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

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.