A comparison of safety and outcomes with cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bloodstream infections

J Microbiol Immunol Infect. 2020 Apr;53(2):321-327. doi: 10.1016/j.jmii.2018.07.006. Epub 2018 Aug 18.


Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is a frequent cause of bloodstream infections (BSI). Treatment with nafcillin (NAF) has been preferred to cefazolin (CFZ). However, comparable outcomes have been found with CFZ with possibly lower risk for side-effects. This study compared safety and effectiveness of NAF versus CFZ for MSSA BSI.

Methods: This single center retrospective study evaluated adults admitted with MSSA BSI who received NAF or CFZ. Patients receiving ≥24 h of antibiotics were included for safety analyses. Patients receiving NAF or CFZ for ≥75% of a 14 day minimum treatment course were assessed for clinical effectiveness. The primary safety outcome was incidence of renal toxicity with multiple secondary safety endpoints. Clinical success was defined as symptom resolution, repeat negative cultures, lack of additional therapy for presumed failure, and lack of recurrence within 30 days.

Results: A total of 130 patients receiving NAF (n = 79) or CFZ (n = 51) were included for safety analysis. Of those, 90 met criteria for effectiveness assessment (NAF n = 40, CFZ n = 50). Baseline characteristics were well matched. NAF was associated with a higher incidence of nephrotoxicity compared to CFZ (25% vs. 2%, RR 1.31, 95% CI 1.15-1.5, p < 0.001), allergic reactions (p = 0.01) and a trend for hepatotoxicity (p = 0.08). Clinical success was achieved in 82% NAF and 94% CFZ treated patients (p = 0.1).

Conclusion: CFZ was associated with less nephrotoxicity and no difference in clinical success compared to NAF for MSSA BSI. A prospective study comparing NAF to CFZ for MSSA BSI should be conducted to elucidate differences in therapies.

Keywords: Bloodstream infections; Cefazolin; Methicillin-susceptible; Nafcillin; Staphylococcus aureus.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Cefazolin / adverse effects
  • Cefazolin / therapeutic use*
  • Endocarditis / microbiology
  • Female
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus
  • Middle Aged
  • Nafcillin / adverse effects
  • Nafcillin / therapeutic use*
  • Retrospective Studies
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Treatment Outcome
  • Vascular Grafting / adverse effects
  • Young Adult


  • Anti-Bacterial Agents
  • Nafcillin
  • Cefazolin