Antifungal susceptibility of Aspergillus species isolated from invasive oral infection in neutropenic patients with hematologic malignancies

Objective. The aim of this study was to evaluate the relevance of in vitro antifungal susceptibility to clinical response in neutropenic patients with invasive oral aspergillosis. Study design. Nine isolates of Aspergillus species were obtained from invasive oral infections in 9 patients with hematologic malignancies and tested for their in vitro susceptibility to amphotericin B, fluconazole, miconazole, 5-fluorocytosine, and itraconazole. Minimal inhibitory concentration values of the 5 drugs were obtained for each fungus through use of a microdilution broth method. The patients were treated with intravenous amphotericin B (30-50 mg/day) in combination with oral 5-fluorocytosine (3000-6000 mg/day) and/or oral itraconazole (200 mg/day). Results. Amphotericin B and itraconazole were found to be very active, with minimal inhibitory concentration values of 0.861 and 0.194 mu g/mL, respectively. Miconazole and 5-fluorocytosine showed minimal inhibitory concentration values of 1.72 and 3.56 mu g/mL, respectively. On the other hand, fluconazole FCZ showed low activity, with a minimal inhibitory concentration value in excess of 64.0 mu g/mL. During neutropenia, combined antifungal chemotherapy stabilized oral aspergillosis and prevented the spread of oral lesions in 8 patients in whom neutrophil counts eventually recovered. Conclusions. The results imply that in vitro susceptibility testing may serve as an informative parameter with respect to the efficacy of these antifungals in the treatment of invasive oral aspergillosis, inducing fungal stasis until the neutrophils recover.