title: In vitro inhibitory effect of antituberculosis drugs on clinical and environmental strains of Coccidioides posadasii.
abstract: OBJECTIVE
  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.
authors.affiliation: Medical Mycology Specialized Center, Federal University of Ceará Fortaleza, Ceará, Brazil. ross@uece.br
authors.forename: Rossana
authors.initials: R
authors.lastname: de Aguiar Cordeiro
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brilhante
authors.forename: Marcos Fábio Gadelha
authors.initials: MF
authors.lastname: Rocha
authors.forename: Maria Auxiliadora Bezerra
authors.initials: MA
authors.lastname: Fechine
authors.forename: Zoilo Pires de
authors.initials: ZP
authors.lastname: Camargo
authors.forename: José Júlio Costa
authors.initials: JJ
authors.lastname: Sidrim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D003045:Coccidioides / Q000187:drug effects* / Q000302:isolation & purification; D003047:Coccidioidomycosis / Q000382:microbiology*; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D000995:Antitubercular Agents