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

Islam M Ghazi; Jared L Crandon; Emil P Lesho; Patrick McGann; David P Nicolau

doi:10.1128/AAC.00794-15

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

Antimicrob Agents Chemother. 2015 Nov;59(11):7145-7. doi: 10.1128/AAC.00794-15. Epub 2015 Sep 28.

Authors

Islam M Ghazi¹, Jared L Crandon¹, Emil P Lesho², Patrick McGann², David P Nicolau³

Affiliations

¹ Center for Anti-infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
² Multidrug-resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
³ Center for Anti-infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Infective Agents / pharmacology*
Anti-Infective Agents / therapeutic use*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Cefepime
Cephalosporins / pharmacology
Cephalosporins / therapeutic use
Enterobacteriaceae / drug effects*
Enterobacteriaceae / enzymology*
Enterobacteriaceae Infections / drug therapy
Levofloxacin / pharmacology
Levofloxacin / therapeutic use
Meropenem
Mice
Microbial Sensitivity Tests
Thienamycins / pharmacology
Thienamycins / therapeutic use
Thigh / microbiology*
beta-Lactamases / genetics
beta-Lactamases / metabolism*

Substances

Anti-Infective Agents
Bacterial Proteins
Cephalosporins
Thienamycins
Levofloxacin
Cefepime
beta-Lactamases
carbapenemase
Meropenem