Three distinctly different mechanisms of methicillin resistance have been described in Staphylococcus aureus. The best-documented and probably most important mechanism is production of a unique, low affinity penicillin-binding protein, PBP 2a Strains possessing PBP 2a are resistant to methicillin, oxacillin, and probably all other currently available b-lactam antibiotics. Two additional mechanisms of reduced susceptibility to methicillin have been described. Borderline resistance (BORSA) to the semi-synthetic penicillins has been attributed to the hyperproduction of normal staphylococcal b-lactamase. A third mechanism has recently been advanced that describes an intermediate level of resistance to methicillin due to production of modified, normal PBPs with reduced affinity for b-lactams (MODSA). Little is known regarding the prevalence or clinical significance of the BORSA and MODSA strains. The most reliable in vitro susceptibility test methods for detecting MRSA (strains possessing PBP 2,) include the microdilution minimum inhibitory concentration (MIC) test (with 2% NaCl supplemented broth), the oxacillin agar screen plate test (incorporating 6 ug/ml oxacillin in 4% NaCl supplemented agar), and the National Committee for Clinical Laboratory Standards (NCCLS) disk diffusion test with oxacillin. All three methods use direct inoculum preparation and incubation of tests at 35°C for a full 24 hours.

Typing systems for differentiating among strains of methicillin-resistant Staphylococcus aureus (MRSA) can be valuable tools for the epidemiologist and the clinician. Specific criteria for evaluating such systems are typeability, reproducibility, and discriminatory power. An ideal typing system also would be rapid, inexpensive, technically simple, and readily available. Systems based on the detection of phenotypic variations include antimicrobial susceptibility testing, bacteriophage typing, multilocus enzyme electrophoresis, and electrophoretic methods such as protein eletrophoresis and immunoblotting. Systems that directly detect genotypic variations include plasmid profile analysis, restriction enzyme analysis of plasmid DNA, restriction enzyme analysis of chromosomal DNA, Southern blot analysis of specific restriction fragment length polymorphisms, and pulse field gel electrophoresis. in general, the more widely available typing systems based on phenotypic assays and plasmid analysis have limitations in typeability and/or discriminatory power.The chromosomal DNA-based techniques, although promising, are unproven approaches still under active investigation.

The mechanism of methicillin resistance confers resistance to all available B-lactam antibiotics; consequently, B-lactam antibiotics have no role in therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections. Vancomycin remains the drug of choice. Teicoplanin and daptomycin are two investigational antibiotics related to vancomycin in structure and in spectrum of activity. In clinical trials employing relatively low doses, neither was as effective as vancomycin. Trials at higher doses are on-going. Quinolones, ciprofloxacin in particular, have been used successfully to treat infections caused by MRSA; however, the usefulness of quinolones may be limited by the tendency of resistance to emerge during therapy. Quinolones probably should be used only in combination with another active agent, such as rifampin, when treating serious infections caused by MRSA. Other agents may be active in vitro against MRSA, but clinical data showing their effectiveness are lacking. Rifampin combination regimens appear most effectively to eradicate colonization with MRSA.