United States recommendations for diagnosis and management of acute, uncomplicated cystitis. International Urogynecology Journal. 2019;**30**(7):1187-1194. DOI: 10.1007/s00192-018-3750-z

[27] Zude I, Leimbach A, Dobrindt U. Prevalence of autotransporters in

**212**

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

Journal of Clinical Microbiology. 2014;**52**(2):407-418. DOI: 10.1128/

analysis of plasmid-mediated

[10] Melsen WG, Rovers MM,

S1473-3099(13)70081-1

[11] Chastre J, Fagon JY. Ventilatorassociated pneumonia. American Journal of Respiratory and Critical Care Medicine. 2002;**165**(7):867-903. DOI:

[12] Russo TA, Johnson JR. Medical and economic impact of extraintestinal infections due to *Escherichia coli*: Focus on an increasingly important endemic problem. Microbes and Infection. 2003;**5**(5):449-456. DOI: 10.1016/

10.1164/ajrccm.165.7.2105078

S1286-4579(03)00049-2

[13] Fihman V, Messika J, Hajage D, Tournier V, Gaudry S, Magdoud F, et al. Five-year trends for ventilatorassociated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption. International Journal of Antimicrobial Agents. 2015;**46**(5):518-525. DOI: 10.1016/j.ijantimicag.2015.07.010

[14] Kollef MH, Ricard JD, Roux D, Francois B, Ischaki E, Rozgonyi Z, et al. A randomized trial of the amikacin

[9] Al-Hasnawy HH, Jodi MR, Hamza HJ. Molecular characterization and sequence

quinolone resistance genes in extendedspectrum beta-lactamases producing uropathogenic *Escherichia coli* in Babylon Province, Iraq. Reviews in Medical Microbiology. 2018;**29**(3):129-135. DOI: 10.1097/MRM.0000000000000136

Groenwold RH, Bergmans DC, Camus C, Bauer TT, et al. Attributable mortality of ventilator-associated pneumonia: A meta-analysis of individual patient data from randomised prevention studies. The Lancet Infectious Diseases. 2013;**13**(8):665-671. DOI: 10.1016/

JCM.02069-13

**References**

nrurol.2010.190

[1] Gomes TA, Elias WP, Scaletsky IC, Guth BE, Rodrigues JF, Piazza RM, et al. Diarrheagenic *Escherichia coli*. Brazilian Journal of Microbiology. 2016;**47**:3-30.

DOI: 10.1016/j.bjm.2016.10.015

[3] Foxman B, Wu J, Farrer EC, Goldberg DE, Younger JG, Xi C. Early development of bacterial community diversity in emergently placed urinary catheters. BMC Research Notes. 2012;**5**(1):332. DOI: 10.1186/1756-0500-5-332

[4] Kaper JB, Nataro JP, Mobley HL. Pathogenic *Escherichia coli*. Nature Reviews Microbiology. 2004;**2**(2):123-

140. DOI: 10.1038/nrmicro818

[5] Cabrera-Sosa L, Ochoa TJ. *Escherichia coli* diarrhea. In: Hunter's Tropical Medicine and Emerging Infectious Diseases. 10th ed. Elsevier. 2020. pp. 481-485. DOI: 10.1016/ B978-0-323-55512-8.00046-6

[6] Zhang J, Xu Y, Ling X, Zhou Y, Lin Z, Huang Z, et al. Identification of diarrheagenic *Escherichia coli* by a new multiplex PCR assay and capillary electrophoresis. Molecular and Cellular Probes. 2020;**49**:101477. DOI: 10.1016/j.

[7] Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: Epidemiology, mechanisms of infection and treatment options. Nature Reviews Microbiology. 2015;**13**(5): 269-284. DOI: 10.1038/nrmicro3432

[8] Toval F, Köhler CD, Vogel U, Wagenlehner F, Mellmann A, Fruth A, et al. Characterization of *Escherichia coli* isolates from hospital inpatients or outpatients with urinary tract infection.

mcp.2019.101477

[2] Foxman B. The epidemiology of urinary tract infection. Nature Reviews Urology. 2010;**7**(12):653. DOI: 10.1038/

Escherichia coli: What is the impact of phylogeny and pathotype? International Journal of Medical Microbiology. 2014;**304**(3-4):243-256. DOI: 10.1016/j. ijmm.2013.10.006

[28] Behzadi P, Najafi A, Behzadi E, Ranjbar R. Microarray long oligo probe designing for *Escherichia coli*: An in-silico DNA marker extraction. Central European Journal of Urology. 2016;**69**(1):105. DOI: 10.1016/j.ijmm. 2013.10.006

[29] Saeed NM. Detection of extended spectrum beta-lactamase gene production by *E. coli* isolated from human and broiler in Sulemania province/Iraq. Journal of Zankoy Sulaimani-Part A. 2014;**16**:2. DOI: 10.17656/jzs.10296

[30] Alkhudhairy MK, Alshammari MM. Extended spectrum β-lactamaseproducing *Escherichia coli* isolated from pregnant women with asymptomatic UTI in Iraq. EurAsian Journal of BioSciences. 2019;**13**(2):1881-1889

[31] Alquraishi ZH, Alabbasy AJ, Alsadawi AA. Genotype and phenotype detection of *E. coli* isolated from children suffering from urinary tract infection. Journal of Global Pharmacy Technology. 2018;**10**(1):38-45

[32] Majeed HT, Aljanaby AA. Antibiotic susceptibility patterns and prevalence of some extended spectrum beta-lactamases genes in gram-negative bacteria isolated from patients infected with urinary tract infections in Al-Najaf City, Iraq. Avicenna Journal of Medical Biotechnology. 2019;**11**(2):192

[33] Al-Ouqaili MT. Molecular detection and sequencing of SHV gene encoding for extendedspectrum β-lactamases produced by multidrug resistance some of the gram-negative bacteria. International Journal of Green Pharmacy (IJGP). 2019;**12**(04):S910-S918. DOI: 10.22377/ ijgp.v12i04.2274

[34] Al-Charrakh AH, AL-Tememy AZ. Phenotypic and genotypic characterization of IRS-producing *Escherichia coli* isolated from patients with UTI in Iraq. Medical Journal of Babylon. 2015;**12**(1):80-95

[35] Michael NS, Saadi AT. Detection of bla CTX-M, bla TEM-01 and bla SHV genes in multidrug resistant uropathogenic *E. coli* isolated from patients with recurrent urinary tract infections. International Journal of Medical Research & Health Sciences. 2018;**7**(9):81-89

[36] Al-Mayahie S, Al Kuriashy JJ. Distribution of ESBLs among *Escherichia coli* isolates from outpatients with recurrent UTIs and their antimicrobial resistance. The Journal of Infection in Developing Countries. 2016;**10**(06): 575-583. DOI: 10.3855/jidc 6661

[37] Zirjawi AM, Hussein NH, Taha BM, Hussein JD. Molecular detection of Ctx-M-Β-lactamases in *Pseudomonas aerogenosa* strains isolated from corneal infections. European Journal of Biomedical. 2017;**4**(4):70-74

[38] Promite S, Saha SK. Escherichia coli in respiratory tract infections: Evaluating antimicrobial resistance and prevalence of fimA, neuC and iutA virulence genes. Gene Reports. 2020;**18**:100576. DOI: 10.1016/j. genrep.2019.100576

