Expression of CTX-M-15 limits the efficacy of ceftolozane/tazobactam against Escherichia coli in a high inoculum murine peritonitis model.

Abstract Objectives Among carbapenem-sparing therapies, ceftolozane/tazobactam has been proposed for the treatment of infections due to CTX-M-15 producing Escherichia coli. However, few data exist on its in vivo activity in infections associated with a high bacterial inoculum. Methods We analyzed ceftolozane/tazobactam activity against susceptible E. coli CFT073-RR and its CTX-M-15-producing transconjugant E. coli CFT073-RR Tc blaCTX-M-15, in vitro at low and high inoculum, and in a high-inoculum murine model of peritonitis. Results Against E. coli CFT073-RR Tc blaCTX-M-15, ceftolozane/tazobactam bactericidal effect was impaired in vitro with only a minor inoculum effect; this translated into a reduced activity as compared with imipenem in the mouse peritonitis model. Conclusions Combination of ESBL expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.