Micafungin breakthrough fungemia in patients with hematological disorders [PublishAheadOfPrint]

Limited data are available on micafungin breakthrough fungemia (MBF), fungemia that develops on administration of micafungin, in patients with hematological disorders. We reviewed medical and microbiological records of patients with hematological disorders who developed MBF between January 2008 and June 2015. A total of 39 patients with MBF were identified and Candida (30 strains) and non-Candida (9 strains) fungal species were recognized as causative strains. Among 35 stored strains, C. parapsilosis (14 strains), Trichosporon asahii (7 strains), C. glabrata (5 strains), and other fungal species (9 strains) were identified by sequencing. Neutropenia was identified as an independent predictor of non-Candida fungemia (P = 0.023). T. asahii was the most common causative strain (7/19) during neutropenia. The 14-day crude mortality rate of patients treated with early micafungin change (EMC) to other antifungal agents was lower than that of the patients not treated with EMC (14% vs. 43%, P = 0.044). Most of the stored causative Candida strains were susceptible (80%) or showed wild-type susceptibility (72%) to micafungin. The minimum inhibitory concentrations (MICs) of voriconazole for T. asahii were low (range, 0.015 to 0.12 μg/mL), whereas MICs of amphotericin B for T. asahii were high (range, 2 to 4 μg/mL). MBF caused by non-Candida fungus should be considered, especially in patients with neutropenia. EMC could improve early mortality. Based on epidemiology and drug susceptibility profiling, empiric voriconazole-containing therapy might be suitable for treating MBF during neutropenia to cover for T. asahii.

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