Definitive cefazolin treatment for community-onset enterobacteriaceae bacteremia based on the contemporary CLSI breakpoint: Clinical experience of a medical center in southern Taiwan

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains debated. To assess its efficacy as a definitive agent, the 8-year cohort study consisted of 941 adults with monomicrobial cefazolin-susceptible EKP bacteremia, based on the CLSI criteria issued in 2019, was retrospectively established in a medical center. Based on the definitive antimicrobial prescription, eligible patients were categorized into the cefazolin (399 patients, 42.4%) and broader-spectrum antibiotic (BSA) (542, 57.6%) groups. Initially, fewer proportions of patients with fatal comorbidities (the McCabe classification) and the critical illness (a Pitt bacteremia score ≥4) at the onset and day 3 of the bacteremia episode were found in the cefazolin group, compared to the BSA group. After propensity-score matching, no significant difference of patient proportions between the cefazolin (345 patients) and BSA (345) groups was observed, in terms of the elderly, types and severity of comorbidities, bacteremia severity at the onset and day 3, major bacteremia sources, and the 15-day and 30-day crude mortality. In early outcomes, lengths of time to defervescence, intravenous (IV) antimicrobial administration, and hospitalization were similar in the two matched groups; lower costs of IV antimicrobial administration were observed in the cefazolin group. Notably, for late outcomes, lower proportions of post-treatment infections caused by antimicrobial-resistant pathogens (ARPs) and post-treatment mortality rates were evidenced in the cefazolin group. Conclusively, cefazolin is definitively efficacious and cost-effective for adults with community-onset cefazolin-susceptible EKP bacteremia in this one-center study, compared to BSAs. However, a prospective multicenter study should be conducted for external validation with other communities.