J Canovas1, G Petitjean2, F Chau1, A Le Monnier2, B Fantin3, A Lefort4. 1. IAME, UMR 1137, INSERM, F-75018, Université de Paris, Paris, France. 2. Department of Microbiology, Hôpital Saint-Joseph, Paris, France. 3. IAME, UMR 1137, INSERM, F-75018, Université de Paris, Paris, France; Internal Medicine Department, Hôpital Beaujon, AP-HP, Clichy, France. 4. IAME, UMR 1137, INSERM, F-75018, Université de Paris, Paris, France; Internal Medicine Department, Hôpital Beaujon, AP-HP, Clichy, France. Electronic address: agnes.lefort@aphp.fr.
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 analysed 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 inocula, 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 reduced activity compared with imipenem in the mouse peritonitis model. CONCLUSIONS: Combination of extended spectrum β-lactamase expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.
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 analysed 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 inocula, 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 reduced activity compared with imipenem in the mouse peritonitis model. CONCLUSIONS: Combination of extended spectrum β-lactamase expression and high inoculum size may be a clinical situation at risk of reduced bactericidal activity of ceftolozane/tazobactam.