Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin.

In patients with hematologic malignancy, invasive aspergillosis continues to be associated with high mortality even when treated with conventional antifungal therapy. To investigate novel antifungal agents, we compared 53 patients who received posaconazole salvage therapy to 52 contemporary control patients who received high-dose lipid formulation of amphotericin B (HD-LPD/AMB at > or = 7.5 mg kg(-1) per day) and 38 other control patients who received caspofungin plus HD-LPD/AMB. Patients in the three groups had similar. The overall response rate to salvage therapy was 40% for posaconazole, 8% for HD-LPD/AMB (P < or = 0.001) and 11% for combination therapy (P < 0.002). Aspergillosis contributed to the death of 40% of posaconazole group, 65% of the HD-LPD/AMB group and 68% of the combination group (P < or = 0.008). By multivariate analysis, posaconazole therapy independently improved response (9.5; 95% confidence interval, 2.8-32.5; P < 0.001). HD-LPD/AMB alone or in combination was associated with a significantly higher rate of nephrotoxicity (P < or = 0.02) and hepatotoxicity (P < 0.03). In conclusion, posaconazole salvage therapy demonstrated greater efficacy and safety than HD-LPD/AMB alone or in combination with caspofungin in the salvage therapy of invasive aspergillosis in hematologic malignancy.

High-dose fluconazole therapy for cancer patients with solid tumors and candidemia: an observational, noncomparative retrospective study.

BACKGROUND: Response rates for candidemia treated with standard-dose fluconazole (400 mg/day) are approximately 70%. Higher doses of fluconazole have been recommended for susceptible dose-dependent Candida isolates. Herein, we describe the outcome of 20 patients with solid tumors and candidemia treated with high-dose fluconazole (HDF) at The University of Texas M.D. Anderson Cancer Center (1998-2002). PATIENTS AND METHODS: Patients were identified either by searching the microbiology laboratory database or through direct referral from primary oncology services to the Infectious Diseases Consultative Services. A retrospective review of cases was performed. HDF was defined as > or =600 mg/day. RESULTS: Five patients were treated with 600 mg/day, whereas 15 patients received 800 mg/day. Only one patient was neutropenic. The median APACHE II score at the onset of candidemia was 12 (range 6-24). The most common species identified were Candida albicans (eight patients, 40%) and Candida parapsilosis (seven patients, 35%). Of 19 patients whose quantitative data were available, eight (42%) had high-grade candidemia [> or =200 colony forming units (CFU)/ml]. Fifteen (83%) of 18 isolates were fluconazole susceptible, and two (both Candida glabrata) were fluconazole resistant (MIC 64 each) in vitro. Nineteen patients (95%) responded to HDF therapy. The only HDF failure occurred in a patient with C. glabrata (MIC 64.0) infection. The other patient with C. glabrata (MIC 64.0) infection responded to HDF. Central venous catheters were removed from all patients with > or =10 CFU/ml candidemias. All patients with high-grade candidemias responded to HDF. The median duration of HDF therapy was 16 (range 6-42) days. No significant toxicity occurred. CONCLUSIONS: Although our data are limited, HDF appears to be well tolerated and may be associated with higher response rates than standard-dose fluconazole in a selected group of patients with solid tumors and candidemia caused by species that are susceptible to this triazole.