Is Staphylococcus aureus (Staph aureus) that is resistant to penicillin, erythromycin, and clindamycin but sensitive to flucloxacillin, cefazolin, and sulfamethoxazole (sulfonamide) considered Methicillin-Resistant Staphylococcus aureus (MRSA) or Methicillin-Susceptible Staphylococcus aureus (MSSA)?

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Last updated: September 26, 2025View editorial policy

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Staphylococcus aureus Susceptibility Classification: MSSA

The Staphylococcus aureus isolate that is resistant to penicillin, erythromycin, and clindamycin but sensitive to flucloxacillin, cefazolin, and sulfamethoxazole is definitively classified as Methicillin-Susceptible Staphylococcus aureus (MSSA).

Explanation of Classification

The key determinant for classifying S. aureus as MRSA or MSSA is its susceptibility to methicillin or methicillin-equivalent antibiotics:

  • Flucloxacillin sensitivity: This is the critical finding that confirms MSSA status. Flucloxacillin is an isoxazolyl penicillin (anti-staphylococcal penicillin) that would not be effective against MRSA 1.

  • Cefazolin sensitivity: Further confirms MSSA status, as cefazolin (a first-generation cephalosporin) is effective against MSSA but not MRSA 1.

  • Penicillin resistance: This is common in both MSSA and MRSA due to beta-lactamase production. Approximately 80% of all S. aureus strains are resistant to penicillin regardless of methicillin susceptibility status 2.

Resistance Pattern Explanation

The resistance pattern observed in this isolate is typical for MSSA:

  • Penicillin resistance: Due to beta-lactamase production, which is present in most S. aureus strains 2.

  • Erythromycin and clindamycin resistance: This represents a specific resistance mechanism (often erm gene-mediated) that affects macrolides and lincosamides but does not confer methicillin resistance 3.

  • Sulfamethoxazole sensitivity: This is common in MSSA but can also be seen in some MRSA strains, particularly community-acquired MRSA 4.

Clinical Implications

The classification of this isolate as MSSA has important treatment implications:

  • First-line treatment options: For serious infections, flucloxacillin or cefazolin would be appropriate first-line therapies 1, 5.

  • Alternative options: For patients with penicillin allergies, sulfamethoxazole would be an effective alternative based on the susceptibility pattern 4.

  • Avoid ineffective antibiotics: Penicillin, erythromycin, and clindamycin should not be used despite the MSSA classification due to the specific resistance pattern of this isolate 3.

Common Pitfalls to Avoid

  1. Not distinguishing between penicillin and methicillin resistance: Many S. aureus strains are penicillin-resistant due to beta-lactamase production but remain susceptible to methicillin/flucloxacillin (MSSA) 2.

  2. Assuming all multi-resistant S. aureus are MRSA: Multi-drug resistance can occur in MSSA strains as well, particularly to antibiotics like erythromycin and clindamycin 3.

  3. Overlooking the definitive test: Susceptibility to flucloxacillin (or oxacillin/methicillin) is the definitive test for determining MSSA vs MRSA status, regardless of other resistance patterns 1.

By definition, this S. aureus isolate is MSSA because it remains susceptible to flucloxacillin, which is the key determinant in distinguishing between MSSA and MRSA.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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