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Mechanisms of methicillin resistance in Staphylococcus aureus and methods for laboratory detection
1Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750.
Abstract:
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 beta-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 beta-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 beta-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 2a) include the microdilution minimum inhibitory concentration (MIC) test (with 2% NaCl supplemented broth), the oxacillin agar screen plate test (incorporating 6 micrograms/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 degrees C for a full 24 hours.
Insights
Methicillin resistance in Staphylococcus aureus is primarily due to PBP 2a. Reliable detection methods for MRSA include MIC, oxacillin agar screen, and NCCLS disk diffusion tests.
Area of Science:
- Microbiology
- Clinical Laboratory Science
- Antibiotic Resistance
Background:
- Staphylococcus aureus exhibits multiple mechanisms for methicillin resistance.
- The primary mechanism involves producing penicillin-binding protein 2a (PBP 2a), conferring resistance to beta-lactam antibiotics.
- Other mechanisms include borderline resistance (BORSA) and modified normal PBPs (MODSA), with less understood prevalence and clinical impact.
Purpose of the Study:
- To elucidate the mechanisms of methicillin resistance in Staphylococcus aureus.
- To highlight the role of PBP 2a as the principal mechanism.
- To identify reliable in vitro susceptibility testing methods for MRSA detection.
Main Methods:
- Describing PBP 2a production as the key resistance mechanism.
- Detailing the BORSA mechanism linked to beta-lactamase hyperproduction.
- Introducing the MODSA mechanism involving modified PBPs.
- Outlining validated in vitro susceptibility tests: MIC, oxacillin agar screen, and NCCLS disk diffusion.
Main Results:
- PBP 2a production confers resistance to methicillin, oxacillin, and other beta-lactams.
- BORSA and MODSA represent alternative, less characterized resistance pathways.
- Specific in vitro tests (MIC, oxacillin agar screen, NCCLS disk diffusion) are recommended for accurate MRSA detection.
Conclusions:
- PBP 2a is the most significant mechanism for methicillin resistance in Staphylococcus aureus.
- Accurate detection of MRSA is crucial for effective treatment.
- Standardized laboratory testing methods ensure reliable identification of resistant strains.