[39] Alm'amoori KO, Hadi ZJ, Almohana AM. Molecular investigation of aminoglycoside modifying enzyme among aminoglycoside-resistant uropathogenic *Escherichia coli* isolates from Najaf Hospitals, Iraq. Indian Journal of Public Health Research & Development. 2019;**10**(10):2298-2303. DOI: 10.5958/0976-5506.2019.03199.1

[40] Alhamdany MH. Antibiotic susceptibility of bacteria isolated from patients with diabetes mellitus and

**215**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

Medical Sciences. 2015;**19**(1):915-922.

susceptibility patterns of uropathogenic

Iraq. International Journal of Research

[48] Alsamarai AG, Ali S. Urinary Tract Infection in Female in Kirkuk City, Iraq: Causative Agents and Antibiogram. Vol. 5. WJPPS; 2016. pp. 261-273. DOI:

DOI: 10.15218/zjms.2015.0012

[47] Polse R, Yousif S, Assafi M. Prevalence and antimicrobial

*E. coli* among people in Zakho,

in Medical Sciences. 2016;**4**(4): 1219-1223. DOI: 10.18203/2320-6012.

10.20959/wjpps20166-6807

[49] Assafi MS, Ibrahim NM, Hussein NR, Taha AA, Balatay AA. Urinary bacterial profile and antibiotic susceptibility pattern among patients with urinary tract infection in Duhok city, Kurdistan region, Iraq. International Journal of Pure and Applied Sciences and Technology.

[50] Hussein NR, Daniel S, Salim K, Assafi MS. Urinary tract infections and antibiotic sensitivity patterns among women referred to Azadi Teaching Hospital, Duhok, Iraq. Avicenna Journal of Clinical Microbiology and Infection.

2017;**5**(2):27-30. DOI: 10.34172/

[51] Merza NS, Jubrael JM. The

Engineering. 2015;**1**(4):338-343

10.9734/BBJ/2013/3573

[52] Hindi NK, Hasson SO, Hindi SK. Bacteriological study of urinary tract infections with antibiotics susceptibility to bacterial isolates among honeymoon women in Al Qassim Hospital, Babylon Province, Iraq. Biotechnology Journal International. 2013;**3**:332-340. DOI:

prevalence of virulence factors among uropathogenic *Escherichia coli* strains isolated from different hospitals in Kurdistan Region-Iraq. International Journal of Bioinformatics and Biomedical

ijrms20160813

2015;**30**(2):54

ajcmi.2018.05

recurrent urinary tract infections in Babylon Province, Iraq. Medical Journal of Babylon. 2018;**15**(1):63-68. DOI:

10.4103/MJBL.MJBL\_16\_18

bsj.2019.16.4(Suppl.).0000

[42] AL-Sa'ady AT, Al-Mawla YH. Comparison of effects antibiotics and natural honey and extracts of plants on *Escherichia coli* growth isolated from different pathogenic cases. Journal of University of Babylon for Pure and Applied Sciences. 2019;**27**(3):420-434

[43] Abed ZH, Jarallah EM. Antibiotics susceptibility pattern of clinical and environmental *Escherichia coli* isolates from Babylon hospitals. In Journal of Physics: Conference Series. 2019;**1294**(6):062105. DOI: 0.1088/1742-6596/1294/6/062105

[44] Mohammed S, Ahmed M, Karem K. Incidence of multi-drug resistant *Escherichia coli* isolates from blood and urine in Kerbala, Iraq. Journal of Kerbala University.

[45] AL-Samarraie MQ, Omar MK, Yaseen AH, Mahmood MI. The wide spread of the gene haeomolysin (Hly) and the adhesion factor (Sfa) in the *E. coli* isolated from UTI. Journal of Pharmaceutical Sciences and Research.

[46] Mansoor IY, AL-Otraqchi KI, Saeed CH. Prevalence of urinary tract infections and antibiotics susceptibility pattern among infants and young children in Erbil city. Zanco Journal of

2014;**12**(4):222-227

2019;**11**(4):1298-1303

[41] Al-Hasnawy HH, Judi MR, Hamza HJ. The dissemination of multidrug resistance (MDR) and extensively drug resistant (XDR) among uropathogenic *E. coli* (UPEC) isolates from urinary tract infection patients in Babylon Province, Iraq. Baghdad Science Journal. 2019;**16** (4 Supplement):986-922. DOI: 10.21123/ *Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

recurrent urinary tract infections in Babylon Province, Iraq. Medical Journal of Babylon. 2018;**15**(1):63-68. DOI: 10.4103/MJBL.MJBL\_16\_18

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

[34] Al-Charrakh AH, AL-Tememy AZ.

characterization of IRS-producing *Escherichia coli* isolated from patients with UTI in Iraq. Medical Journal of

[35] Michael NS, Saadi AT. Detection of bla CTX-M, bla TEM-01 and bla SHV genes in multidrug resistant uropathogenic *E. coli* isolated from patients with recurrent urinary tract infections. International Journal of Medical Research & Health Sciences.

[36] Al-Mayahie S, Al Kuriashy JJ.

Distribution of ESBLs among *Escherichia coli* isolates from outpatients with recurrent UTIs and their antimicrobial resistance. The Journal of Infection in Developing Countries. 2016;**10**(06): 575-583. DOI: 10.3855/jidc 6661

[37] Zirjawi AM, Hussein NH, Taha BM, Hussein JD. Molecular detection of Ctx-M-Β-lactamases in *Pseudomonas aerogenosa* strains isolated from corneal

infections. European Journal of Biomedical. 2017;**4**(4):70-74

genrep.2019.100576

[39] Alm'amoori KO, Hadi ZJ,

[40] Alhamdany MH. Antibiotic susceptibility of bacteria isolated from patients with diabetes mellitus and

Almohana AM. Molecular investigation of aminoglycoside modifying enzyme among aminoglycoside-resistant uropathogenic *Escherichia coli* isolates from Najaf Hospitals, Iraq. Indian Journal of Public Health Research & Development. 2019;**10**(10):2298-2303. DOI: 10.5958/0976-5506.2019.03199.1

[38] Promite S, Saha SK. Escherichia coli in respiratory tract infections: Evaluating antimicrobial resistance and prevalence of fimA, neuC and iutA virulence genes. Gene Reports. 2020;**18**:100576. DOI: 10.1016/j.

Phenotypic and genotypic

Babylon. 2015;**12**(1):80-95

2018;**7**(9):81-89

Escherichia coli: What is the impact of phylogeny and pathotype? International Journal of Medical Microbiology. 2014;**304**(3-4):243-256. DOI: 10.1016/j.

[28] Behzadi P, Najafi A, Behzadi E, Ranjbar R. Microarray long oligo probe designing for *Escherichia coli*: An in-silico DNA marker extraction. Central European Journal of Urology. 2016;**69**(1):105. DOI: 10.1016/j.ijmm.

[29] Saeed NM. Detection of extended spectrum beta-lactamase gene production by *E. coli* isolated from human and broiler in Sulemania province/Iraq. Journal of Zankoy Sulaimani-Part A. 2014;**16**:2.

[30] Alkhudhairy MK, Alshammari MM.

