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Isavuconazole is the newest of the clinically available advanced generation triazole antifungals and is active against a variety of yeasts, molds, and dimorphic fungi. Its current FDA-approved indications include the management of invasive aspergillosis as well as mucormycosis, though the latter indication is supported by limited clinical data. Isavuconazole did not achieve noninferiority to caspofungin for the treatment of invasive candidiasis and therefore lacks an FDA-approved indication for this invasive disease. Significant advantages of isavuconazole, primarily over voriconazole but in some circumstances posaconazole as well, make it an appealing option for the management of complex patients with invasive fungal infections. These potential advantages include lack of QTc interval prolongation, more predictable pharmacokinetics, a less complicated drug interaction profile, and improved tolerability, particularly when compared to voriconazole. This review discusses these topics in addition to addressing the in vitro activity of the compound against a variety of fungi and provides insight into other distinguishing factors among isavuconazole, voriconazole, and posaconazole. The review concludes with an opinion section in which the authors provide the reader with a framework for the current role of isavuconazole in the antifungal armamentarium and where further data are required.

Background Isavuconazole (ISA) is an attractive candidate for primary mold-active prophylaxis in high-risk patients with hematologic malignancies or hematopoietic cell transplant (HCT) recipients. However, data supporting the use of ISA for primary prophylaxis in these patients are lacking. Methods We conducted a retrospective review of breakthrough invasive fungal infections (bIFIs) among adult hematologic malignancy patients and HCT recipients who received ≥7 days of ISA primary prophylaxis between 1 September 2016 and 30 September 2018. The incidence of bIFIs in patients receiving ISA was compared to those receiving posaconazole (POS) and voriconazole (VOR) during the same time period. Results One hundred forty-five patients received 197 courses of ISA prophylaxis. Twelve bIFIs (Aspergillus fumigatus [5], Aspergillus species [2], Mucorales [2], Fusarium species [2], and Candida glabrata [1]) occurred, representing 8.3% of patients and 6.1% of courses, after a median duration of 14 days of ISA prophylaxis. All bIFIs occurred during periods of neutropenia. Seven patients (58.3%) died within 42 days of onset of bIFI. In addition, bIFIs complicated 10.2% of ISA, 4.1% of POS, and 1.1% of VOR courses among patients with de novo or relapsed/refractory acute myeloid leukemia during the study period, with invasive pulmonary aspergillosis (IPA) complicating 6.8% of ISA, 1.3% of POS, and zero VOR courses. Conclusions Although ISA has been approved for treatment of invasive Aspergillus and mucormycosis, we observed an increased rate of bIFI, notably IPA, using ISA for primary prophylaxis. These results support the need for further study to determine the role of ISA as primary prophylaxis. [ABSTRACT FROM AUTHOR]

The risk of toxoplasmosis in high‐risk cardiac transplant recipients is well recognized prompting universal donor and candidate screening with administration of targeted post‐transplant chemoprophylaxis in high‐risk (D+/R−) cardiac transplant patients. In contrast, until recently, there have been neither well‐defined recommendations nor consensus regarding toxoplasmosis preventive strategies among non‐cardiac solid organ transplant recipients. We report 3 cases of post‐transplant toxoplasmosis in non‐cardiac transplant recipients (one lung and two liver); all 3 infections presumed to be donor‐derived. Not surprisingly, pre‐transplant Toxoplasma serology was negative in all the patients. None of the patients were on trimethoprim‐sulfamethoxazole (TMP‐SMX) prophylaxis at the time of diagnosis of toxoplasmosis. The median time from transplant to onset of infection was 90 days (range: 30‐120 days). Clinical presentations included cerebral (n = 1) and disseminated infections (n = 2). Two of the 3 patients, both with disseminated infection died (mortality ~ 67%). [ABSTRACT FROM AUTHOR]