Activity of colistin against heteroresistant Acinetobacter baumannii and emergence of resistance in an in vitro pharmacokinetic/pharmacodynamic model

Three clinically relevant intermittent regimens, and a continuous infusion, of colistin were simulated in an in vitro pharmacokinetic/pharmacodynamic model against two colistin-heteroresistant strains of Acinetobacter baumannii. Extensive initial killing was followed by regrowth as early as 6 h later; bacterial density in the 24- to 72-h period was within 1 log(10) CFU/ml of growth control. Population analysis profiles revealed extensive emergence of resistant subpopulations regardless of the colistin regimen.