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Significance of MRSA in Nosocomial Infections

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Significance of MRSA in Nosocomial Infections International Journal of Applied Science www.ijas.org.uk Review Article Significance of MRSA in nosocomial Infections Dr. Javid Ahmad Bhat*1 and Dr Rajesh Tenguria2 1Division of Microbiology, M.V.M College Bhopal, M.P. India 2Department of Microbiology, M.V.M. College Bhopal, M.P. India. A R T I C L E I N F O A B S T R A C T Received 25 June 2014 Received in revised form 29 June 2014 Staphylococcus aureus is one of the most virulent microbial pathogen Accepted 04 July 2014 amongst gram positive bacteria to cause nosocomial and community acquired infections. An additional concern is the emergence and Keywords: dissemination of nosocomial organisms with increased resistance to MRSA, antimicrobial agents. Such microbes include methicillin resistant VRE, Nosocomial, S.aureus (MRSA), S.epidermidis, vancomycin resistant Enterococci mecA gene, (VRE) and VISA. The development of vaccines and drugs that prevent CA-MRSA. and cure bacterial infections was one of the twentieth century’s major contributions to human longevity and quality of life. Antibacterial agents are amongst the most commonly prescribed drugs of any kind worldwide. Used appropriately, these drugs are lifesaving however, their indiscriminate use drives up the cost of health care leading to a plethora of side effects and drug interactions and fosters the emergence of bacterial resistance rendering previously valuable drugs useless. Corresponding author: Division of Microbiology, M.V.M College Bhopal, M.P. India © 2014 International Journal of Applied Science- All rights reserved E-mail address: [email protected] INTRODUCTION Staphylococcus aureus is one of the Staphylococcus aureus is universal in most common and important pathogen, distribution found in pus, boils, abscess, skin, responsible for the majority of nosocomial throat, nasophrynx, oral mucosa, soil, sewage, infections. S.aureus is an opportunistic milk and water. They are gram positive cocci bacterium, normally, part of the human micro- arranged singly ranging from 1µm in diameter; flora but, attacks immediately when the immune pairs, tetrads and short chains but appear system of the host becomes susceptible. Even predominantly in grape like clusters. The cell though S.aureus can be found in different parts wall is composed of peptidoglycan and teichoic of the body but anterior nares are the principal acid3,4. ecological sites in humans1. A study had reported nasal carriage as a major risk factor for Mechanism of antibiotic resistance S.aureus infection that differs from person to person. It had been reported that 20% of the Penicillin resistance healthy individuals carry S.aureus persistently, 60% intermittently and 20% never carry History and epidemiology S.aureus2. The mortality of patients with S. aureus bacteremia in the pre-antibiotic era exceeded Bhat__________________________________________________________ ISSN: 2394-9988 80%, and over 70% developed metastatic cassette chromosome mec (SCCmec), harboring infections5. The introduction of penicillin in the the mecA gene and other resistance early 1940s dramatically improved the prognosis determinants. Methicillin resistance is mediated of patients with staphylococcal infection. by production of an altered penicillin binding However, as early as 1942, penicillin-resistant protein PBP-2a encoded by the mecA staphylococci were recognized, first in hospitals gene12,14,15-17. and subsequently in the community6. By the late Methicillin, like all penicillins exerts its 1960s, more than 80% of both community and battle by jamming the proteins called penicillin hospital-acquired staphylococcal isolates were binding protein (PBPs) which are liable for the resistant to penicillin. This pattern of resistance, construction and protection of the bacterial cell first emerging in hospitals and then spreading to wall. S.aureus resistant strains acquired a new the community, is now a well-established pattern protein called PBP2a (Figure 1b) which was not that recurs with each new wave of antimicrobial barren by methicillin and could restore the other resistance7. PBPs, thus, allowing the continued existence of S.aureus in the company of methicillin. PBP2a Mechanism of resistance is encoded by the gene mecA, which is the Staphylococcal resistance to penicillin is trademark of MRSA. As different to the mediated by blaZ, the gene that encodesβ- penicillinase gene mecA, it does not live on a lactamase (Figure 1a). This predominantly plasmid but on the chromosome fixed in a large extracellular enzyme, synthesized when movable genetic element called Staphylococcal staphylococci are exposed to β-lactam chromosome cassette mec or SCCmec 18. The antibiotics, hydrolyzes the β-lactam ring, occurrence