In Vitro Activity of Colistin and Trimethoprim/Sulfamethoxazole Against Consortia of Multidrug Resistant Non-Fermenting Gram-Negative Bacilli Isolated from Lower Respiratory Tract

Background: Multidrug resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia have a leading role in nosocomial infections, including lower respiratory tract (LRT) infections. When polymicrobial infection by these three bacteria occurs, colistin against MDR P. aeruginosa and A. baumannii and trimethoprim/sulfamethoxazole (SXT) against S. maltophilia can be an optional antimicrobial strategy. Objectives: The aim of this study was to investigate the potential synergic effect of colistin-plus-SXT against those MDR P. aeruginosa, A. baumannii and S. maltophilia isolates that were isolated at the same time, from the same LRT sample of patients. Methods: Sixty connected isolates from 20 different patients were collected in a two-year study period. The checkerboard method and time-kill assays were used for synergy testing. Results: All P. aeruginosa and A. baumannii strains were susceptible to colistin, whereas all S. maltophilia isolates were resistant to it. Fifteen percent of MDR A. baumannii strains and all S. maltophilia isolates were susceptible to SXT. By the checkerboard method, colistin-plus-SXT showed synergy in 50%, 35% and 45% of S. maltophilia, MDR P. aeruginosa and MDR A. baumannii strains, respectively. Antagonistic effect was not found. A time-kill assay was performed on strains which showed synergy by the checkerboard method: 70%, 57% and 56% of S. maltophilia, P. aeruginosa and A. baumannii strains showed the same results. Synergic activity of the combination was already detected after 6 h incubation in 86% of S. maltophilia isolates and 50% of P. aeruginosa strains. Regrowth of A. baumannii after 24 hour in the presence of colistin was prevented by the combination. The results gained by CB and TKA methods correlated in 61% of cases, but the ΣFIC values did not correlate with the rate of log10 decrease in TKA. Colistin-plus-SXT combination had synergic effect on 35% of S. maltophilia, 20% of P. aeruginosa and 25% A. baumannii strains by both methods. Conclusions: According to our in vitro results, colistin-plus-SXT combined therapy can be used efficiently in clinical practice as no antagonistic effect was detected. In certain cases colistin-plus-SXT has a synergic effect against MDR P. aeruginosa, A. baumannii and S. maltophilia.