Expression of CTX-M-15 limits the efficacy of ceftolozane/tazobactam against Escherichia coli in a high-inoculum murine peritonitis model. (October 2020)

• Record Type: Journal Article
• Authors: Canovas, J.; Petitjean, G.; Chau, F.; Le Monnier, A.; Fantin, B.; Lefort, A.
• Is Part Of: Clinical microbiology and infection. Volume 26:Number 10(2020)
• Page Start: 1416.e5
• Page End: 1416.e9
• Publication Date: 2020-10
• Subjects: Ceftolozane/tazobactam -- Carbapenem alternatives -- Extended-spectrum β-lactamase -- Inoculum effect -- Mouse peritonitis model; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2020.06.032
• Languages: English
• ISSNs: 1198-743X

Abstract

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 bla CTX-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 bla CTX-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.