**4. Infection control**

Sequence type 131 (ST131) is a pathogenic clone of *E. coli* and it also frequently expresses a hydrolytic β-lactamase enzyme called CTX-M-type and has rapidly disseminated worldwide. *E. coli* expressing CTX-M-type enzymes containing ESBLs have been increasingly seen in the community [12, 22–26]. Residency of a long-term care facility has been recognized as a prominent risk factor for acquisition of ESBL infections in the community. Various studies have also identified ESBL bacteremia as an independent risk factor from exposure to fluoroquinolones, first-generation cephalosporins, and finally, a previously known colonization history with an ESBL [25, 27]. Patients are 57% more likely to die from bloodstream infections associated with ESBL-producing *Enterobacteriaceae* than those with bloodstream infections caused by a non

In a study by Ha et al. [28], they concluded that significant risk factors associated with ESBLproducing *E. coli* bacteremia were prior treatment with fluoroquinolones and cephalosporins, as previous studies have also demonstrated. Moreover, recent surgery, liver disease, and immunosuppressant use were also deemed as significant risk factors. The study resulted in an overall 30-day mortality rate of 14.9%. As described previously, the mortality rate was higher in patients with ESBL-producing *E. coli* than in those without ESBL bacteremia (22.1 vs. 12.2%; *P* = 0.02). A multivariate analysis in this study demonstrated an independent risk factor for mortality (odds ratio = 3.01, 95% confidence interval 1.45–6.28; *P* = 0.003) for ESBL bacteremia

*P. aeruginosa* is a common cause of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections. *P. aeruginosa* can easily adapt to the environment it inhabits, this ability can lead to colonization, and ultimately invade the human host defenses and cause serious infections. According to the CDC, approximately 7.1% of all healthcare-associated infections in the United States are caused by *P. aeruginosa*. This organism was the second most common cause of pneumonia in the hospital setting, and the third most common cause of Gram-negative bloodstream infections [5]. Kollef et al. recently conducted a global prospective epidemiological study on the prevalence of *P. aeruginosa* causing Ventilator-associated pneumonia (VAP). They concluded that global

In 2013, the CDC's National Healthcare Safety Network (NSHN) reported that 8% of all healthcare-associated infections are caused by *P. aeruginosa*. Among these 8% reported to the NSHN, approximately 13% were considered severe healthcare-associated infections caused by MDR *P. aeruginosa*. By definition, MDR is resistance to at least three different antibiotics classes (mainly antipseudomonal penicillins, aminoglycosides, cephalosporins, and carbapenems). Each year, approximately 51,000 healthcare-associated *P. aeruginosa* infections occur in the United States (according to the CDC). Of these infections, more than 13% are classified as multidrug-resistant (MDR) *P. aeruginosa* and contribute roughly to 400 deaths per year [5].

The true prevalence of multidrug-resistant *P. aeruginosa* is not well established, mainly because there are considerable different definitions used in the literature. Upon reviewing many studies, they tend to report on both MDR and "pan-drug resistant" *P. aeruginosa* infections. In 2011, a new standardized definition was proposed, which classified *Pseudomonas* as MDR, XDR, or pan drug-resistant (PDR) bacteria. MDR as described above is resistant to at least one antibiotic

incidence was 4.1%, and did not differ among countries significantly [29].

ESBL-producing strain [26].

82 Contemporary Topics of Pneumonia

[26, 28].

Environmental reservoirs may be unrecognized as the culprit for outbreaks or ongoing sporadic transmission. Recent studies suggest that the risk of acquiring multidrug-resistant pathogens such as *Acinetobacter* spp., *Pseudomonas* spp., vancomycin-resistant Enterococcus (VRE), MRSA, or *C. difficile* is increased if a new patient admission is placed in a room previously occupied by a colonized or infected patient with one of the above pathogens [33–38]. "Terminal cleans" have been utilized for multidrug-resistant Gram-negative organisms and may be integrated with infection control measures, along with surveillance to limit the horizontal transmission of multidrug-resistant organisms.

