In vitro inhibitory effect of antituberculosis drugs on clinical and environmental strains of Coccidioides posadasii

OBJECTIVES: The aim of the present study was to evaluate the in vitro effect of the first-line antimicrobial drugs for pulmonary tuberculosis against the fungal pathogen Coccidioides posadasii. METHODS: The in vitro activities of rifampicin, isoniazid, pyrazinamide and ethambutol against clinical and environmental strains of C. posadasii were determined in accordance with the CSLI M38-A macrodilution method. The antimicrobials were tested alone or in combinations of two or more drugs. RESULTS: With the exception of pyrazinamide, all of the tested drugs interfered with the in vitro growth of C. posadasii. The 2 day MIC ranges of the tested drugs were as follows: rifampicin 1,060-4,250 mg/L; isoniazid < or =250 mg/L; ethambutol < or =620 mg/L. Pronounced in vitro synergism was demonstrated for combined antituberculosis drugs. The combination of rifampicin plus pyrazinamide was the only one that did not inhibit fungal growth. CONCLUSIONS: The present study showed that the first-line antituberculosis drugs, alone or in combinations, interfered with the vegetative growth of C. posadasii strains in vitro. Further studies in a murine model will need to be conducted in order to evaluate the in vivo effect of antituberculosis drugs on Coccidioides spp.