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.