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: Shawn H MacVane, Jared L Crandon, Wright W Nichols, David P Nicolau
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 11 Pg. 7007-9 (Nov 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 25223998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Azabicyclo Compounds
• Carbapenems
• Drug Combinations
• avibactam, ceftazidime drug combination
• Ceftazidime
• metallo-beta-lactamase (VIM-13), Pseudomonas aeruginosa
• beta-Lactamases

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Azabicyclo Compounds (pharmacology)
• Carbapenems (pharmacology)
• Ceftazidime (pharmacology)
• Disease Models, Animal
• Drug Combinations
• Escherichia coli (drug effects, genetics, isolation & purification)
• Escherichia coli Infections (drug therapy, microbiology)
• Klebsiella Infections (drug therapy, microbiology)
• Klebsiella pneumoniae (drug effects, genetics, isolation & purification)
• Mice
• Microbial Sensitivity Tests
• beta-Lactamases (metabolism)