Is cefazolin effective against Methicillin-Sensitive Staphylococcus aureus (MSSA)?

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Last updated: October 11, 2025View editorial policy

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Cefazolin is Effective Against MSSA

Yes, cefazolin is effective against methicillin-sensitive Staphylococcus aureus (MSSA) and is considered an appropriate treatment option for MSSA infections. 1, 2

Evidence Supporting Cefazolin for MSSA

  • Cefazolin is FDA-approved for the treatment of serious infections due to Staphylococcus aureus, including beta-lactamase-producing strains (which includes MSSA) 1
  • The Infectious Diseases Society of America (IDSA) recommends cefazolin as an appropriate treatment option for pyomyositis caused by MSSA 2
  • Many experts regularly use cefazolin for S. aureus infections instead of nafcillin due to better drug tolerability and cost, particularly for MSSA infections 2
  • Cefazolin is specifically listed as a reasonable alternative in patients with a well-defined history of nonanaphylactoid reactions to penicillins (e.g., simple skin rash) who have MSSA infections 2

Comparative Effectiveness with Other Anti-MSSA Agents

  • A large retrospective cohort study found no significant difference in 30-day mortality between patients with MSSA bacteremia treated with flucloxacillin (an antistaphylococcal penicillin) versus cefazolin (10.7% vs 11.2%) 3
  • A systematic review and meta-analysis demonstrated that cefazolin was associated with significant reduction in mortality (OR 0.69) and clinical failure (OR 0.56) compared to antistaphylococcal penicillins for MSSA bacteremia 4
  • When comparing nafcillin/oxacillin with cefazolin for MSSA bacteremia, 30-day mortality was similar between groups, supporting cefazolin as an effective treatment option 5

Clinical Considerations When Using Cefazolin for MSSA

  • Cefazolin is often preferred over antistaphylococcal penicillins due to its better safety profile, with significantly lower rates of nephrotoxicity (OR 0.36) and hepatotoxicity (OR 0.12) 4
  • In cases of brain abscess resulting from MSSA infective endocarditis, guidelines recommend nafcillin instead of cefazolin due to concerns about CNS penetration 2
  • Although cefazolin may be more susceptible to β-lactamase–mediated hydrolysis than nafcillin in laboratory testing (known as the cefazolin inoculum effect), the clinical significance of this observation remains uncertain 2

Important Distinction Between MSSA and MRSA

  • While cefazolin is effective against MSSA, it is important to note that methicillin-resistant S. aureus (MRSA) strains are uniformly resistant to cefazolin 1, 6
  • When empiric coverage for both MSSA and MRSA is needed before culture results are available, appropriate options include vancomycin, daptomycin, or linezolid, not cefazolin 6
  • Once culture results confirm MSSA, therapy can be narrowed to cefazolin as an appropriate targeted therapy 2, 7

Dosing and Administration

  • For serious MSSA infections, cefazolin is typically administered intravenously at doses of 0.5-1g every 8 hours, with adjustments based on infection severity and renal function 2, 1
  • Cefazolin achieves high serum concentrations (approximately 185 mcg/mL peak after 1g IV dose) with a serum half-life of approximately 1.8 hours 1

In summary, cefazolin is an effective and often preferred treatment option for MSSA infections due to its proven efficacy, favorable safety profile, and cost advantages compared to antistaphylococcal penicillins.

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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