Open AccessCombating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem-plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection and Mathematical Modeling
Author(s) -
Cornelia B. Landersdorfer,
Rajbharan Yadav,
Kate E. Rogers,
Tae Hwan Kim,
Beom Soo Shin,
John D. Boyce,
Roger L. Nation,
Jürgen B. Bulitta
Publication year - 2018
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02053-17
Subject(s) - acinetobacter baumannii , imipenem , tobramycin , cephalosporin , regimen , microbiology and biotechnology , carbapenem , medicine , acinetobacter , antibacterial agent , antibiotics , biology , pseudomonas aeruginosa , antibiotic resistance , bacteria , gentamicin , genetics
We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistantAcinetobacter 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.
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