In vitro discordance with in vivo activity: Humanized exposures of ceftazidime-avibactam, aztreonam, and tigecycline alone and in combination against New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae in a murine lung infection model

M. L. Monogue, L. M. Abbo, R. Rosa, J. F. Camargo, O. Martinez, R. A. Bonomo, D. P. Nicolau

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The management of infections with New Delhi metallo-beta-lactamase-1 (NDM)-producing bacteria remains clinically challenging given the multidrug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM-positive Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against an MDR Klebsiella pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in >2 log10 CFU bacterial reduction; therefore, no in vivo synergy was observed.

Original languageEnglish (US)
Article numbere00486
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number7
DOIs
StatePublished - Jun 2017
Externally publishedYes

Keywords

  • Ceftazidime-avibactam
  • Klebsiella pneumoniae
  • New Delhi metallo-β-lactamase
  • Resistance

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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