In vitro susceptibility studies of Cryptococcus neoformans isolated from patients with no clinical response to amphotericin B therapy

The in vitro activities of three antifungal drugs alone and in combination were evaluated against five isolates of Cryptococcus neoformans using time- kill curves (TKC). The isolates were from AIDS patients who had either died or had failed to show a clinical response during amphotericin B (AMB) trea tment. AMB, fluconazole (FCZ) and flucytosine (5FC), and combinations of th e drugs (AMB plus 5FC, AMB plus rifampicin (RIF) and FCZ plus 5FC), were ev aluated. With all five isolates AMB did not show fungicidal activity; inste ad, a persistent or tolerant effect was observed. Combinations of AMB plus 5FC and AMB plus RIF showed a clear synergic effect, except for one isolate tested with AMB plus RIF. In contrast, the FCZ plus 5FC combination did no t inhibit growth of any isolate.