PCR Detection of Methicillin Resistance in Staphylococcus aureus
Yes, the simultaneous detection of S. aureus DNA and a methicillin-resistance gene (mecA or mecC) by PCR is sufficient to diagnose MRSA and should guide immediate antimicrobial therapy. 1
Diagnostic Validity of PCR-Based MRSA Detection
The Clinical and Laboratory Standards Institute explicitly states that molecular detection of mecA (or mecC) serves as the gold standard for defining methicillin resistance in staphylococci when S. aureus is also identified. 1 This approach is validated because:
- PCR accurately identifies both S. aureus (via species-specific genes like nuc or femA) and methicillin resistance (via mecA gene detection) directly from positive blood cultures 1, 2
- The mecA gene encodes PBP2a, the penicillin-binding protein responsible for methicillin resistance, making its presence definitively diagnostic 1
- Multiplex PCR assays demonstrate 97-100% sensitivity and 99-100% specificity for MRSA detection compared to conventional methods 3, 2
Clinical Application and Treatment Implications
When PCR detects both S. aureus and mecA:
- Treat immediately as MRSA without waiting for phenotypic susceptibility testing 1
- Initiate appropriate anti-MRSA therapy with vancomycin (15-20 mg/kg IV every 8-12 hours), daptomycin (10 mg/kg/day IV), or linezolid (600 mg twice daily) 1, 4
- PCR results are available within 4-6 hours versus 48-72 hours for conventional culture-based methods, significantly reducing time to targeted therapy 1, 3
Important Caveats
Rare Discordance Scenarios
In the extremely rare case of genotypic-phenotypic discordance (mecA-positive but phenotypically susceptible), the Clinical and Laboratory Standards Institute recommends treating the isolate as methicillin-resistant. 1 This occurs in less than 1% of cases. 5
The mecC Variant
- Some MRSA strains carry mecC instead of mecA, a homolog that also confers methicillin resistance 1
- Standard PCR assays must include primers for both mecA and mecC to avoid false-negative results 6
- mecC prevalence varies geographically but remains rare in most regions (absent in some countries like Turkey) 6
Advantages Over Conventional Testing
The rapid molecular approach provides:
- Reduction in time to appropriate therapy from 37-50 hours to 5-18 hours for MSSA cases (allowing de-escalation from vancomycin) 1
- Reduction in time to MRSA-targeted therapy from 24-36 hours to 6-11 hours 1
- Improved mortality outcomes, as each day of delayed culture clearance increases attributable mortality 1
Practical Implementation
When interpreting PCR results:
- S. aureus-positive + mecA-positive = MRSA → Use anti-MRSA antibiotics 1, 2
- S. aureus-positive + mecA-negative = MSSA → Use beta-lactams (nafcillin, oxacillin, cefazolin) 1
- Coagulase-negative staphylococci + mecA-positive = Methicillin-resistant CoNS → Consider clinical significance and treat if pathogenic 2
The combination of rapid molecular testing with antimicrobial stewardship intervention (direct communication to primary service) further reduces time to optimal therapy. 1