Ceftolozane, formally
CXA-101, is a new antipseudomonal
cephalosporin that is also active in vitro against Enterobacteriaceae but is vulnerable to extended-spectrum β-lactamases (ESBLs). The addition of
tazobactam is intended to broaden coverage to most ESBL-producing Escherichia coli and Klebsiella
pneumonia as well as other Enterobacteriaceae. The in vitro activities of
ceftolozane-tazobactam combinations against 67 clinically and molecularly characterized ESBL-producing isolates were examined by checkerboard MIC testing to evaluate their potential clinical feasibility and to assess the optimal
tazobactam concentrations to be used in MIC determinations of
ceftolozane. Isolates included those from E. coli (n = 32), K. pneumoniae (n = 19), Enterobacter cloacae (n = 15), and Citrobacter freundii (n = 1). Checkerboard experiments were performed to study interactions over the range of 0.008 to 64 mg/liter
ceftolozane and 0.063 to 32 mg/liter
tazobactam using 2-fold-dilution series. The MIC50 and MIC90 of
ceftolozane alone for all isolates were 16 and ≥64 mg/liter, respectively. Increasing concentrations of
tazobactam resulted in decreasing MICs of
ceftolozane. The 50th and 90th percentile concentrations of
tazobactam required to reduce the MIC of
ceftolozane to 8 mg/liter for all organisms in this ESBL collection were 0.5 and 4 mg/liter, respectively. For E. coli, K. pneumoniae, and E. cloacae, these values were 0.5 and 2, 1 and 16, and 0.5 and 4 mg/liter, respectively. When combined with a fixed amount of 4 mg/liter
tazobactam (current CLSI concentration used for susceptibility testing), 90% of the isolates would have an MIC of ≤4 mg/liter. The combination
ceftolozane-tazobactam is a promising alternative option for treating
infections due to ESBL-harboring isolates.