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 ≤0.4 μg/ml) when an inoculum of 10⁴ colony-forming units (CFU) was used, 10 of the 14 strains manifested resistance to this agent when an inoculum of 10⁸ CFU was tested. The mutation rate for rifampin resistance ranged from 1 resistant colony per 3.5 x 10⁶ CFU to 1 per 4 x 10⁷ 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.