Extended spectrum β-lactamaseproducing *Escherichia coli* isolated from pregnant women with asymptomatic UTI in Iraq. EurAsian Journal of BioSciences. 2019;**13**(2):1881-1889

[31] Alquraishi ZH, Alabbasy AJ,

Technology. 2018;**10**(1):38-45

[32] Majeed HT, Aljanaby AA.

bacteria isolated from patients infected with urinary tract infections in Al-Najaf City, Iraq. Avicenna Journal of Medical Biotechnology.

[33] Al-Ouqaili MT. Molecular detection and sequencing of SHV gene encoding for extendedspectrum β-lactamases produced by multidrug resistance some of the gram-negative bacteria. International Journal of Green Pharmacy (IJGP). 2019;**12**(04):S910-S918. DOI: 10.22377/

2019;**11**(2):192

ijgp.v12i04.2274

Antibiotic susceptibility patterns and prevalence of some extended spectrum beta-lactamases genes in gram-negative

Alsadawi AA. Genotype and phenotype detection of *E. coli* isolated from children suffering from urinary tract infection. Journal of Global Pharmacy

ijmm.2013.10.006

2013.10.006

DOI: 10.17656/jzs.10296

**214**

[41] Al-Hasnawy HH, Judi MR, Hamza HJ. The dissemination of multidrug resistance (MDR) and extensively drug resistant (XDR) among uropathogenic *E. coli* (UPEC) isolates from urinary tract infection patients in Babylon Province, Iraq. Baghdad Science Journal. 2019;**16** (4 Supplement):986-922. DOI: 10.21123/ bsj.2019.16.4(Suppl.).0000

[42] AL-Sa'ady AT, Al-Mawla YH. Comparison of effects antibiotics and natural honey and extracts of plants on *Escherichia coli* growth isolated from different pathogenic cases. Journal of University of Babylon for Pure and Applied Sciences. 2019;**27**(3):420-434

[43] Abed ZH, Jarallah EM. Antibiotics susceptibility pattern of clinical and environmental *Escherichia coli* isolates from Babylon hospitals. In Journal of Physics: Conference Series. 2019;**1294**(6):062105. DOI: 0.1088/1742-6596/1294/6/062105

[44] Mohammed S, Ahmed M, Karem K. Incidence of multi-drug resistant *Escherichia coli* isolates from blood and urine in Kerbala, Iraq. Journal of Kerbala University. 2014;**12**(4):222-227

[45] AL-Samarraie MQ, Omar MK, Yaseen AH, Mahmood MI. The wide spread of the gene haeomolysin (Hly) and the adhesion factor (Sfa) in the *E. coli* isolated from UTI. Journal of Pharmaceutical Sciences and Research. 2019;**11**(4):1298-1303

[46] Mansoor IY, AL-Otraqchi KI, Saeed CH. Prevalence of urinary tract infections and antibiotics susceptibility pattern among infants and young children in Erbil city. Zanco Journal of

Medical Sciences. 2015;**19**(1):915-922. DOI: 10.15218/zjms.2015.0012

[47] Polse R, Yousif S, Assafi M. Prevalence and antimicrobial susceptibility patterns of uropathogenic *E. coli* among people in Zakho, Iraq. International Journal of Research in Medical Sciences. 2016;**4**(4): 1219-1223. DOI: 10.18203/2320-6012. ijrms20160813

[48] Alsamarai AG, Ali S. Urinary Tract Infection in Female in Kirkuk City, Iraq: Causative Agents and Antibiogram. Vol. 5. WJPPS; 2016. pp. 261-273. DOI: 10.20959/wjpps20166-6807

[49] Assafi MS, Ibrahim NM, Hussein NR, Taha AA, Balatay AA. Urinary bacterial profile and antibiotic susceptibility pattern among patients with urinary tract infection in Duhok city, Kurdistan region, Iraq. International Journal of Pure and Applied Sciences and Technology. 2015;**30**(2):54

[50] Hussein NR, Daniel S, Salim K, Assafi MS. Urinary tract infections and antibiotic sensitivity patterns among women referred to Azadi Teaching Hospital, Duhok, Iraq. Avicenna Journal of Clinical Microbiology and Infection. 2017;**5**(2):27-30. DOI: 10.34172/ ajcmi.2018.05

[51] Merza NS, Jubrael JM. The prevalence of virulence factors among uropathogenic *Escherichia coli* strains isolated from different hospitals in Kurdistan Region-Iraq. International Journal of Bioinformatics and Biomedical Engineering. 2015;**1**(4):338-343

[52] Hindi NK, Hasson SO, Hindi SK. Bacteriological study of urinary tract infections with antibiotics susceptibility to bacterial isolates among honeymoon women in Al Qassim Hospital, Babylon Province, Iraq. Biotechnology Journal International. 2013;**3**:332-340. DOI: 10.9734/BBJ/2013/3573

[53] Ibrahim AA. Identification of iha and kpsMT virulence genes in *Escherichia coli* isolates with urinary tract infection in Iraqi patients. Indian Journal of Natural Sciences. 2019;**52**(9):16675-16682

[54] Al-Jebouri MM, Mdish SA. Antibiotic resistance pattern of bacteria isolated from patients of urinary tract infections in Iraq. Open Journal of Urology. 2013;**3**(2):124-131. DOI: 10.4236/oju.2013.32024

[55] Lafi SA, Alkarboly AA, Lafi MS. Bacterial urinary tract infection in adults, hit district Anbar governorate, west of Iraq. Egyptian Academic Journal of Biological Sciences, G. Microbiology. 2012;**4**(1):21-26, 10.21608/EAJBSG. 2012.16656

[56] Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, et al. Infectious Diseases Society of America. The epidemic of antibiotic-resistant infections: A call to action for the medical community from the Infectious Diseases Society of America. Clinical Infectious Diseases. 2008;**46**(2):155-164. DOI: 10.1086/524891

[57] Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infectious Diseases. 2014;**14**(1):13. DOI: 10.1186/1471-2334-14-13

[58] Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;**128**(6): 1053-1061. DOI: 10.1542/peds. 2011-1337

[59] Lee GC, Reveles KR, Attridge RT, Lawson KA, Mansi IA, Lewis JS, et al. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Medicine. 2014;**12**(1):96. DOI: 10.1186/1741-7015-12-96

[60] Hersh AL, Jackson MA, Hicks LA. Committee on infectious diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics. 2013;**132**(6):1146-1154. DOI: 10.1542/ peds.2013-3260

[61] Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010- 2011. Journal of the American Medical Association. 2016;**315**(17):1864-1873. DOI: 10.1001/jama.2016.4151

[62] Smieszek T, Pouwels KB, Dolk FC, Smith DR, Hopkins S, Sharland M, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. Journal of Antimicrobial Chemotherapy. 2018;**73**(suppl\_2): ii36-ii43. DOI: 10.1093/jac/dkx500

[63] Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, et al. Association of broad-vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. Journal of the American Medical Association. 2017;**318**(23):2325-2336. DOI: 10.1001/ jama.2017.18715

[64] Kreitmeyr K, von Both U, Pecar A, Borde JP, Mikolajczyk R, Huebner J. Pediatric antibiotic stewardship: Successful interventions to reduce broad-spectrum antibiotic use on general pediatric wards. Infection. 2017;**45**(4):493-504. DOI: 10.1007/ s15010-017-1009-0

[65] Poole NM, Shapiro DJ, Fleming-Dutra KE, Hicks LA, Hersh AL, Kronman MP. Antibiotic prescribing for children in United States emergency departments: 2009- 2014. Pediatrics. 2019;**143**(2): e20181056. DOI: 10.1542/peds. 2018-1056

**217**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

> analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;**380**(9859):2095-2128. DOI: 10.1016/S0140-6736(12)61728-0

Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study. The Lancet. 2013;**382**(9888):209-222. DOI: 10.1016/S0140-6736(13)60844-2

[75] Livermore DM, Woodford N. The β-lactamase threat in Enterobacteriaceae. Pseudomonas and Acinetobacter. Trends in Microbiology. 2006;**14**(9):413-420. DOI: 10.1016/j.

