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Prevention and Treatment of Yeast and Endemic Fungal Infections

ABSTRACT: Invasive fungal infections (IFIs) remain an important complication of solid organ transplantation owing to their significant morbidity and mortality and include infections due to Candida, Cryptococcus, endemic mycosis, and other rare yeasts and molds. IFIs occur in different intervals posttransplantation and depend on a number of extrinsic and intrinsic risk factors, some of which are specific to the type of organs transplanted, surgical techniques, and type of immunosuppressive medications. Donor-derived IFIs and emergence of new multidrug-resistant yeasts have been reported in various healthcare settings. Clinical manifestations of yeast and endemic fungal infections vary in different types of organ transplants. Diagnosis of IFIs in SOT recipients is challenging due to their nonspecific signs and symptoms owing to the impaired inflammatory responses as a result of immunosuppression and the lack of highly sensitive and specific diagnostic modalities. Early diagnosis is key to successful therapy, and physicians should have a high index of suspicion based on risk factors and epidemiology of these pathogens. Antifungal treatment strategies for yeast infections have been outlined in various society guidelines. Management of complications that arise before or during antifungal therapy is critical for optimizing clinical response.

SUBMITTER: Manuel O

PROVIDER: S-EPMC7138456 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug-drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring.

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Prevention and Treatment of Yeast and Endemic Fungal Infections

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