Abstract
BACKGROUND: Isavuconazole (ISA) is a newer triazole that has activity against most mold species and has been utilized for prophylaxis as well as treatment in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HSCT). However, several studies have documented breakthrough invasive fungal infections (bIFIs). Thus, we conducted a systematic review and meta-analysis to investigate the incidence of bIFIs among patients receiving ISA prophylaxis. METHODS: We conducted a systematic review and meta-analysis of the published literature using the concept of ISA, HSCT, and HM from 5 search engines. In patients with HSCT and HM, the pooled incidence of bIFI while undergoing ISA prophylaxis was calculated via the DerSimonian-Laird random effect model. RESULTS: The systematic review and meta-analysis included 35 and 19 studies, respectively. In total, 991 patients were identified as using ISA prophylaxis, and the majority had either acute myeloid leukemia or myelodysplastic syndrome (69.9%). The pooled incidence of proven/probable bIFI was 7% (95% CI, 4%-12%, I(2) = 55%). The most common pathogen was Aspergillus species (43.1%), followed by Candida (22.4%) and Mucorales (12.1%). In 19 studies, mortality rates were documented and ranged between 0% and 100%; the majority of which were >50%. CONCLUSIONS: In patients with HM or HSCT, we found a high incidence of bIFI while undergoing ISA prophylaxis, with high mortality. Given the lack of randomized clinical trials evaluating ISA in this indication, its role in prophylaxis remains unclear.