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Despite limited data, polymyxin B (PB) is increasingly used clinically as the last therapeutic option for multidrug-resistant (MDR) gram-negative bacterial infections. We examined the in vitro pharmacodynamics of PB against four strains of Pseudomonas aeruginosa. Clonal relatedness of the strains was assessed by random amplification of polymorphic DNA. Time-kill studies over 24 h were performed with approximately 10⁵ and 10⁷ CFU/ml of bacteria, using PB at 0, 0.25, 0.5, 1, 2, 4, 8, and 16× MIC. Dose fractionation studies were performed using an in vitro hollow-fiber infection model (HFIM) against a wild-type and a MDR strain. Approximately 10⁵ CFU/ml of bacteria were exposed to placebo and three regimens (every 8 h [q8h], q12h, and q24h) simulating the steady-state unbound PB pharmacokinetics resulting from a daily dose of 2.5 mg/kg of body weight and 20 mg/kg (8 times the clinical dose). Samples …