Invasive Fungal Infections in the Neutropenic Cancer Patient: Current Approaches and Future Strategies

Andreas H. Groll, MD, Thomas J. Walsh, MD

Disclosures

Infect Med. 2002;19(7) 

In This Article

Abstract and Introduction

Invasive fungal infections are important causes of morbidity and mortality in cancer patients with prolonged neutropenia following dose-intensive chemotherapy or hematopoietic stem cell transplantation. Recent epidemiologic trends indicate a shift toward infections by Aspergillus species, non-albicans Candida species, and previously uncommon fungal pathogens that have decreased susceptibility to current antifungal agents. In the last decade, much progress has been made in establishing disease definitions and paradigms for antifungal intervention and in the design and conduct of interventional clinical trials. This article reviews current approaches to prevention and treatment of opportunistic fungal infections in neutropenic patients and discusses novel approaches to antifungal chemotherapy and supportive measures.

Invasive fungal infections are important causes of morbidity and mortality in patients with hematologic malignancies and those who are undergoing hematopoietic stem cell transplantation (HSCT). The most significant risk factors in these settings are prolonged and profound neutropenia and therapy with high doses of corticosteroids. The overall frequency of invasive fungal infections in patients with acute leukemia and following allogeneic HSCT (the patient populations at highest risk) is between 10% and 25%; the overall case fatality rate exceeds 50% and is close to 100% in disseminated infections or persistent neutropenia. While Aspergillus and Candida species traditionally account for the majority of documented infections, recent epidemiologic trends indicate a shift toward infections by Aspergillus species, non-albicans Candida species, and previously uncommon fungi that often have little susceptibility to current antifungal agents.[1,2,3,4]

For many years, the antifungal arsenal consisted of amphotericin B desoxycholate (D-AmB) and 5-fluorocytosine (5-FC). Therapeutic alternatives only emerged with the clinical development of fluconazole and itraconazole in the late 1980s. In the past 10 years, however, we have witnessed a significant expansion in antifungal drug research, which is reflected by the introduction of the lipid formulations of amphotericin B (amphotericin B colloidal dispersion, amphotericin B lipid complex, and liposomal amphotericin B [L-AmB]) and the development of novel echinocandin derivatives (anidulafungin, caspofungin, and micafungin) and improved antifungal triazoles (posaconazole, ravuconazole, and voriconazole).[5,6]

Increased awareness among physicians, improved blood culture techniques, and the advent of high-resolution imaging techniques have had considerable impact on improving the clinical diagnosis of invasive fungal infections, and major progress has been made in harmonizing disease definitions, in defining paradigms for antifungal intervention, and in designing and implementing clinical trials.[7,8] Despite these advances, however, invasive fungal infections remain difficult to diagnose and to manage, and there is a continuing and urgent need for improved diagnosis, treatment, and prevention.

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