title: Efficacy of humanized high-dose meropenem, cefepime, and levofloxacin against Enterobacteriaceae isolates producing Verona integron-encoded metallo-β-lactamase (VIM) in a murine thigh infection model.
abstract: We aimed to describe the in vivo activity of humanized pharmacokinetic exposures of meropenem and comparators against Verona integron-encoded metallo-β-lactamase (MBL) (VIM)-producing Enterobacteriaceae in a murine model. Levofloxacin activity was predicted by its MIC, and cefepime activity displayed variability, whereas meropenem produced a >1 log CFU reduction against all isolates despite high MICs indicative of resistance. Our results suggest that despite in vitro resistance, high-dose meropenem may be a possible option against infections caused by Enterobacteriaceae producing MBL-type carbapenemases.
authors.affiliation: Center for Anti-infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Islam M
authors.identifier: http://orcid.org/0000-0003-1108-7706
authors.initials: IM
authors.lastname: Ghazi
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: Multidrug-resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Emil P
authors.initials: EP
authors.lastname: Lesho
authors.affiliation: Multidrug-resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: McGann
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; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D064704:Levofloxacin / Q000494:pharmacology / Q000627:therapeutic use; D000077731:Meropenem; D051379:Mice; D008826:Microbial Sensitivity Tests; D013845:Thienamycins / Q000494:pharmacology / Q000627:therapeutic use; D013848:Thigh / Q000382:microbiology*; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D013845:Thienamycins; D064704:Levofloxacin; D000077723:Cefepime; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem