**1. Introduction**

Antimicrobial resistance (AMR) is a global threat and is of a major public health concern globally [1]. AMR is defined as a state when microbes including bacteria, virus, fungi and parasites no longer respond to the drugs thereby increasing their risk of disease spread, causing severe illness and death (**Figure 1**) [2].

AMR can spread through 'horizontally' by different transformation method in which bacteria transfer a part of their genetic material with another bacteria, or the

### **Figure 1.**

*Graphical abstract showing AMR spread in rural India.*

spread may be 'vertically' where AMR genes are continuously transferred from one generation to the next and so on [3].

Although inappropriate and irrational use of antimicrobial agents in animals has been considered to be responsible for the emergence of drug-resistant pathogens [4].

Making the treatment of infectious disease with antimicrobial agents challenging contributing to the community with respect to infectious disease burden. World Health Organization (WHO) declared AMR as one of the top 10 public threats as a result this may lead to high disease load in India which is considered as maximum in the world [2]. The current situation is reflected by high rate of AMR against several infectious diseases including urinary tract infections (UTIs), soft tissue infections, diarrhea and sepsis. In addition the rapid spread of penicillin-resistant bacteria (Methicillin resistant *Staphylococcus aureus* (MRSA) superbugs are also alarming.

Many sustainable development goals framework in the rural India have included "AMR indicator" that monitors the frequency of bloodstream infections caused due to antimicrobial resistant organisms including *S. aureus (S. aureus). S. aureus* is a part of human skin flora and a common infection causing agent implicated in acute food poisoning episodes, scalded skin syndrome,impetigo, cellulitis, folliculitis toxic shock syndrome, and furuncles [5]. Reports in the literature suggest that patients with MRSA infections are 64% more likely to die due to unresponsiveness of beta-lactam antibiotics and vancomycin which are the drug of choice for treating various ailments produced by Staphylococcus [6].

Notably *S. aureus* infections have raised concerns these days due to increasing antimicrobial resistance (MRSA). In rural India the antibiotic usage in humans and in the livestock is high with no regulation on the usage of antibiotics which may be a leading cause of antimicrobial resistance [7]. Indian Network for surveillance of Antimicrobial Resistance (INSAR) along with WHO monitors AMR and its magnitude in India. Their major goal is to focus on AMR patterns of various antimicrobial resistant microorganisms including *S. aureus*.

*Antimicrobial Resistance in Staphylococci Special Emphasis on Methicillin Resistance… DOI: http://dx.doi.org/10.5772/intechopen.99830*

Rural community of India is dependent on companion livestock for their livelihood as livestock sector is major part in developing their socio-economic status. Livestock sector found to be responsible for about 6% to the gross domestic product (GDP) and 25% to the agricultural GDP of India [7, 8].

The dairy farming is a common practice which have a positive impact on the rural system [9]. Thus, the rural population is much exposed to acquisition of AMR from livestock. Most reports on AMR in human associated with companion livestock have been confined to enteric organisms. However, staphylococcal infections in livestock is palpably common in India which include staphylococcal infections viz. Bovine mastitis, wound infections and udder impetigo ultimately affecting the public health and economy [10].

The present report attempts to review the problem of AMR in Staphylococci in livestock animals and their possible transmission to human.

## **2. Antimicrobial resistance**

AMR occurs when pathogens change genetically over time so as to become resistant to antimicrobials. As a result, the antimicrobials become ineffective against microorganisms and the infections remain persistent in the body. Antimicrobials including antibiotics, antivirals, antifungals and antiparasitic are the form of drugs that used to prevent and treat respective infections in humans and animals. Microorganisms that develop AMR are sometimes referred to as "superbugs" [2].

AMR has developed as one of the foremost community well-being issue of the 21st century that threaten the health care system due to ineffective prevention and treatment measures against wide range of infections. The problem of AMR in bacteria is of great concern. Over several decades, bacteria are involved in common or severe infections along with resistance towards variety of antimicrobials used against variety of ailments caused by bacteria. It is quite difficult to underestimate the impact of AMR in terms of death rate and community health. Thus, a muchneeded action plan is required to estimate such developing global issue in health care settings as well as in the community.

In natural environment, antibiotic resistance occurs in antibiotic-exposed microorganisms over time. Susceptible bacteria are killed or inhibited under the bactericidal effect of antibiotics. However, microorganisms that have acquired antibiotic-resistant genes due to overuse, misuse and unsuitable (inadequate dosing inappropriate choices and weak acceptance of updated treatment guidelines) of antibiotics have a greater chance to survive and proliferate. This is how the antimicrobial resistance is facilitated. In a developing country like India, the excessive prescription by general practitioners due to similarity of clinical presentations in viral or bacterial etiology can be seen. In addition the diagnostic uncertainty, selfmedication and easy availability of antimicrobial drugs without a proper prescription is also have significant root cause in the inappropriate use of antibiotics [11].

### **2.1 Methicillin resistance** *S. aureus* **in human**

*S. aureus* has been reported as a significant pathogen of human subjects. Sir Alexander Ogston in 1880 firstly reported *S. aureus* as a major cause of wound suppuration. Skinner and Keefer provided the first evidence of *S. aureus* virulence in 1941 and reported 82% mortality rate due to *S. aureus* associated bacteremia. In 1960s, the introduction of β-lactam antibiotic revolutionized the clinical care system and decreased the mortality rate associated with *S. aureus* bacteremia markedly to 27% with its widespread usage [12, 13].

