Susceptibility of strains of the Mycobacterium tuberculosis complex to fusidic acid.

Abstract

The activity of fusidic acid was studied in 40 strains of M. tuberculosis (of which 20 strains were mono- or multiresistant to standard antituberculosis drugs) and 10 strains of M. bovis. Minimum inhibitory concentration (MIC) was determined by the radiometric (BACTEC) broth method. The MIC for the 50 strains varied between 8 and 32 mg/l, with a MIC90 of 16 mg/l for M. tuberculosis and a MIC90 of 32 mg/l for M. bovis. Minimal bactericidal concentration (MBC, defined as the lowest concentration of fusidic acid which killed 99% or more of the population) varied between 32 mg/l and 500 mg/l, with a MBC90 of 250 mg/l for M. tuberculosis and 500 mg/l for M. bovis. No cross-resistance to other antituberculosis drugs (ethambutol, isoniazid, rifampicin, streptomycin, pyrazinamide, ofloxacin, ciprofloxacin) was observed as strains resistant to one or more standard antituberculosis drugs were as susceptible to fusidin as sensitive strains of M. tuberculosis. No synergism or antagonism could be demonstrated when fusidic acid was combined with either ethambutol, isoniazid, rifampicin or streptomycin against strains of M. tuberculosis resistant to one or more standard antituberculosis drugs. Addition of pooled human serum to the medium increased both MIC and MBC by factors of 4 and 8 at serum concentrations of 10% and 50%, respectively. Single-step mutation to high-level resistance to fusidic acid at a frequency of less than 1.7 x 10(-8) could be readily selected at four times the MIC. These fusidic acid-resistant organisms had a generation time 2.0-2.7 x longer than their parent organisms.