In vitro susceptibility of Paracoccidioides brasiliensis yeast form to antifungal agents

A study was conducted to determine the susceptibility of P. brasiliensis yeast form to amphotericin B (A), ketoconazole (K), 5-fluorocytosine (5-FC) and rifampin (R). The three isolates tested produced minimal inhibitory concentrations (MICs) (mcg/ml) in the following range: A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 and R: 40-80. The minimal fungicidal concentrations (MFC) were several times higher than the corresponding MICs. Precise MFC for 5-FC were not obtained (> 500 mcg/ml). Combination of K plus A proved synergic, with the fractional inhibitory concentration (FIC) indices revealing synergy when the drugs were combined at the 1 to 1 and 1 to 5 MIC ratios. R (40 mcg/ml) appeared to antagonize K. These results indicate promise for the combined use of K plus A as a therapeutical regimen.