Mutation frequency of Haemophilus influenzae to rifampin resistance

Abstract

Twenty-two susceptible strains of Haemophilus influenzae were examined for mutation to rifampin resistance (minimal inhibitory concentration, :10 ,ug/ml). All strains had detectable apparent mutation frequencies with a median minimal inhibitory concentration 2,000-fold greater than that of their wild-type parents. Of the type b strain mutants, 80%o (8 of 10) expressed high-level resistance (minimal inhibitory concentration, 750 ,ug/ml) that was 75-fold greater than readily achievable serum concentrations.Rifampin administration has been advocated to eliminate nasopharyngeal carriage of Haemophilus influenzae type b and to prevent secondary cases in susceptible contacts (4). A hazard of chemoprophylaxis is the emergence of resistant organisms, as has been shown for meningococci (3). Two reports have documented the emergence of rifampin-resistant (Rifr) H. influenzae in children who received rifampin prophylactically (8, 9). We had noted a significant number of Rifr mutants in conjugation experiments, which prompted us to examine 22 Rif' strains, selected on the bases of capsulation status, biotype, and concomitant antibiotic resistance, for their apparent frequency of spontaneous mutation to this resistant phenotype. Rifr mutants were tested for their susceptibility to the drug and examined for the stability of the resistance.

Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum

“…The mutation rates of the natural hypermutable isolates were variable and ranged from about 5-to 380-fold greater than Rd KW20 (R652). These mutation frequency values are consistent with a previous report describing H. influenzae mutation frequencies to rifampicin resistance ranging from 10 29 to 10 26 (Mendelman et al, 1982). Some isolates produced higher mutation frequencies to one antibiotic compared to the others.…”

Trimethoprim and rifampin in combination for chemoprophylaxis of household contacts of patients with invasive infections due to Haemophilus influenzae type b

“…Mutation to rifampin resistance occurs readily in vitro (8,12). Moreover, failure of rifampin prophylaxis has been associated with isolation of resistant strains of H. influenzae (10,11).…”