title: Unexpected in vivo activity of ceftazidime alone and in combination with avibactam against New Delhi metallo-β-lactamase-producing Enterobacteriaceae in a murine thigh infection model.
abstract: The emergence of the New Delhi metallo-β-lactamase (NDM) among Enterobacteriaceae has become a global concern because of its high levels of in vitro resistance to nearly all available antibiotics. However, recent in vivo studies demonstrated the efficacies of carbapenems against NDM-1-producing isolates despite high MICs. Herein, we report in vivo findings with ceftazidime and ceftazidime-avibactam against an isogenic pair (wild type and NDM-1) and four clinical NDM-producing isolates that demonstrate discordance between MICs measured in vitro and the in vivo activity of ceftazidime-avibactam against this resistant genotype.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Shawn H
authors.initials: SH
authors.lastname: MacVane
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Jared L
authors.initials: JL
authors.lastname: Crandon
authors.affiliation: AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.
authors.forename: Wright W
authors.initials: WW
authors.lastname: Nichols
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D015780:Carbapenems; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime; C533914:metallo-beta-lactamase (VIM-13), Pseudomonas aeruginosa; D001618:beta-Lactamases