Does the beta-lactam matter? Nafcillin versus cefazolin for methicillin-susceptible staphylococcus aureus bloodstream infections

Corey C. Burrelli, Eleanor K. Broadbent, Alice Margulis, Graham M. Snyder, Howard S. Gold, Christopher McCoy, Monica V. Mahoney, Elizabeth B. Hirsch

Research output: Contribution to journalArticle

5 Scopus citations


Background: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. Objective: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. Methods: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ?72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, allcause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. Results: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-Treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-Treated patients. Conclusions: Among nafcillin-or cefazolin-Treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
Issue number6
StatePublished - Apr 1 2019



  • Acute interstitial nephritis
  • Acute kidney injury
  • Bacteremia
  • Hepatotoxicity
  • Staphylococcal penicillin

PubMed: MeSH publication types

  • Journal Article

Cite this

Burrelli, C. C., Broadbent, E. K., Margulis, A., Snyder, G. M., Gold, H. S., McCoy, C., Mahoney, M. V., & Hirsch, E. B. (2019). Does the beta-lactam matter? Nafcillin versus cefazolin for methicillin-susceptible staphylococcus aureus bloodstream infections. Chemotherapy, 63(6), 345-351.