of PBP2a means MRSA is not only rendering the β-lactam inactive. The gene blaZ opposing to methicillin but, moreover to all β- is under the control of two adjacent regulatory lactam antibiotics together with synthetic genes, the anti-repressor blaR1 and the repressor penicillins, cephalosporins and carbapenems. blaI 8. Recent studies have demonstrated that the Various methicillin resistant isolates had signaling pathway responsible for β-lactamase been reported with alterations in their synthesis requires sequential cleavage of the PBPs19,20,13. These isolates had been termed regulatory proteins BlaR1 and BlaI. Following moderately resistant S.aureus (MODSA). These exposure to β-lactams, BlaR1, a transmembrane isolates are not so ubiquitous in nature with low sensor-transducer, cleaves itself9,10. A study put resistance and without any clinical significance. forward that the cleaved protein functions as a It had been reported that isolates which protease that cleaves the repressor BlaI, directly produce large amounts of penicillinase or indirectly (an additional protein, BlaR2, may (penicillinase hyper-producers) may express low be involved in this pathway) and allows blaZ to level resistance under some test conditions21,22. synthesize enzyme11. These isolates had been referred to as borderline oxacillin resistant S.aureus (BORSA). There are Methicillin resistance no reports of failure of treatment with Staphylococcus aureus is a dynamic and penicillinase resistant penicillins in infections adaptable bacterium that has an incredible talent with such isolates and animal model to attain antibiotic resistance. Methicillin experiments indicate that their clinical resistant Staphylococcus aureus (MRSA) strains significance is doubtful23. Methicillin was the had rapidly emerged during 1960 and became a first penicillinase resistant penicillin used in 60s major problem in hospitals immediately after the and was recognized at that time as the most methicillin was introduced in 1959. At that time reliable agent for routine susceptibility testing, those nosocomial MRSA strains were highly though methicillin is now a day’s not used in multidrug resistant (MDR) but, many being treatment. That’s why; resistant strains were susceptible only to glycopeptides12-14. termed methicillin resistant S.aureus (MRSA). The genome of methicillin resistant Later, oxacillin resistant S.aureus (ORSA) came staphylococci contains a 21-67kb heterologous into existence after the use of oxacillin as an mobile genetic element termed staphylococcal alternative to methicillin in susceptibility tests. IJAS [1][1]2014 027-036 Bhat__________________________________________________________ ISSN: 2394-9988 Vancomycin resistance in Staphylococcus aureus which result in trapping of more and more It had been recorded that MRSA vancomycin molecules in the peptidoglycan infections are difficult to treat as compared to layers before they could reach to the cytoplasmic MSSA infections if, they are located at membrane where the synthesis of peptidoglycan anatomical sites because, at those sites antibiotic takes place33- 35. penetration is very less24. Vancomycin was the first glycopeptide MECHANISM OF PATHOGENESIS AND antibiotic that was introduced into clinical VIRULENCE FACTORS practice in 1958 after it was isolated in the mid 1950s25. Vancomycin had been the drug of Staphylococci are opportunistic choice for treatment of staphylococcal organisms that require following steps to start an nosocomial infections especially MRSA infection in its host such as inoculation and local throughout the world for the last 20 years. colonization of tissue surfaces, invasion, evasion Vancomycin is the second most common of the host response, and metastatic spread to 36 antibiotic used in hospitals throughout the invade the host and cause infection . A breach world, about 16 tons of the vancomycin is being in cutaneous or mucosal barriers is essential for used every year. Only 8 clinical vancomycin initiation of infection. resistant S.aureus (VRSA) isolates had been S.aureus expresses many potential isolated to date, all in the USA and mostly from virulence factors: (1) Surface proteins that the state of Michigan26. However, recent reports promote colonization of host tissues (2) Invasins proved some sort of concern regarding that promote bacterial spread in tissues vancomycin27. The first clinical vancomycin (leukocidin, kinases, hyaluronidase) (3) Surface intermediate resistant S.aureus (VISA) with a factors that inhibit phagocytic engulfment minimum inhibitory concentration (MIC) of (capsule, Protein-A) (4) Biochemical properties 8mg l-1 was documented in 1996 while, as the that enhance their survival in phagocytes first hetero vancomycin intermediate resistant (carotenoids, catalase production); (5) S.aureus (hVISA) with an MIC range
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