Marisela Tan

Abstract: To the Editor—Invasive fungal infections (IFIs) cause significant morbidity and mortality among immunocompromised hosts (IHs), particularly in those with hematologic malignancy and following stem-cell and solid organ transplantation. Prophylaxis with mold-active antifungals such as voriconazole and posaconazole is widely employed in high-risk populations to decrease IFIs and improve patient outcomes [1, 2]. Breakthrough IFIs due to resistant and atypical fungal pathogens are now increasingly described, however [3]. Isavuconazole is a broad-spectrum triazole antifungal approved by the Food and Drug Administration in 2015 [4] for treatment of invasive aspergillosis and mucormycosis [5, 6]. Although trials (NCT03019939) evaluating isavuconazole as antifungal prophylaxis in IHs are ongoing, it has already been implemented in many clinical settings [1] due to its broad spectrum of activity, ease of dosing, limited need for drug level monitoring, and favorable side effect and drug-drug interaction profile [4]. Little is known about the risk of breakthrough IFI with isavuconazole, particularly in the real-world setting. In a phase I trial of intravenous isavuconazole prophylaxis in acute myeloid leukemia patients, 18% (2/11) of patients in the low-dose arm (200 mg daily after loading) had treatment discontinued due to possible fungal infection [7]. In their 2016 abstract, Dadwal et al evaluated breakthrough IFIs among 131 patients at a single center with hematologic malignancy receiving more than 7 days of isavuconazole for empirical or directed treatment. Six (4.6%) patients developed breakthrough IFI, including 4 cases of proven/probable Aspergillus (unspecified species), 1 case of Rhizopus, and 1 case of Candida novegensis [8]. Another 2017 abstract retrospectively reviewed hematologic malignancy patients (N = 39) at MD Anderson Cancer Center receiving more than 7 days of isavuconazole prophylaxis or treatment, with 10% of patients developing proven/probable breakthrough IFI [9]. Among the 4 microbiologically-confirmed pathogens, 2 were mucormycosis, 1 was Candida parapsilosis, and 1 was Candida guillermondii. At our institution, we have been selectively using isavuconazole as primary or secondary prophylaxis in patients where voriconazole or posaconazole were contraindicated due to intolerance, need to avoid drug-drug interactions such as QT prolongation, or prior infection with resistant pathogens. Here we outline 5 cases of microbiologically confirmed C O R R E S P O N D E N C E