micafungin and Fusariosis

Fusarium species cause a broad spectrum of infections, from superficial to disseminated disease. Because Fusarium species are intrinsically resistant to most antifungal drugs, new approaches are needed. The aim of the present study was to evaluate the in vitro combination of natamycin with currently used antifungal drugs.. The in vitro interactions of combinations between natamycin and voriconazole, itraconazole and micafungin applied to 20 clinical Fusarium strains (members of Fusarium falciforme, Fusarium napiforme, Fusarium petroliphilum, Fusarium proliferatum, Fusarium pseudensiforme and Fusarium sacchari) were evaluated using a chequerboard microdilution method. The MICs of all drugs alone and in combination were determined visually after 48 h and interactions were assessed using fractional inhibitory concentration index (FICI) analysis.. MICs of voriconazole and natamycin alone were 4 to >16 and 4-8 mg/L, respectively. Values were reduced 3.5-10-fold to 0.02-0.5 mg/L and 0.5-5-fold to 0.13-2 mg/L in combination, for the currently used antifungals and natamycin, respectively, demonstrating additive to synergistic interactions. The combinations natamycin/voriconazole, natamycin/itraconazole and natamycin/micafungin were synergistic (FICI ≤0.5) for 70%, 15% and 5% of the strains, respectively. No antagonism was found.. The combination of natamycin with voriconazole was strongly synergistic at clinically achievable serum concentrations.

Topics: Antifungal Agents; Dermatomycoses; Drug Combinations; Drug Interactions; Drug Synergism; Echinocandins; Fusariosis; Fusarium; Itraconazole; Keratitis; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Voriconazole

The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.

Topics: Adenine Nucleotides; Adult; Anidulafungin; Antibiotic Prophylaxis; Antifungal Agents; Antimetabolites, Antineoplastic; Arabinonucleosides; Candida; Candidiasis, Invasive; Caspofungin; China; Clofarabine; Cohort Studies; Cross Infection; Echinocandins; Fusariosis; Fusarium; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Lipopeptides; Lung Diseases, Fungal; Micafungin; Retrospective Studies; Risk Factors