[76] Al-Marzoqi AH, Aziz HW,

Dulaimi TH. Genotype, phenotype and virulence genes markers in *Escherichia coli*: Molecular characterization and antimicrobial susceptibility associated with Diarrhoea among children in Babil province, Iraq. International Journal of Biochemistry, Bioinformatics a nd Biotechnology Studies. 2019;**4**(1):11-20

[77] Al-Dahmoshi HO, Al-Yassari AK,

[78] Al-Saadi ZH, Tarish AH, Saeed EA. Phenotypic detection and antibiotics resistance pattern of local serotype of *E. coli* O157: H7 from children with acute diarrhea in Hilla city/Iraq. Journal of Pharmaceutical Sciences and Research.

[79] Abdul-hussein ZK, Raheema RH, Inssaf AI. Molecular diagnosis of diarrheagenic *E. coli* infections among

Al-Saad NF, Al-Dabagh NN, Al-Khafaji NS, Mahdi RK, et al. Occurrence of AmpC, MBL, CRE and ESBLs among diarrheagenic *Escherichia coli* recovered from Infantile Diarrhea, Iraq. Journal of Pharmaceutical and Biomedical Sciences. 2015;**5**:189-195

2018;**10**(3):604-609

tim.2006.07.008

[74] Kotloff KL, Nataro JP,

[66] Aljanaby AA, Alfaham QM. Phenotypic and molecular

ajbmb.2017.65.78

2019;**13**(2):84-95

2016;**11**:131-139

characterization of some virulence factors in multidrug resistance *Escherichia coli* isolated from different clinical infections in Iraq. American Journal of Biochemistry and Molecular Biology. 2017;**7**:65-78. DOI: 10.3923/

[67] Al-Delaimi MS, Nabeel M. Early onset neonatal sepsis: Bacteriological antimicrobial susceptibility study in Duhok Province, Iraq. Journal of University of Babylon for Pure and Applied Sciences. 2019;**27**(3):196-212

[68] ABDULRAHMAN IS, SAADI AT. Bacterial isolates and their antimicrobial resistance patterns in neonatal sepsis recorded at Hevi Teaching Hospital in Duhok City/Kurdistan Region of Iraq. Duhok Medical Journal.

[69] Saadi AT, Garjees NA, Rasool AH. Antibiogram profile of septic meningitis among children in Duhok, Iraq. Saudi Medical Journal. 2017;**38**(5):517

[70] Al-mousawi MR. Bacterial profile and antibiogram of bacteremic children in Karbala city, Iraq. Karbala Journal of Pharmaceutical Sciences.

[71] Raham TF, Abood AM. Bacterial profile and antimicrobial susceptibility in neonatal sepses, Al-Alwyia Pediatric Teaching Hospital in Baghdad. Al-Kindy College Medical Journal. 2017;**13**(2):21-25

Microbiological profile of neonatal septicemia. Iraqi Postgraduate Medical

[73] Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic

[72] Ibrahim SA, Rahma S.

Journal. 2012;**11**:13-18

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

[60] Hersh AL, Jackson MA, Hicks LA. Committee on infectious diseases. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics. 2013;**132**(6):1146-1154. DOI: 10.1542/

[61] Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, et al. Prevalence of

DOI: 10.1001/jama.2016.4151

inappropriate antibiotic prescriptions among US ambulatory care visits, 2010- 2011. Journal of the American Medical Association. 2016;**315**(17):1864-1873.

[62] Smieszek T, Pouwels KB, Dolk FC, Smith DR, Hopkins S, Sharland M, et al. Potential for reducing inappropriate antibiotic prescribing in English primary care. Journal of Antimicrobial Chemotherapy. 2018;**73**(suppl\_2): ii36-ii43. DOI: 10.1093/jac/dkx500

[63] Gerber JS, Ross RK, Bryan M,

Wasserman R, et al. Association of broad-vs narrow-spectrum antibiotics with treatment failure, adverse events, and quality of life in children with acute respiratory tract infections. Journal of the American Medical Association. 2017;**318**(23):2325-2336. DOI: 10.1001/

[64] Kreitmeyr K, von Both U, Pecar A, Borde JP, Mikolajczyk R, Huebner J. Pediatric antibiotic stewardship: Successful interventions to reduce broad-spectrum antibiotic use on general pediatric wards. Infection. 2017;**45**(4):493-504. DOI: 10.1007/

Localio AR, Szymczak JE,

jama.2017.18715

s15010-017-1009-0

2018-1056

[65] Poole NM, Shapiro DJ, Fleming-Dutra KE, Hicks LA, Hersh AL, Kronman MP. Antibiotic prescribing for children in United States emergency departments: 2009-

2014. Pediatrics. 2019;**143**(2): e20181056. DOI: 10.1542/peds.

peds.2013-3260

[53] Ibrahim AA. Identification of iha and kpsMT virulence genes in *Escherichia coli* isolates with urinary tract infection in Iraqi patients. Indian Journal of Natural Sciences.

2019;**52**(9):16675-16682

10.4236/oju.2013.32024

2012.16656

10.1086/524891

[54] Al-Jebouri MM, Mdish SA.

Antibiotic resistance pattern of bacteria isolated from patients of urinary tract infections in Iraq. Open Journal of Urology. 2013;**3**(2):124-131. DOI:

[55] Lafi SA, Alkarboly AA, Lafi MS. Bacterial urinary tract infection in adults, hit district Anbar governorate, west of Iraq. Egyptian Academic Journal of Biological Sciences, G. Microbiology. 2012;**4**(1):21-26, 10.21608/EAJBSG.

[56] Spellberg B, Guidos R, Gilbert D, Bradley J, Boucher HW, Scheld WM, et al. Infectious Diseases Society of America. The epidemic of antibiotic-resistant infections: A call to action for the medical community from the Infectious Diseases Society of America. Clinical Infectious Diseases. 2008;**46**(2):155-164. DOI:

[57] Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance. BMC Infectious

Diseases. 2014;**14**(1):13. DOI: 10.1186/1471-2334-14-13

[58] Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;**128**(6): 1053-1061. DOI: 10.1542/peds.

