Background: Hospital infections caused by Acinetobacter baumannii tend to be resistant to various antibiotics.Colistin is increasingly used worldwide as the last-line therapy against A.baumannii.The renal toxicity and resistance emergence during monotherapy is concerning.Here, our objective is to reduce the dose level of colistin through combination strategy with meropenem by profiling the time course of synergistic killing and prevention the emergence of colistin resistance in treating A.baumannii infections.Methods: In vitro flow rate modulation models over 10 hours simulated clinically relevant dosage regimens of colistin and meropenem against standard A.baumannii strains (ATCC19606) and one carbapenem resistant (MICCOL 1 mg/L, MICMER 128 mg/L) strain isolated from clinics.A mechanism-based pharmacokinetic-pharmacodyamic model was developed using NONMEM.Results: Against standard A.baumannii strains strains, meropenem 500mg single dose monotherapy resulted in 2.05 log10 cfu/mL initial killing within 5 h followed by regrowth,and 0.25 mg/L colistin achieved 1.51 log10 cfu/mL killing followed by slow regrowth in 1 h after dose.High-intensity combinations involving free steady-state colistin concentrations of 0.25 mg/L achieved 5.34 log10 killing within 4.5 h.These combinations achieved synergy with up to 3.83 log10 greater killing compared with colistin monotherapy.The model quantified total and resistant subpopulations and the proposed synergy between colistin and meropenem.Based on simulation, 800 mg qd meropenem and 0.25 mg/L colistin can achieve 6.5 log10 killing within 24 h without regrowth.Conclusions: Applying 0.25 mg/L colistin and 800mg qd meropenem may achieve complete eradication and good safety.This finding should be investigated in in-vitro experiments and clinical trials