Clinical implications of cefazolin inoculum effect and β-lactamase type on methicillin-susceptible Staphylococcus aureus bacteremia.

Abstract

Cefazolin is a common antibiotic for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Type A or C β-lactamase-producing MSSA frequently shows the cefazolin inoculum effect (CIE). However, the clinical implication of the CIE for MSSA bacteremia is obscure. MSSA bacteremic patients treated with cefazolin were included in a retrospective cohort study. The blaZ gene of the isolates was sequenced to identify the type of β-lactamase. The patients whose isolates showed a ≥4-fold increase in cefazolin, the minimal inhibitory concentration (MIC) at the high inoculum (∼5×10(7) CFU/ml), were assigned to the CIE-positive group and the remainder to the CIE-negative group. Treatment failure was assessed at 12 weeks after cefazolin was initiated. A total of 113 MSSA bacteremic patients were included. Among the 113 isolates, 57.5% showed the CIE and 77.9% carried the blaZ gene; type A β-lactamase was 15.0% and type C was 40.7%. Persistent bacteremia was more common in the CIE-positive group (9% vs. 0%, p=0.04). Treatment failure rates were higher in the CIE-positive group with high bacterial burden infection, but the difference was not significant (48% vs. 25%, p=0.13). There was no significant difference of failure between groups with high-inoculum MIC ≥16 and ≤1 μg/ml (13% vs. 5%, p=0.31). In the multivariable analysis, underlying cardiovascular diseases, pneumonia, osteoarticular infections, and endocarditis were significant risk factors for treatment failure and the CIE was not significantly associated with treatment failure. The CIE might be associated with persistent bacteremia if cefazolin is used for MSSA bacteremia with a high burden of infections. However, the sites of infections are more important factors for the clinical outcome than the CIE.