The frequency of invasive fungal infections continues to increase, both in the general population and in immunosuppressed patients (bone marrow transplant [BMT] recipients, patients with severe and prolonged neutropenia). Several factors are responsible for this increase in fungal infections, including increasing numbers of patients with impaired host defenses due to underlying diseases and/or immunosuppressive therapy. The inability to diagnose many invasive fungal infections in a timely manner continues to be a significant problem, and improved diagnostic methods are needed to permit early detection of infection. Despite the availability of several newer antifungal agents, therapy remains suboptimal, and much work remains to be done in defining the roles of established and novel modalities for treatment and prevention of infection.
Risk Factors and Frequency of Infection
Several risk factors account for the increased frequency of invasive fungal infections (Table 1). Moreover, multiple risk factors may be present in the same patient, which further increases risk. The most important risk factor for the development of fungal infection, particularly in patients with hematologic malignancies (with or without BMT), is severe and prolonged neutropenia. Chronic graft-vs-host disease, immunosuppressive therapy, multiple courses of broad-spectrum antibiotic therapy, the presence of vascular access catheters, parenteral nutrition, colonization at multiple sites, and prolonged stay in an intensive care unit are all associated with an increased frequency of invasive fungal infection. Finally, environmental exposure (hospital construction sites, contaminated cooling/heating systems) may also be a significant contributory factor. Prevention strategies, therefore, include the use of rooms equipped with high-efficiency particulate air (HEPA) filters to reduce the risk of environmental exposure.[1,2]
Data from the National Nosocomial Infections Surveillance (NNIS) system have best documented the changing epidemiology of nosocomial infections in US hospitals.[3] These data demonstrate that the rate of nosocomial fungal infections ranges from 2.0 to 3.8 infections per 1,000 hospital discharges from 1980 to 1990, with the proportion of fungal blood stream infections among all nosocomial bloodstream infections increasing from 5.4% to 9.9%.
The most marked increases occurred in surgical services (124%) and medical services (73%), and the rate of nosocomial candidemia increased by approximately 500% in large teaching hospitals, and by 219% and 370% in small teaching hospitals and large nonteaching hospitals, respectively. It is of interest to note that the recently reported Surveillance and Control of Pathogens of Epidemiological Importance (SCOPE) data from 49 US hospitals indicate that Candida bloodstream infections were nearly as common in the general hospital wards (43%) as in the intensive care unit (ICU) (57%).[4] In this survey, Candida species were the fourth most common bloodstream pathogen, accounting for 7.6% of infections, with such infections being associated with a crude mortality rate of 40%.
Spectrum of Infection
The most common yeast infection in the BMT setting (and in other neutropenic patients) is candidiasis. Prior to the use of fluconazole(Drug information on fluconazole) prophylaxis, the incidence of invasive candidal infection was between 10% and 20%, and the most common species was C albicans.[5] This has decreased substantially since fluconazole (Diflucan), and more recently itraconazole(Drug information on itraconazole) (Sporanox), has been used for prophylaxis. Many studies have documented the changing epidemiology of Candida infections with decreasing isolation rates for C albicans, and increasing isolation rates for other Candida species.[6,7]
In a study of 491 episodes of hematogenous candidiasis from the University of Texas M. D. Anderson Cancer Center, 42% of cases were caused by C albicans, 18% by C tropicalis, 17% by C parapsilosis, 11% by C glabrata, and the rest by other Candida species. Wide use of fluconazole appeared to be playing a major role in this observed shift. However, a more recent survey from the same institution of the distribution of Candida species in pediatric patients with candidemia revealed the same pattern (Table 2).[7,8] These patients do not receive fluconazole prophylaxis, are housed in a separate unit, and are cared for by staff dedicated to the pediatric unit. While antifungal prophylaxis—particularly with fluconazole—and nosocomial transmission have contributed to the changing epidemiology of infection, these data emphasize that other factors may also be involved.
Similarly, although A fumigatus has been the primary Aspergillus species, A terreus and other Aspergillus species appear to be increasing in frequency. Other less common molds, including Fusarium species, the Zygomycetes, Bipolaris and other dematiaceous fungi, and the yeast Trichosporon beigelii are being encountered with increasing frequency. The endemic mycoses (histoplasmosis, blastomycosis, cryptococcosis, coccidioidosis, etc) are seen sporadically in immunocompromised patients.
