Retrospective Evaluation of the Association of Oxacillin MIC on Acute Treatment Outcomes with Cefazolin and Antistaphylococcal Penicillins in Methicillin-Susceptible Staphylococcus aureus Bacteremia

J Clin Microbiol. 2023 Apr 20;61(4):e0003923. doi: 10.1128/jcm.00039-23. Epub 2023 Mar 29.

Abstract

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Keywords: BORSA; MSSA bacteremia; antistaphylococcal penicillin; cefazolin; nafcillin; oxacillin.

MeSH terms

  • Aged
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Bacteremia* / drug therapy
  • Cefazolin* / adverse effects
  • Cefazolin* / pharmacology
  • Cefazolin* / therapeutic use
  • Female
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus* / drug effects
  • Middle Aged
  • Oxacillin* / adverse effects
  • Oxacillin* / pharmacology
  • Oxacillin* / therapeutic use
  • Retrospective Studies
  • Staphylococcal Infections* / drug therapy
  • Treatment Outcome

Substances

  • Oxacillin
  • Cefazolin
  • Anti-Bacterial Agents