Environmental survival times of infectious pathogens [39]:


Environmental surfaces are routinely disinfected in hospitals based on infection control policies and procedures. Several factors dictate the type and frequency for these cleanings such as surface characteristics, intensity of people traffic, clinical risk, and patient turnover. Following a patient discharge that was known to be colonized or infected with a multidrugresistant pathogen, a terminal or deep cleaning may be performed. The cleaning regimen is usually tailored with a disinfectant and strength of choice for that particular pathogen. This process usually includes initial removal of all detachable objects from the room, such as bedding and curtains. The terminal clean also includes wiping down any ventilation components on the ceiling or lighting. Finally, all other surfaces and sites are cleaned downward toward the floor level, and all equipment and items that were removed from the room are wiped over with disinfectant before returning to the room. Automated technologies have been recently introduced and may offer enhanced decontamination. Although these technologies are automated they do not replace routine daily cleaning [39].

to report their antimicrobial use and resistance patterns into the National Healthcare Safety Network (NSHN). This tracking system is the nation's most widely used for healthcare-associated infection. This process will enable the CDC to benchmark hospitals and assess antimicrobial use by measuring the Standardized Antimicrobial Administration Ratio (SAAR). The measurement is a ratio of observed-to-expected (O-to-E). Ratio values greater than 0, and a value of 1.0 suggests equivalency between the observed and predicted antimicrobial use. Values above 1.0 may indicate statistically significant excessive antimicrobial use [44]. In addition to the CDC, many hospital regulatory agencies such as the Joint Commission and CMS will be enforcing this element as part of complying with antimicrobial stewardship program

Multidrug-Resistant Gram-Negative Pneumonia and Infection in Intensive Care Unit

http://dx.doi.org/10.5772/intechopen.69377

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Microorganisms are tenacious at survival, they have been on the Earth for billions of years, and their sole existence is based on their ability to adapt to the environment. This ability for survival despite the introduction of antibiotics is best described antimicrobial resistance. The mechanisms of antimicrobial resistance are as follows: (a) enzymatic degradation of antibiotics via hydrolytic enzymes, (b) alteration of bacterial proteins or target sites, and (c) changes in membrane permeability to antibiotics either by penetration or by expulsion of the actual antibiotic from within the bacteria. Antibiotic resistance can be either plasmid or chromosomal mediated. One of the most important mechanisms of resistance to beta-lactams is enzymatic hydrolysis of the ring structure resulting in inactivity [45]. The chromosomal β-lactamases expression can either be depressed or induced or by the exposure to β-lactam antibiotics. Overcoming resistance to β-lactam antibiotics includes the coadministration of inhibitors to protect the ring structure, and the development of new antibiotics that are stable against enzymatic degradation. By adding a β-lactamase inhibitor to a β-lactam antibiotic, this allows the β-lactam to avoid enzymatic hydrolysis and perform its bactericidal effects.

a) Efflux pumps (especially overexpression), which pump the drug out of the cell.

b) Changes in porin protein channels in outer membrane (decreased number or channel

d) Enzymatic hydrolysis, i.e., beta-lactamases in Enterobacteriaceae, and nonfermentative

e) Change in binding affinity of antibiotic for target, i.e., penicillin-binding proteins, DNA

Bacterial resistance to β-lactam antibiotics as mentioned earlier is mediated via β-lactamases; this mode is the primary mechanism of resistance. Ambler molecular classification is used to classify β-lactamases and is based on the amino acid sequence and divides the class into four

mandates [42, 43].

**6. Mechanisms of resistance**

The following are examples of resistance [45]:

c) Circumvent metabolic pathways.

Gram-negatives (Acinetobacter).

topoisomerases, and ribosomal targets.

charge alteration), which decreases drug uptake.

In the following study, terminal cleaning, combined with standard infection control polices resulted in 70–40% reduction in patients colonized with MDR *Enterobacteriaceae*. These results were attributed to the overall combined intervention. Universal decolonization has been conducted in many ICUs; particularly, after the results of a landmark trial called REDUCE MRSA [33]. Huang et al. concluded that routine ICU practice and universal decolonization was more effective than targeted decolonization or screening [40]. The universal decolonization was effective at reducing rates of MRSA and bloodstream infection from any pathogen. In the treatment group, the number needed to treat (to prevent one) bloodstream infection was per 99 patients. Other technologies have been explored such automated decontamination devices which include peroxide and UV light. As mentioned earlier, these automated technologies could possibly offer some improvement, but they should not replace routine daily cleaning. Common pitfalls for these techniques include additional training of staff, management and personnel oversight, logistical complexities, and costs of equipment. Future studies are warranted to evaluate overall costs versus benefits [39].

The Affordable Care Act in 2015 mandated that the hospital-acquired condition (HAC) reduction program reduce hospital payments by 1% for hospitals performing at the lowest ranked 25% with regard to hospital-acquired conditions. These conditions include Catheter Associated Urinary Tract Infections (CAUTI) and Central Line Associated Bloodstream Infections (CLABSI). As of 2017, CMS has also added both CDI and MRSA to the program. Given that hospitals are now accountable for these conditions, it is imperative that they have robust infection control policies and procedures and have also successfully implemented antimicrobial stewardship programs as defined by the Joint Commission Medication Management (MM) Standard MM.09.01.01 [41–43].
