In vitro development of rifampin resistance in clinical isolates of Haemophilus influenzae type b.

Although all of 14 clinical isolates of Haemophilus influenzae type b strains demonstrated rifampin susceptibility in vitro (minimal inhibitory concentration less than or equal to 0.4 microgram/ml) when an inoculum of 10(4) colony-forming units (CFU) was used, 10 of the 14 strains manifested resistance to this agent when an inoculum of 10(8) CFU was tested. The mutation rate for rifampin resistance ranged from 1 resistant colony per 3.5 x 10(6) CFU to 1 per 4 x 10(7) CFU. The emergence of rifampin-resistant mutants was prevented when trimethoprim was combined with rifampin. This finding suggests that when used alone for prophylaxis of H. influenzae type b nasopharyngeal carriers, rifampin is likely to lead to the emergence of resistant strains.