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Overview of MRSA
MRSA first reported in the 1960s in the hospital setting. The last several years has seen the rise of a Community based strain in various parts of the US. Genetic typing suspects the CA-MRSA has arisen from MSSA strains in the community rather than nosocomial MRSA. CA-MRSA mainly causes purulent skin/soft-tissue infections.
Mechanisms of Resistance
Beta-Lactamase with the use of PCN, S. aureus began to develop resistance via chromosomal and plasmidmediated betalactamases The enzyme cleaves the beta-lactam ring
Mechanisms of Resistance
In 1959, methicillin, a semisynthetic, betalactamase resistant PCN was introduced. By the early 1960s, MRSA had appeared. Resistance is mediated by the mecA gene, which is part of the mobile genomic element Staphylococcal Chromosomal Cassette (SCCmec). mecA gene expression produces an altered penicillin binding protein (PBP 2a).
They bind to proteins responsible for bacterial cell wall synthesis by transpeptidation (peptidase enzymes, aka penicillin binding proteins) If PBP is altered, then the antibiotic cannot inhibit cell wall formation and is rendered resistant.
Mechanisms of Resistance
There are four types of SCCmec, each with a varying array of drug resistance. SCCmec II and III is found in many nosocomial MRSA strains. These chromosomes harbor other antibiotic-resistance genes conferring resistance to aminoglycosides, tetracyclines, erythromycin and clindamycin. CA-MRSA carries SCCmec IV which only carries the mecA gene.
CA-MRSA has shown variability in its resistance to erythromycin by two mechanisms, one of which can be transferred to clindamycin.
1. Efflux pump - encoded by msrA gene; confers resistance of e-mycin, but not clindamycin 2. erm gene - erythromycin ribosomal methylase; mutation to clinda resistance may develop during clinda therapy
The D test - place a pair of erythromycin and clindamycin disks on a plated dish. Flattening of the clindamycin zone confers a positive test, i.e. inducible clinda resistance
CA-MRSA with inducible clindamycin resistance varies widely by region. Fewer than 10% of cases in Texas, Memphis and Baltimore, but more than 80% to 90% in Chicago and Minnesota have this property. At Texas Childrens Hospital, 7% of isolates are clindamycin resistant.
Mechanism of Virulence
CA-MRSA contain a unique virulence factor Panton-Valentine leukocidin (PVL). This cytotoxin destroys leukocytes and inflicts severe tissue damage, i.e. necrotic skin lesions and severe necrotizing pneumonia in both children and adults. PVL is not seen in hospital acquired MRSA. The combination of mecA and PVL gene creates a superadaptable Staph capable of spreading rapidly through the community.
Approach to Therapy
Principles of management:
Obtain specimens for culture of all skin infections Drain purulent collections and provide thorough wound care Know the organism resistance patterns for the community Make reliable plans for reassessment
Approach to Therapy
Is the infection suspected to severe or nonsevere? What can I empirically treat with until I have culture-proven MRSA?
Approach to Treatment
dicloxacillin, cephalexin, augmentin or clindamycin bactrim - avoid if suspecting skin infection by other pathogens, specifically group A Streptococcus Clindamycin if D-test is negative, bactrim, minocycline and linezolid
Culture-proven MRSA:
multiple infections in patient or within household proven S. aureus colonization No active S. aureus infections (acute episode has resolved)
Apply mupirocin intranasally twice daily for 5 to 10 days. All household members should be treated at same time.
Conclusion
CA-MRSA strain is unique from nosocomial MRSA in its mechanism of resistance, virulence factors and propensity for skin and soft tissue infections. Be aware of local patterns of antibiotic resistance for MRSA. CA-MRSA infection in the outpatient setting begin empiric therapy with either clindamycin or bactrim until culture results return. Consider decolonization when appropriate.
Bibliography
Siberry, G., Fighting a Rising Tide of MRSA Infection in the Young, Contemporary Pediatrics, July 1, 2005. Boyce, J., Epidemiology; prevention; and control of MRSA, UpToDate, 2005. Rybak, M., Community Associated MRSA - A Review, Pharmacotherapy 25(1):74-85, 2005.