Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling

Cornelia B. Landersdorfer, Rajbharan Yadav, Kate E. Rogers, Tae Hwan Kim, Beom Soo Shin, John D. Boyce, Roger L. Nation, Jürgen B. Bulitta

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB) isolate (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow-fiber infection model (inoculum, ∼107.2 CFU/ml) with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies achieved no killing or failed by 24 h, this rationally optimized combination achieved >5 log10 bacterial killing and suppressed resistance.

Original languageEnglish
Article numbere02053-17
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Acinetobacter baumannii
  • Carbapenem resistance
  • Dynamic hollow-fiber infection model
  • Mathematical modeling
  • Mechanism based
  • Mechanistic
  • Pharmacodynamics
  • Pharmacokinetics
  • Synergy

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