[59] Lee GC, Reveles KR, Attridge RT, Lawson KA, Mansi IA, Lewis JS, et al. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Medicine. 2014;**12**(1):96. DOI:

10.1186/1741-7015-12-96

**216**

2011-1337

[66] Aljanaby AA, Alfaham QM. Phenotypic and molecular characterization of some virulence factors in multidrug resistance *Escherichia coli* isolated from different clinical infections in Iraq. American Journal of Biochemistry and Molecular Biology. 2017;**7**:65-78. DOI: 10.3923/ ajbmb.2017.65.78

[67] Al-Delaimi MS, Nabeel M. Early onset neonatal sepsis: Bacteriological antimicrobial susceptibility study in Duhok Province, Iraq. Journal of University of Babylon for Pure and Applied Sciences. 2019;**27**(3):196-212

[68] ABDULRAHMAN IS, SAADI AT. Bacterial isolates and their antimicrobial resistance patterns in neonatal sepsis recorded at Hevi Teaching Hospital in Duhok City/Kurdistan Region of Iraq. Duhok Medical Journal. 2019;**13**(2):84-95

[69] Saadi AT, Garjees NA, Rasool AH. Antibiogram profile of septic meningitis among children in Duhok, Iraq. Saudi Medical Journal. 2017;**38**(5):517

[70] Al-mousawi MR. Bacterial profile and antibiogram of bacteremic children in Karbala city, Iraq. Karbala Journal of Pharmaceutical Sciences. 2016;**11**:131-139

[71] Raham TF, Abood AM. Bacterial profile and antimicrobial susceptibility in neonatal sepses, Al-Alwyia Pediatric Teaching Hospital in Baghdad. Al-Kindy College Medical Journal. 2017;**13**(2):21-25

[72] Ibrahim SA, Rahma S. Microbiological profile of neonatal septicemia. Iraqi Postgraduate Medical Journal. 2012;**11**:13-18

[73] Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic

analysis for the Global Burden of Disease Study 2010. The Lancet. 2012;**380**(9859):2095-2128. DOI: 10.1016/S0140-6736(12)61728-0

[74] Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study. The Lancet. 2013;**382**(9888):209-222. DOI: 10.1016/S0140-6736(13)60844-2

[75] Livermore DM, Woodford N. The β-lactamase threat in Enterobacteriaceae. Pseudomonas and Acinetobacter. Trends in Microbiology. 2006;**14**(9):413-420. DOI: 10.1016/j. tim.2006.07.008

[76] Al-Marzoqi AH, Aziz HW, Dulaimi TH. Genotype, phenotype and virulence genes markers in *Escherichia coli*: Molecular characterization and antimicrobial susceptibility associated with Diarrhoea among children in Babil province, Iraq. International Journal of Biochemistry, Bioinformatics a nd Biotechnology Studies. 2019;**4**(1):11-20

[77] Al-Dahmoshi HO, Al-Yassari AK, Al-Saad NF, Al-Dabagh NN, Al-Khafaji NS, Mahdi RK, et al. Occurrence of AmpC, MBL, CRE and ESBLs among diarrheagenic *Escherichia coli* recovered from Infantile Diarrhea, Iraq. Journal of Pharmaceutical and Biomedical Sciences. 2015;**5**:189-195

[78] Al-Saadi ZH, Tarish AH, Saeed EA. Phenotypic detection and antibiotics resistance pattern of local serotype of *E. coli* O157: H7 from children with acute diarrhea in Hilla city/Iraq. Journal of Pharmaceutical Sciences and Research. 2018;**10**(3):604-609

[79] Abdul-hussein ZK, Raheema RH, Inssaf AI. Molecular diagnosis of diarrheagenic *E. coli* infections among the pediatric patients in Wasit Province, Iraq. Journal of Pure and Applied Microbiology. 2018;**12**(4):2229-2241

[80] Shamki JA, Al-Charrakh AH, Al-Khafaji JK. Detection of ESBLs in enteropathogenic *E. coli* (EPEC) isolates associated with infantile diarrhea in Kut City. Medical Journal of Babylon. 2012;**9**(2):403-412

[81] Khalil ZK. Isolation and identification of different diarrheagenic (DEC) *Escherichia coli* pathotypes from children under five years old in Baghdad. Iraqi Journalof Community Medicine. 2015;**28**(3):126-132

[82] Hassan JS. Antimicrobial resistance patterns of *Escherichia coli* O157: H7 isolated from stool sample of children. Iraqi Journal of Medical Sciences. 2015; **13**(3):259-264

[83] Jameel ZJ, Al-Assie AH, Badawy AS. Isolation and characterization of enteroaggregative *Escherichia coli* among the causes of bacterial diarrhea in children. Tikrit Journal of Pure Science. 2018;**20**(4):30-37

[84] Yaqoob MM, Mahdi KH, Al-Hmudi HA, Mohammed-Ali MN. Detection of rotavirus a and *Escherichia coli* from diarrhea cases in children and Coliphage characterization. International Journal of Current Microbiology and Applied Sciences. 2016;**5**(4):68-83. DOI: 10.20546/ ijcmas.2016.504.011

[85] AL-Shuwaikh AM, Ibrahim IA, Shwaikh RM. Detection of *E. coli* and rotavirus in diarrhea among children under five years old. Iraqi Journal of Biotechnology. 2015;**14**(1):85-92

[86] Alsherees HA, Ali SN. A preliminary occurrence of extended-spectrum and AmpC Beta-lactamases in clinical isolates of enteropathogenic *Escherichia coli* in Najaf, Iraq. bioRxiv. 2019;**1**:512731. DOI: 10.1101/512731

[87] Hemalatha R, Ramalaxmi BA, Swetha E, Balakrishna N, Mastromarino P. Evaluation of vaginal pH for detection of bacterial vaginosis. The Indian Journal of Medical Research. 2013;**138**(3):354

[88] Al-Khaqani MM, Alwash MS, Al-Dahmoshi HO. Investigation of phylogroups and some virulence traits among cervico-vaginal *Escherichia coli* (CVEC) isolated for female in Hilla City, Iraq. Malaysian Journal of Microbiology. 2017;**13**(2):132-138

[89] Paniagua-Contreras GL, Monroy-Pérez E, Solis RR, Cerón AB, Cortés LR, Alonso NN, et al. O-serogroups of multi-drug resistant cervicovaginal *Escherichia coli* harboring a battery of virulence genes. Journal of Infection and Chemotherapy. 2019;**25**(7):494-497. DOI: 10.1016/j.jiac. 2019.02.004

[90] Chen LF, Chopra T, Kaye KS. Pathogens resistant to antibacterial agents. Infectious Disease Clinics. 2009;**23**(4):817-845. DOI: 10.1016/j. idc.2009.06.002

[91] Al-Mayahie SM. Phenotypic and genotypic comparison of ESBL production by vaginal *Escherichia coli* isolates from pregnant and non-pregnant women. Annals of Clinical Microbiology and Antimicrobials. 2013;**12**(1):7. DOI: 10.1186/1476-0711-12-7

[92] Ullauri A, Smith A, Espinel M, Jimenez C, Salazar C, Castrillon R. WHO ear and hearing disorders survey: Ecuador national study 2008-2009. Conference Papers in Science. 2014;**2014**:13. DOI: 10.1155/2014/847526.847526

[93] Fauci AS, Kasper DL, Longo DL, et al. Harrison's Principles of Internal Medicine. 17th ed. New York, NY, USA: McGraw-Hill; 2008

[94] Yiengprugsawan V, Hogan A. Ear infection and its associated risk factors, comorbidity, and health service use in Australian children. International

**219**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

> [101] Al-Fayyadh ZH, Turkie AM, Al-Mathkhury HJ. New mutations in GyrA gene of *Escherichia coli* isolated form Iraqi patients. Iraqi Journal of Science. 2017;**58**(2B):778-788. DOI:

