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

: 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.