title: Synergy of colistin with rifampin and trimethoprim/sulfamethoxazole on multidrug-resistant Stenotrophomonas maltophilia.
abstract: Stenotrophomonas maltophilia is characterized by intrinsic resistance to a variety of antimicrobials. Therapeutic options are often limited particularly after the emergence of isolates resistant to trimethoprim/sulfamethoxazole. The application of colistin for infections caused by multidrug-resistant Gram-negative pathogens is limited due to its toxicity. In order to evaluate the activity of the interaction of colistin with rifampin or trimethoprim/sulfamethoxazole on S. maltophilia, 24 different isolates resistant to trimethoprim/sulfamethoxazole were in vitro exposed over-time to the combination of 1x and 4 x MIC of colistin with 2 microg/ml of rifampin or 2/38 microg/ml of trimethoprim/sulfamethoxazole. The applied concentrations for rifampin and trimethoprim/sulfamethoxazole reflect their mean serum levels. Synergy of colistin and rifampin was documented after the first two hours of bacterial growth for approximately 60% of isolates and it occurred with both applied concentrations of colistin. The interaction of colistin and rifampin prevented regrowth observed when single colistin was applied. Synergy of colistin and trimethoprim/sulfamethoxazole was mainly found when colistin was applied at a concentration of 4 x MIC involving 41.7% of isolates after 24 h of growth. In the presence of trimethoprim/sulfamethoxazole bacterial regrowth, observed when single colistin was applied, was prevented. It is concluded that growth of multidrug-resistant S. maltophilia is significantly inhibited by the interaction of colistin and rifampin and to a lesser extent of colistin and trimethoprim/sulfamethoxazole. These results merit further study in both the animal model and the clinical setting.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. giamarel@internet.gr
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Lazaros
authors.initials: L
authors.lastname: Karnesis
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003428:Cross Infection / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000494:pharmacology*; D020615:Stenotrophomonas maltophilia / Q000187:drug effects* / Q000254:growth & development; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D012293:Rifampin; D003091:Colistin