10.24996.ijs.2017.58.2B.1

[102] Alfatlawi AS, Alsaidi MA,

Almaliky NK, Alsherees HA. Molecular characterization of extended spectrum â-lactamases (ESBLs) producing *Escherichia coli* isolated from Cholecystitis. EurAsian Journal of BioSciences. 2019;**13**(1):113-120

[103] Al-Rawazq HS, Mohammed AK, Hussein AA. Etiology and antibiotic sensitivity for otitis media in a central pediatric teaching hospital. Iraqi Medical Journal. 2013;**59**(2):84-90

[104] Kumar A, Jayachandran L, Kumar S. Antimicrobial susceptibility pattern in chronic suppurative otitis media patient in a tertiary care hospital. Value in Health. 2016;**19**(7):A845-A846

[105] Alsaimary IE, Alabbasi AM, Najim JM. Impact of multi drugs resistant bacteria on the pathogenesis of chronic suppurative otitis media. African Journal of Microbiology Research. 2010;**4**(13):1373-1382

[106] Ibrahim II. Bacteriological study of chronic suppurative otitis media among patients attending Tikrit Teaching Hospital for the year 2013. The Medical Journal of Tikrit. 2015;**20**(2):15-28

[107] Neamah AS. Detection of bacterial pathogens causing a chronic suppurative otits media and study of antibiotic susceptibility in Iraqi patients. International Journal of Research in Pharmaceutical Sciences. 2019;**10**(3): 2567-2571. DOI: 10.26452/ijrps.

v10i3.1511

[108] Wajid AR, Alwan SK.

Bacteriological and genetic study on *Escherichia coli* causing acute calculus cholecystitis for diabetes patients

Journal of Pediatrics. 2013;**2013**:7. DOI:

[95] Llor C, Bjerrum L. Antimicrobial resistance: Risk associated with antibiotic overuse and initiatives to reduce the problem. Therapeutic Advances in Drug Safety. 2014;**5**(6):229-241. DOI:

10.1155/2013/963132.963132

10.1177/2042098614554919

[97] Okike IO, Johnson AP, Henderson KL, Blackburn RM, Muller-Pebody B, Ladhani SN, et al. Incidence, etiology, and outcome of bacterial meningitis in infants aged< 90 days in the United Kingdom and Republic of Ireland: Prospective, enhanced, national population-based surveillance. Clinical Infectious Diseases. 2014;**59**(10):e150-e157. DOI:

10.1093/cid/ciu514

ESP-0015-2015

2015.05.017

2017.00685

[98] Kim KS. Human meningitisassociated *Escherichia coli*. EcoSal Plus. 2016;**7**(1):1-25. DOI: 10.1128/ecosalplus.

[99] Liu J, Yan Q, Luo F, Shang D, Wu D, Zhang H, et al. Acute

cholecystitis associated with infection of Enterobacteriaceae from gut microbiota. Clinical Microbiology and Infection. 2015;**21**(9):851-8e1. DOI: 10.1016/j.cmi.

[100] Kujiraoka M, Kuroda M, Asai K, Sekizuka T, Kato K, Watanabe M, et al. Comprehensive diagnosis of bacterial infection associated with acute cholecystitis using metagenomic approach. Frontiers in Microbiology. 2017;**8**:685. DOI: 10.3389/fmicb.

v12i3.18

[96] Afolabi OA, Salaudeen AG, Ologe FE, Nwabuisi C, Nwawolo CC. Pattern of bacterial isolates in the middle ear discharge of patients with chronic suppurative otitis media in a tertiary hospital in North central Nigeria. African Health Sciences. 2012;**12**(3):362-367. DOI: 10.4314/ahs. *Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

Journal of Pediatrics. 2013;**2013**:7. DOI: 10.1155/2013/963132.963132

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

[87] Hemalatha R, Ramalaxmi BA,

[88] Al-Khaqani MM, Alwash MS, Al-Dahmoshi HO. Investigation of phylogroups and some virulence traits among cervico-vaginal *Escherichia coli* (CVEC) isolated for female in Hilla City, Iraq. Malaysian Journal of Microbiology.

2017;**13**(2):132-138

2019.02.004

idc.2009.06.002

10.1186/1476-0711-12-7

10.1155/2014/847526.847526

McGraw-Hill; 2008

[89] Paniagua-Contreras GL,

Cortés LR, Alonso NN, et al.

Monroy-Pérez E, Solis RR, Cerón AB,

O-serogroups of multi-drug resistant cervicovaginal *Escherichia coli* harboring a battery of virulence genes. Journal of Infection and Chemotherapy. 2019;**25**(7):494-497. DOI: 10.1016/j.jiac.

[90] Chen LF, Chopra T, Kaye KS. Pathogens resistant to antibacterial agents. Infectious Disease Clinics. 2009;**23**(4):817-845. DOI: 10.1016/j.

[91] Al-Mayahie SM. Phenotypic and genotypic comparison of ESBL production by vaginal *Escherichia coli* isolates from pregnant and non-pregnant women. Annals of Clinical Microbiology and Antimicrobials. 2013;**12**(1):7. DOI:

[92] Ullauri A, Smith A, Espinel M, Jimenez C, Salazar C, Castrillon R. WHO ear and hearing disorders survey: Ecuador national study 2008-2009. Conference Papers in Science. 2014;**2014**:13. DOI:

[93] Fauci AS, Kasper DL, Longo DL, et al. Harrison's Principles of Internal Medicine. 17th ed. New York, NY, USA:

[94] Yiengprugsawan V, Hogan A. Ear infection and its associated risk factors, comorbidity, and health service use in Australian children. International

Swetha E, Balakrishna N, Mastromarino P. Evaluation of vaginal pH for detection of bacterial vaginosis. The Indian Journal of Medical Research. 2013;**138**(3):354

the pediatric patients in Wasit Province, Iraq. Journal of Pure and Applied Microbiology. 2018;**12**(4):2229-2241

[81] Khalil ZK. Isolation and identification

[82] Hassan JS. Antimicrobial resistance patterns of *Escherichia coli* O157: H7 isolated from stool sample of children. Iraqi Journal of Medical Sciences. 2015;

[83] Jameel ZJ, Al-Assie AH, Badawy AS. Isolation and characterization of

enteroaggregative *Escherichia coli* among the causes of bacterial diarrhea in children. Tikrit Journal of Pure Science.

of different diarrheagenic (DEC) *Escherichia coli* pathotypes from children under five years old in Baghdad. Iraqi Journalof Community Medicine.

[80] Shamki JA, Al-Charrakh AH, Al-Khafaji JK. Detection of ESBLs in enteropathogenic *E. coli* (EPEC) isolates associated with infantile diarrhea in Kut City. Medical Journal of Babylon.

2012;**9**(2):403-412

2015;**28**(3):126-132

**13**(3):259-264

2018;**20**(4):30-37

ijcmas.2016.504.011

DOI: 10.1101/512731

[84] Yaqoob MM, Mahdi KH,

Al-Hmudi HA, Mohammed-Ali MN. Detection of rotavirus a and *Escherichia coli* from diarrhea cases in children and Coliphage characterization. International Journal of Current Microbiology and Applied Sciences. 2016;**5**(4):68-83. DOI: 10.20546/

[85] AL-Shuwaikh AM, Ibrahim IA, Shwaikh RM. Detection of *E. coli* and rotavirus in diarrhea among children under five years old. Iraqi Journal of Biotechnology. 2015;**14**(1):85-92

[86] Alsherees HA, Ali SN. A preliminary occurrence of extended-spectrum and AmpC Beta-lactamases in clinical isolates of enteropathogenic *Escherichia coli* in Najaf, Iraq. bioRxiv. 2019;**1**:512731.

