In vitro pharmacodynamic properties of colistin methanesulfonate and amikacin against Pseudomonas aeruginosa

Purpose: In vitro pharmacodynamic properties of colistin methanesulfonate and amikacin were investigated by studying time-kill kinetics and post-antibiotic effect (PAE) against strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Method: Synergy was investigated at 0.5x, 1x and 5x MIC of antibiotics using time-kill curve method. PAEs were determined by the standard viable counting method where bacteria in the logarithmic phase of growth were exposed for 1 h to the antibiotics at 1x or 20x MIC, alone and in combinations. Synergy and additive effects were detected at 1xMIC, at 24 h. Results: Some of the strains produced an earlier synergistic effect at 12 h. No antagonism was observed. Colistin methanesulfonate and amikacin produced PAEs 1.16 +/- 0.10 to 2.25 +/- 0.16 h and 0.96 +/- 0.15 to 2.69+/-0.32 h, respectively. When the antibiotics were used in combination the PAEs were prolonged to a value of 3.88+/-0.25 h. Consequently, the Conclusions: Findings of this study may play useful role in selecting the appropriate combinations when a single agent is inadequate, and may have important information for optimizing the dose intervals