Interactions of rifampin and trimethoprim in vitro.
Combination of rifampin and trimethoprim (TMP) has been suggested as a means of preventing the emergence of bacterial resistance to the individual agents and of achieving synergistic antimicrobial activity. By means of standard techniques of antimicrobial susceptibility testing, combinations of rifampin and TMP were tested against clinical isolates of a variety of aerobic bacteria. Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration (MIC) of the more active agent in the combination. Antagonism was defined as a fourfold or greater increase in the MIC of the more active agent. No change or, at most, a twofold change was considered to represent indifference. Combinations of rifampin and TMP in ratios of 7:1, 7:2, and 1:1 demonstrated synergistic activity against 12%, 13%, and 28% of 440 isolates, respectively. Antagonism was observed in 10%, 9%, and 8% of strains tested against the above ratios. Killing curves determined with selected organisms failed to demonstrate synergistic antibacterial activity. Combinations of rifampin and TMP failed to prevent the emergence of resistance to both drugs when selected strains of various bacteria were exposed to serial, subinhibitory concentrations. Thus, synergism of rifampin and TMP was observed in only a minority of strains tested, and combination of the two agents failed to prevent the emergence of drug resistance in vitro.
D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000382:microbiology; D004347:Drug Interactions; D004352:Drug Resistance, Microbial; D004755:Enterobacteriaceae / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D012293:Rifampin / Q000494:pharmacology*; D014295:Trimethoprim / Q000494:pharmacology*
D014295:Trimethoprim; D012293:Rifampin