**218**

[95] Llor C, Bjerrum L. Antimicrobial resistance: Risk associated with antibiotic overuse and initiatives to reduce the problem. Therapeutic Advances in Drug Safety. 2014;**5**(6):229-241. DOI: 10.1177/2042098614554919

[96] Afolabi OA, Salaudeen AG, Ologe FE, Nwabuisi C, Nwawolo CC. Pattern of bacterial isolates in the middle ear discharge of patients with chronic suppurative otitis media in a tertiary hospital in North central Nigeria. African Health Sciences. 2012;**12**(3):362-367. DOI: 10.4314/ahs. v12i3.18

[97] Okike IO, Johnson AP, Henderson KL, Blackburn RM, Muller-Pebody B, Ladhani SN, et al. Incidence, etiology, and outcome of bacterial meningitis in infants aged< 90 days in the United Kingdom and Republic of Ireland: Prospective, enhanced, national population-based surveillance. Clinical Infectious Diseases. 2014;**59**(10):e150-e157. DOI: 10.1093/cid/ciu514

[98] Kim KS. Human meningitisassociated *Escherichia coli*. EcoSal Plus. 2016;**7**(1):1-25. DOI: 10.1128/ecosalplus. ESP-0015-2015

[99] Liu J, Yan Q, Luo F, Shang D, Wu D, Zhang H, et al. Acute cholecystitis associated with infection of Enterobacteriaceae from gut microbiota. Clinical Microbiology and Infection. 2015;**21**(9):851-8e1. DOI: 10.1016/j.cmi. 2015.05.017

[100] Kujiraoka M, Kuroda M, Asai K, Sekizuka T, Kato K, Watanabe M, et al. Comprehensive diagnosis of bacterial infection associated with acute cholecystitis using metagenomic approach. Frontiers in Microbiology. 2017;**8**:685. DOI: 10.3389/fmicb. 2017.00685

[101] Al-Fayyadh ZH, Turkie AM, Al-Mathkhury HJ. New mutations in GyrA gene of *Escherichia coli* isolated form Iraqi patients. Iraqi Journal of Science. 2017;**58**(2B):778-788. DOI: 10.24996.ijs.2017.58.2B.1

[102] Alfatlawi AS, Alsaidi MA, Almaliky NK, Alsherees HA. Molecular characterization of extended spectrum â-lactamases (ESBLs) producing *Escherichia coli* isolated from Cholecystitis. EurAsian Journal of BioSciences. 2019;**13**(1):113-120

[103] Al-Rawazq HS, Mohammed AK, Hussein AA. Etiology and antibiotic sensitivity for otitis media in a central pediatric teaching hospital. Iraqi Medical Journal. 2013;**59**(2):84-90

[104] Kumar A, Jayachandran L, Kumar S. Antimicrobial susceptibility pattern in chronic suppurative otitis media patient in a tertiary care hospital. Value in Health. 2016;**19**(7):A845-A846

[105] Alsaimary IE, Alabbasi AM, Najim JM. Impact of multi drugs resistant bacteria on the pathogenesis of chronic suppurative otitis media. African Journal of Microbiology Research. 2010;**4**(13):1373-1382

[106] Ibrahim II. Bacteriological study of chronic suppurative otitis media among patients attending Tikrit Teaching Hospital for the year 2013. The Medical Journal of Tikrit. 2015;**20**(2):15-28

[107] Neamah AS. Detection of bacterial pathogens causing a chronic suppurative otits media and study of antibiotic susceptibility in Iraqi patients. International Journal of Research in Pharmaceutical Sciences. 2019;**10**(3): 2567-2571. DOI: 10.26452/ijrps. v10i3.1511

[108] Wajid AR, Alwan SK. Bacteriological and genetic study on *Escherichia coli* causing acute calculus cholecystitis for diabetes patients

in AL-Diwanyia City. International Journal. 2015;**3**(6):1374-1382

[109] van Koppen CJ, Hartmann RW. Advances in the treatment of chronic wounds: A patent review. Expert Opinion on Therapeutic Patents. 2015;**25**(8):931-937. DOI: 10.1517/13543776.2015.1045879

[110] Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: An update on the current knowledge and concepts. European Surgical Research. 2017;**58**(1-2):81-94. DOI: 10.1159/000454919

[111] Moet GJ, Jones RN, Biedenbach DJ, Stilwell MG, Fritsche TR. Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: Report from the SENTRY Antimicrobial Surveillance Program (1998-2004). Diagnostic Microbiology and Infectious Disease. 2007;**57**(1):7-13. DOI: 10.1016/j. diagmicrobio.2006.05.009

[112] Tourmousoglou CE, Yiannakopoulou EC, Kalapothaki V, Bramis J, Papadopoulos JS. Surgicalsite infection surveillance in general surgery: A critical issue. Journal of Chemotherapy. 2008;**20**(3):312-318. DOI: 10.1179/joc.2008.20.3.312

[113] Al-Abbas AK. Aerobic bacteria isolation from post-caesarean surgical site and their antimicrobial sensitivity pattern in Karbala city, Iraq. Iraq Medical Journal. 2017;**1**(4):94-98

[114] Lafi SA, Al-Shamarry M, Ahmed MS, Ahmed WI. Bacterial profile of infected traumatic wound and the antibiogram of predominant bacterial isolates using Viteck automated system in Ramadi Teaching Hospital, Iraq. Egyptian Academic Journal of Biological Sciences, G. Microbiology. 2018;**10**(1):69-76

[115] Abboud ZH, Al-Ghanimi NH, Ahmed MM. An insight into bacterial profile and antimicrobial susceptibility of burn wound infections in Kerbala, Iraq. Karbala Journal of Medicine. 2014;**7**(2):2023-2032

[116] Alkaabi SA. Bacterial isolates and their antibiograms of burn wound infections in Burns Specialist Hospital in Baghdad. Baghdad Science Journal. 2013;**10**(2):331-340

[117] Ali MR, Al-Taai HR, Al-Nuaeyme HA, Khudhair AM. Molecular study of genetic diversity in Escherichia coli isolated from different clinical sources. Biochemical and Cellular Archives. 2018;**18**(2):2553-2560

[118] Aljanaby AA, Aljanaby IA. Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City. Iraq-a three-year cross-sectional study. F1000Research. 2018;**7**(1157):1157-10.12688/ f1000research.15088.1

[119] Abdulqader HH, AT S. The distribution of pathogens, risk factors and their antimicrobial susceptibility patterns among post-surgical site infection in Rizgari Teaching Hospital in Erbil/Kurdistan Region/Iraq. Journal of Duhok University. 2019;**22**(1):1-0. DOI: 10.26682/sjuod.2019.22.1.1

[120] Ali FA, Merza EM, Aula TS. Antibiotic resistance among *Escherichia coli* isolated from different clinical samples in Erbil City. International Journal of Research Studies in Science, Engineering and Technology. 2017;**4**(10):12-21

[121] Ali FA. Distribution of CTX-M gene among *Escherichia coli* strains isolated from different clinical samples in Erbil City. Iraqi Journal of Biotechnology. 2018;**17**(1):78-90

[122] Al-Azawi ZH. Antimicrobial susceptibility patterns of aerobic

**221**

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

bacterial species of wound infections in Baquba General Teaching Hospital-Diyala. Diyala Journal of Medicine.

