Is a Staphylococcus aureus (Staph aureus) infection that is resistant to penicillin but sensitive to oxacillin considered Methicillin-resistant Staphylococcus aureus (MRSA)?

Staphylococcus aureus Resistant to Penicillin but Sensitive to Oxacillin is NOT MRSA

No, a Staphylococcus aureus strain that is resistant to penicillin but sensitive to oxacillin is NOT considered MRSA (Methicillin-resistant Staphylococcus aureus). This pattern represents a methicillin-susceptible S. aureus (MSSA) strain that produces beta-lactamase.

Understanding S. aureus Resistance Patterns

Beta-lactamase Production vs. Methicillin Resistance

• Beta-lactamase production: Most S. aureus strains (approximately 80%) are resistant to penicillin due to production of beta-lactamase enzymes that break down the beta-lactam ring of penicillin 1. This is the most common resistance mechanism in S. aureus.
• Methicillin resistance: MRSA strains have a modified penicillin-binding protein (PBP2a) encoded by the mecA gene, which confers resistance to all beta-lactam antibiotics including penicillinase-resistant penicillins such as oxacillin, methicillin, nafcillin, and dicloxacillin 2.

Defining MRSA

MRSA is specifically defined as S. aureus that is resistant to oxacillin (or methicillin). As stated in the guidelines, "Methicillin-resistant S. aureus produces a penicillin-binding protein with reduced affinity for β-lactam antibiotics that is encoded by the mecA gene" 2. Since your isolate is sensitive to oxacillin, it cannot be classified as MRSA.

Clinical Implications

Treatment Approach for Penicillin-Resistant, Oxacillin-Sensitive S. aureus

For infections caused by S. aureus that is resistant to penicillin but sensitive to oxacillin:

1. First-line treatment options:

   • Penicillinase-resistant penicillins (oxacillin, nafcillin, dicloxacillin) are the antibiotics of choice 1
   • First-generation cephalosporins (cefazolin, cephalothin, cephalexin) are excellent alternatives 2, 1

2. For serious infections:

   • Nafcillin or oxacillin are preferred for serious MSSA infections 2
   • "Oxacillin, nafcillin, or cefazolin are preferred for the treatment of proven MSSA" 2

3. For less serious infections:

   • Oral options include dicloxacillin, cephalexin, or clindamycin (if susceptible) 1

Avoiding Common Pitfalls

1. Don't confuse penicillin resistance with methicillin resistance:

   • Approximately 80% of S. aureus isolates are resistant to penicillin but remain susceptible to oxacillin 1, 3
   • Only strains resistant to oxacillin/methicillin are considered MRSA

2. Don't use vancomycin unnecessarily:

   • Guidelines clearly state that vancomycin should be reserved for MRSA infections or patients with severe beta-lactam allergies 2
   • Beta-lactams (oxacillin, nafcillin, cefazolin) have superior outcomes compared to vancomycin for MSSA infections 2

3. Testing considerations:

   • Oxacillin susceptibility testing is the standard method for determining if a strain is MRSA 4
   • Some laboratories may use cefoxitin as a surrogate marker for oxacillin resistance

Conclusion

A S. aureus strain that is resistant to penicillin but sensitive to oxacillin is definitively classified as methicillin-susceptible S. aureus (MSSA), not MRSA. This resistance pattern is extremely common, representing the majority of S. aureus isolates, and these infections should be treated with penicillinase-resistant penicillins or first-generation cephalosporins rather than vancomycin or other MRSA-targeted antibiotics.