title: Activity of fosfomycin alone or combined with cefoxitin in vitro and in vivo in a murine model of urinary tract infection due to Escherichia coli harbouring CTX-M-15-type extended-spectrum β-lactamase.
abstract: The efficacy of fosfomycin alone or combined with cefoxitin was investigated in vitro and in a murine model of urinary tract infection due to susceptible Escherichia coli CFT073-RR and its transconjugant CFT073-RR Tc (pblaCTX-M-15) harbouring a plasmid carrying the blaCTX-M-15 gene. In vitro, the combination of cefoxitin and fosfomycin was synergistic and bactericidal and prevented the emergence of fosfomycin-resistant mutants of CFT073-RR and CFT073-RR Tc (pblaCTX-M-15) that were selected with fosfomycin alone. In vivo, the combination conferred an advantage in terms of kidney sterilisation of mice infected with either strain compared with fosfomycin monotherapy.
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France. Electronic address: agnes.lefort@bjn.aphp.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Lefort
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Chau
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Lepeule
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dubée
authors.affiliation: Service de Microbiologie, Hôpital Saint-Joseph, Paris, France.
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Kitzis
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Dion
authors.affiliation: EA3964, Faculté de Médecine Xavier Bichat, Université Paris-Diderot, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fantin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002440:Cefoxitin / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy; D005260:Female; D005578:Fosfomycin / Q000627:therapeutic use*; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests; D014552:Urinary Tract Infections / Q000188:drug therapy*; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D002440:Cefoxitin; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases
keywords: Cefoxitin; Escherichia coli; Extended-spectrum β-lactamase; Fosfomycin