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, Lilian Abbo, R. Rosa, Jose Camargo Galvis, Octavio V. Martinez, R. A. Bonomo, D. P. Nicolau

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 - Jul 1 2017

Fingerprint

Aztreonam
Klebsiella pneumoniae
Lung
Infection
Bacteria
Enterobacteriaceae
Phenotype
ceftazidime drug combination avibactam
beta-lactamase NDM-1
tigecycline
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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title = "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",
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.",
keywords = "Ceftazidime-avibactam, Klebsiella pneumoniae, New Delhi metallo-β-lactamase, Resistance",
author = "Monogue, {M. L.} and Lilian Abbo and R. Rosa and {Camargo Galvis}, Jose and Martinez, {Octavio V.} and Bonomo, {R. A.} and Nicolau, {D. P.}",
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T2 - 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

AU - Monogue, M. L.

AU - Abbo, Lilian

AU - Rosa, R.

AU - Camargo Galvis, Jose

AU - Martinez, Octavio V.

AU - Bonomo, R. A.

AU - Nicolau, D. P.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Ceftazidime-avibactam

KW - Klebsiella pneumoniae

KW - New Delhi metallo-β-lactamase

KW - Resistance

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