*S. aureus* is one of the most studied troublesome resident and notorious pathogen in the human skin. *S. aureus* is a member of genus Staphylococcus that consist of fifteen different strains with differential molecular data. The status of *S. aureus* as a commensal is highly controversial. Several reports suggest that at around 30% of the nasal cavity flora of humans carries *S. aureus* or coagulase positive *S. aureus* (CoPS) species [14, 15]. Asymptomatic healthy humans and animals could harbor multiple species and strains of staphylococci [16].

Methicillin was the first semisynthetic penicillinase-resistant penicillin introduced in 1961 for treatment of Staphylococcal infections. Soon after its introduction in clinical practice, reports of methicillin-resistant isolates encountered [17].

The dissemination of MRSA have a great impact on both rural society as well as on hospital settings [18]. with all evidences centers for diseases control (CDC) declared methicillin resistant as a consequential issue to public wellness [19]. Thus, knowledge regarding the mechanisms of methicillin resistance in *S.aureus* has great clinical and epidemiological importance.

Based on the antimicrobial susceptibility, MRSA exists in three forms i.e., community associated MRSA (CA MRSA); health care-associated MRSA (HA-MRSA) and livestock associated MRSA (LA-MRSA). The difference among all the three forms lies with their clinical features, molecular biology, antibiotic susceptibility pattern and treatment measures. CA-MRSA and HA-MRSA are the major form of infections. MRSA infections are endemic in India with an incidence rate of 25% in Western regions and 50% in South regions of India. However in India, CA-MRSA and LA-MRSA are more prevalent as compared to HA-MRSA. The major concern arises when the isolation rate of CA MRSA enhanced as these species lead to replace HA-MRSA among hospitality settings which in turn build infection preventive and control measures slighter effective and significant for reducing the isolation rates of MRSA in healthcare settings [20].

### **2.2 LA- MRSA**

The problem of methicillin resistant *S. aureus* associated with livestock is long recognized as LA-MRSA. A-MRSA is entirely different from the other two forms (Hospital acquired, and community acquired). However LA-MRSA is not associated with health-related concerns in animals, but it also affects human health if they are in contact with them. In India most of the population is dependent on livestock for their livelihood. Transmission of the methicillin resistant strains from animals to humans or vice versa and may lead to any infection.

The MRSA carriers (animals/humans) are considered as colonized. Harbored animals may pretend as MRSA pools. Persons who lives and comes in direct interaction with MRSA colonized livestock are at high risk of being harbored/colonized by LA-MRSA. This could be a leading cause of transmission of LA-MRSA to further subjects subsequently transmitting the disease in the community at very high extent [21].

LA-MRSA is grouped under zoonoses which is described as the naturally spread infections among "animals and humans" as per the definition by WHO expert committee, 1951. Based on the prevalent direction of transmission between humans and other vertebrates, 'zoonosis' is also considered as 'Anthropozoonosis' which is suggestive for the transmission of humans to animals. Colonization with LA-MRSA may result into various ailments among human as well as in animals.

MRSA is commonly associated with bovine mastitis and the first evidence of mastitis was recorded in dairy cattle in 1972. Since then, MRSA colonization has been reported in the domestic animals namely cows, dogs, horses, sheep, cats and pigs [22, 23]. Mastitis with *S. aureus* features the genotypes of hugely deviating

### *Antimicrobial Resistance in Staphylococci Special Emphasis on Methicillin Resistance… DOI: http://dx.doi.org/10.5772/intechopen.99830*

*mecA* gene, termed as *mecC* in a type XI SCCmec or ST398 MRSA with SCC*mec* types IV andV. The appearance of LS MRSA (MRSA*mecC* and CC398) carrying SCC*mec* types (IV and V) and *mecC* were isolated firstly from pigs afterwards in cattle, pet animals, lineal calves, chickens, horses, fauna and human subjects in adjacent vicinity in those tame livestock's [24]. The clone type ST-398 of LA-MRSA, is commonly detected in European and North American countries whereas ST-9 primarily in the Asian region. The SCCmec type IV and V have to be found as co-resistant towards tetracycline and lincosamide, which are moderated by *tet* and *erm* genes successively [25]. A special attention is needed to be given for the patients with SARS-CoV requiring ventilation support as this pandemic may result into markedly rise in MRSA infection [26].

Due to highest milk production yield in India in the world and involved in dairy production results in high prevalence of LA-MRSA. The zoonotic potential of many bacterial strains among humans and animals are increasingly being isolated in Europe with much of the industrialized world [27, 28]. Most of the cattle's in India shared same residential premises with humans hence are more prone to transfer MRSA to the humans who are in close contact with them. The detection of MRSA special emphasis to cattle with sub/clinical mastitis is highly concerned from public health sentiments as the cattle looks all right even if they are colonized with reservoirs with MRSA [27, 28]. However the situation is something different in India as livestock's are considered as a family members due to their same residential premises sharing.

In addition to the above Jully G Tiwari from Assam showed that all the family members of the dairy farm worker were suffering from an identical type of cutaneous disease as of the bovine infection. The antibiotic susceptibility pattern (AST) of all biotype A strains from animals' origin were found alike to that of the biotype A strains isolated from the humans associated with the day care activities with the animals. In addition to the previous findings the rate of resistance towards commonly used antimicrobial agents in different ailments were also found markedly higher among the biotype C strains originated from human subjects than the biotype C strains from the animal origin. In addition many strains from animals and human origins revealed similar antimicrobial susceptibility testing patterns against various tested antimicrobial agents. [29]

The prevalence of Staphylococcus species was found in the mastitis cases of dairy animals as 45% (95% CI, 39–50%) based on the previous meta-analysis in India reported by Krishnamoorthy et al. [30].