[123] Hussein NH. Genotypic detection of carbapenem-resistant *Escherichia coli* producing NDM-1 gene for the first time in Baghdad/Iraq. Journal of Global Pharma Technology. 2017;**9**(9):106-111

[124] ASK A-K, Albaayit A, Ibraheem OS, Abdul-Ilah HH. Molecular investigation of metallo-β-lactamase encoding gene in nosocomial carbapenemresistant Enterobacteriaceae in Iraqi Hospitals. The Eurasia Proceedings of Science, Technology, Engineering &

Mathematics. 2018;**2**:239-243

[125] Abas IJ, Al-Hamdani MA. New Delhi metallo-Β-lactamase 1 (Ndm-1) producing *Escherichia coli* in Basrah Hospitals, Iraq. European Journal of Biomedical. 2017;**4**(02):102-107

[126] Al-Hasnawy HH, Saleh RH, Hadi BH. Existence of a ESBL genes in *Escherichia coli* and *Acinetobacter baumannii* isolated from different clinical specimens. Journal of

2018;**10**(5):1112-1117

Pharmaceutical Sciences and Research.

2013;**4**(1):94-100

*Antibiotic Resistance among Iraqi Local* E. coli *Isolates DOI: http://dx.doi.org/10.5772/intechopen.92107*

bacterial species of wound infections in Baquba General Teaching Hospital-Diyala. Diyala Journal of Medicine. 2013;**4**(1):94-100

E. Coli *Infections - Importance of Early Diagnosis and Efficient Treatment*

profile and antimicrobial susceptibility of burn wound infections in Kerbala, Iraq. Karbala Journal of Medicine.

[116] Alkaabi SA. Bacterial isolates and their antibiograms of burn wound infections in Burns Specialist Hospital in Baghdad. Baghdad Science Journal.

2014;**7**(2):2023-2032

2013;**10**(2):331-340

[117] Ali MR, Al-Taai HR, Al-Nuaeyme HA, Khudhair AM. Molecular study of genetic diversity in Escherichia coli isolated from different clinical sources. Biochemical and Cellular Archives. 2018;**18**(2):2553-2560

[118] Aljanaby AA, Aljanaby IA. Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City. Iraq-a three-year cross-sectional study. F1000Research.

2018;**7**(1157):1157-10.12688/ f1000research.15088.1

10.26682/sjuod.2019.22.1.1

2017;**4**(10):12-21

[120] Ali FA, Merza EM, Aula TS. Antibiotic resistance among *Escherichia coli* isolated from different clinical samples in Erbil City. International Journal of Research Studies in

Science, Engineering and Technology.

[121] Ali FA. Distribution of CTX-M gene among *Escherichia coli* strains isolated from different clinical samples in Erbil City. Iraqi Journal of Biotechnology. 2018;**17**(1):78-90

[122] Al-Azawi ZH. Antimicrobial susceptibility patterns of aerobic

[119] Abdulqader HH, AT S. The distribution of pathogens, risk factors and their antimicrobial susceptibility patterns among post-surgical site infection in Rizgari Teaching Hospital in Erbil/Kurdistan Region/Iraq. Journal of Duhok University. 2019;**22**(1):1-0. DOI:

in AL-Diwanyia City. International Journal. 2015;**3**(6):1374-1382

[109] van Koppen CJ, Hartmann RW. Advances in the treatment of chronic wounds: A patent review. Expert Opinion on Therapeutic Patents.

[110] Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: An update on the current knowledge and concepts. European Surgical Research. 2017;**58**(1-2):81-94.

[111] Moet GJ, Jones RN, Biedenbach DJ, Stilwell MG, Fritsche TR. Contemporary

2015;**25**(8):931-937. DOI: 10.1517/13543776.2015.1045879

DOI: 10.1159/000454919

causes of skin and soft tissue infections in North America, Latin America, and Europe: Report from the SENTRY Antimicrobial Surveillance Program (1998-2004). Diagnostic Microbiology and Infectious Disease. 2007;**57**(1):7-13. DOI: 10.1016/j. diagmicrobio.2006.05.009

[112] Tourmousoglou CE,

Yiannakopoulou EC, Kalapothaki V, Bramis J, Papadopoulos JS. Surgicalsite infection surveillance in general surgery: A critical issue. Journal of Chemotherapy. 2008;**20**(3):312-318. DOI: 10.1179/joc.2008.20.3.312

[113] Al-Abbas AK. Aerobic bacteria isolation from post-caesarean surgical site and their antimicrobial sensitivity pattern in Karbala city, Iraq. Iraq Medical Journal. 2017;**1**(4):94-98

[114] Lafi SA, Al-Shamarry M, Ahmed MS, Ahmed WI. Bacterial profile of infected traumatic wound and the antibiogram of predominant bacterial isolates using Viteck automated system in Ramadi Teaching Hospital, Iraq. Egyptian Academic Journal of Biological Sciences, G. Microbiology.

[115] Abboud ZH, Al-Ghanimi NH, Ahmed MM. An insight into bacterial

**220**

2018;**10**(1):69-76

[123] Hussein NH. Genotypic detection of carbapenem-resistant *Escherichia coli* producing NDM-1 gene for the first time in Baghdad/Iraq. Journal of Global Pharma Technology. 2017;**9**(9):106-111

[124] ASK A-K, Albaayit A, Ibraheem OS, Abdul-Ilah HH. Molecular investigation of metallo-β-lactamase encoding gene in nosocomial carbapenemresistant Enterobacteriaceae in Iraqi Hospitals. The Eurasia Proceedings of Science, Technology, Engineering & Mathematics. 2018;**2**:239-243

[125] Abas IJ, Al-Hamdani MA. New Delhi metallo-Β-lactamase 1 (Ndm-1) producing *Escherichia coli* in Basrah Hospitals, Iraq. European Journal of Biomedical. 2017;**4**(02):102-107

[126] Al-Hasnawy HH, Saleh RH, Hadi BH. Existence of a ESBL genes in *Escherichia coli* and *Acinetobacter baumannii* isolated from different clinical specimens. Journal of Pharmaceutical Sciences and Research. 2018;**10**(5):1112-1117

## *Edited by Luis Rodrigo*

Gram-negative *Escherichia coli* (E. coli) bacteria are the most numerous commensal aerobic germs located in the human colon. Diarrhea caused by *E. coli* pathogenic strains is a major cause of death in developing countries, especially the sub-Saharan and South Asian areas. Some strains cause diarrhea, and all of them may produce an infectious disease. This book includes ten chapters covering the main aspects of infections related to *E. coli*, their pathogenic mechanisms, treatments, and resistance to diverse antibiotics.

Published in London, UK © 2020 IntechOpen © ChrisChrisW / iStock

E. Coli Infections - Importance of Early Diagnosis and Efficient Treatment

*E. Coli* Infections

Importance of Early Diagnosis

and Efficient Treatment

*Edited by Luis Rodrigo*