Differences in suppression of regrowth and resistance despite similar initial bacterial killing for meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli

Phillip J. Bergen, Jürgen B. Bulitta, Fekade B. Sime, Jeffrey Lipman, Megan J. McGregor, Nada Millen, David L. Paterson, Carl M.J. Kirkpatrick, Jason A. Roberts, Cornelia B. Landersdorfer

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3 Citations (Scopus)

Abstract

We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2–8×MIC for P. aeruginosa and 2–64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8–16×MIC for P. aeruginosa and 4–16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalDiagnostic Microbiology and Infectious Disease
Volume91
Issue number1
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • Bacterial killing
  • beta-Lactam antibiotics
  • In vitro studies
  • Resistance

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