Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of Pseudomonas

Abstract

Eleven strains of tobramycin-susceptible Pseudomonas aeruginosa, 12 strains of tobramycin-resistant P. aeruginosa, and 11 strains of P. maltophilia were tested against tobramycin in combination with azlocillin, piperacillin, ceftazidime, and imipenem and against colistin in combination with azlocillin, piperacillin, ceftazidime, and imipenem by microdilution checkerboard and time-kill curve techniques. Synergistic or additive effects were demonstrated in the tobramycin-ceftazidime combination against tobramycin-resistant strains of P. aeruginosa and P. maltophilia, and with all tobramycin combinations against tobramycin-susceptible strains of P. aeruginosa using the checkerboard technique. Synergistic and additive effects were seen with the time-kill curve technique with colistin-ceftazidime, colistin-imipenem, and tobramycin-piperacillin combinations against tobramycin-susceptible P. aeruginosa and in the colistin-ceftazidime combination against tobramycin-resistant P. aeruginosa. Fractional inhibitory concentrations (FIC) and fractional bactericidal concentrations (FBC) from checkerboard studies were compared to the time-kill curve results and vice versa. The overall agreement with FIC was 39.4% and 40.9% and agreement with FBC was 40.9% and 43.9%. This limited study illustrates the lack of agreement between these techniques in demonstrating antimicrobial synergy against pseudomonads.