How can I differentiate methicillin‑susceptible Staphylococcus aureus (MSSA) from methicillin‑resistant Staphylococcus aureus (MRSA) using the antimicrobial susceptibility report?

Differentiating MSSA from MRSA on Antimicrobial Susceptibility Reports

The key distinction between MSSA and MRSA on a sensitivity report is susceptibility to methicillin or its surrogate markers: MRSA will show resistance to oxacillin, nafcillin, or cefoxitin, while MSSA will show susceptibility to these agents. 1, 2

Primary Laboratory Markers

Cefoxitin Disk Test (Preferred Screening Method)

• Cefoxitin (30 μg) disk diffusion is the standard method for identifying MRSA in clinical laboratories 3
• This test detects the mecA gene product (PBP 2a) more reliably than direct oxacillin testing 4
• Results interpretation:
  • Resistant to cefoxitin = MRSA
  • Susceptible to cefoxitin = MSSA

Oxacillin/Methicillin Testing

• Oxacillin susceptibility testing can be used, though cefoxitin is preferred 4
• Oxacillin MIC ≤2 μg/mL = MSSA
• Oxacillin MIC >2 μg/mL = MRSA 5

Nafcillin Susceptibility

• Nafcillin susceptibility patterns mirror oxacillin 1
• Susceptible strains indicate MSSA and should be treated with antistaphylococcal penicillins 2

Secondary Distinguishing Features on Susceptibility Reports

Broader Resistance Patterns

MRSA typically demonstrates multidrug resistance beyond just β-lactam antibiotics 6, 3:

• MRSA shows significantly higher resistance rates to:

  • Clindamycin (45.7% resistant in MRSA vs. lower in MSSA) 3
  • Ciprofloxacin (64.7% resistant in MRSA) 3
  • Erythromycin (54.3% resistant in MRSA) 3
  • Tetracycline (58.4% resistant in MRSA) 3

• MSSA typically shows better susceptibility to:

  • Trimethoprim-sulfamethoxazole (99% susceptible in community-associated MSSA) 7
  • Clindamycin (96% susceptible in community-associated MSSA) 7
  • Fluoroquinolones (76% susceptible in community-associated MSSA) 7

Universal Susceptibilities

• Both MSSA and MRSA remain universally susceptible to vancomycin 6, 3
• Both are typically susceptible to linezolid and daptomycin 5, 8

Critical Clinical Pitfalls

Heteroresistance

• Some MRSA strains may appear phenotypically susceptible to β-lactams on standard testing but carry the mecA gene 4
• These mecA-positive, phenotypically susceptible strains are functionally resistant and should be treated as MRSA 4

Inducible Clindamycin Resistance

• Hospital-associated MRSA shows inducible clindamycin resistance in 50% of cases vs. only 8.4% in community-associated MRSA 7
• MRSA demonstrates 21.4% inducible clindamycin resistance overall 3
• This requires D-test evaluation if clindamycin therapy is considered

Penicillin Susceptibility Testing Unreliability

• Even if rare staphylococcal strains appear penicillin-susceptible, current laboratory screening procedures are unreliable 1
• All S. aureus should be treated with antistaphylococcal penicillins (nafcillin/oxacillin) rather than penicillin G, regardless of reported penicillin susceptibility 1

Practical Algorithm for Report Interpretation

1. Look first at cefoxitin or oxacillin susceptibility:

   • Resistant = MRSA → Use vancomycin, daptomycin, or linezolid 1, 5
   • Susceptible = MSSA → Use nafcillin, oxacillin, or cefazolin 2

2. Verify with resistance pattern:

   • Multiple drug resistances suggest MRSA 6, 3
   • Narrow resistance profile suggests MSSA 7

3. Check vancomycin MIC if MRSA:

   • MIC >2 μg/mL requires alternative therapy 5
   • Target trough 15-20 μg/mL if using vancomycin 9, 2