Invasive Fungal Pathogens: Current Epidemiological Trends

SUPPLEMENT ARTICLE Invasive Fungal Pathogens: Current Epidemiological Trends Michael A. Pfaller,1 Peter G. Pappas,2 and John R. Wingard3 1 Departments of Pathology and Epidemiology, Medical Microbiology Division, Roy J. and Lucille A. Carver College of Medicine and College of Public Health, University of Iowa, Iowa City; 2Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham; and 3Blood and Marrow Transplantation Program, Department of Medicine, Division of Hematology/Oncology, Shands Cancer Center, University of Florida, Gainesville The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades [1–5]. This increase in infection is associated with excessive morbidity and mortality [2, 5–11] and is directly related to the increasing numbers of patients who are at risk for the development of serious fungal infections, including patients undergoing blood and marrow transplantation (BMT), solid-organ transplantation, and major surgery (especially gastrointestinal surgery); patients with AIDS, neoplastic disease, and advanced age; patients receiving immunosuppressive therapy; and premature infants [2–5, 11–16]. Given the complexity of the population of patients who are at risk for infection and the diverse and increasing array of fungal pathogens (see table 1 of Alexander and Pfaller [17]), opportunistic mycoses pose considerable diagnostic and therapeutic challenges. The most well-known causes of opportunistic mycoses include Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus [1, 4–6, 18, 19]. The estimated annual incidence of invasive mycoses due to these pathogens is 72–228 infections per million pop- Reprints or correspondence: Dr. Michael A. Pfaller, Medical Microbiology Div., C606 GH, Dept. of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242 (). Clinical Infectious Diseases 2006; 43:S3–14  2006 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2006/4303S1-0002$15.00 ulation for Candida species, 30–66 infections per million population for C. neoformans, and 12–34 infections per million population for Aspergillus species [10, 11, 18, 20, 21]. In addition to these agents, the growing list of “other” opportunistic fungi is of increasing importance [1] (see table 1 of Alexander and Pfaller [17]). New and “emerging” fungal pathogens include species of Candida and Aspergillus other than C. albicans and A. fumigatus, opportunistic yeastlike fungi (e.g., Trichosporon and Rhodotorula species), the Zygomycetes, hyaline moulds (e.g., Fusarium and Scedosporium species), and a wide variety of dematiaceous fungi [1, 22]. Infections caused by these organisms range from catheter-related fungemia and peritonitis, to more localized infections (e.g., those involving the lungs, skin, and paranasal sinuses), to widespread hematogenous dissemination [1, 23]. Many of these fungi were previously thought to be nonpathogenic and are now recognized causes of invasive mycoses in immunocompromised patients. Some of these organisms are inherently resistant to standard azole, polyene, or echinocandin therapy and may require the use of alternative antifungal agents in addition to surgical management and reversal of the underlying impairment of host defenses. This article reviews selected aspects of the epidemiological profiles of the invasive mycoses and risk factors for infection with various fungal pathogens. The Epidemiology of Invasive Mycoses • CID 2006:43 (Suppl 1) • S3 Patient characteristics, antifungal prophylaxis, and other factors appear to have contributed to a change in the spectrum of invasive fungal pathogens. Infections with Candida glabrata, Aspergillus terreus, and nonAspergillus moulds appear to be on the rise, at least among certain populations. These species are resistant or less susceptible to some commonly used antifungal agents. Non-Aspergillus moulds are particularly lethal. This article reviews the spectrum of invasive mycoses and risk factors for infection with these pathogens. susceptibility of pathogens to antifungal agents is also discussed. Infections due to the endemic fungi and Cryptococcus species are not considered in this review. CANDIDA SPECIES INFECTION S4 • CID 2006:43 (Suppl 1) • Pfaller et al. Figure 1. Pathogens causing invasive fungal infections among solidorgan and hematopoietic stem cell transplant recipients. Data are from Pappas et al. [39]. PCP, Pneumocystis jiroveci (carinii). It is clear that the most important group of opportunistic fungal pathogens are the Candida species [1, 6, 11, 18, 22, 24–26]. Candida species account for 8%–10% of all nosocomial bloodstream infections (BSIs) and occur at a rate of 6–23 infections per 100,000 persons annually in the United States [2, 3, 6, 10, 11, 18, 20, 21, 26–29]. Between 1980 and the present, the frequency of Candida-associated BSI has increased steadily in hospitals of all sizes and in all age groups throughout the world [2, 6, 18, 26–38]. Notably, Candida species remain the most common fungal pathogens in intensive care unit (ICU), solidorgan transplantation, and BMT patient populations (figure 1) [2, 3, 6, 39]. The major concern with invasive candidiasis is that it is associated with an excess attributable mortality rate of 10%–49% [7, 9, 11, 40] and an excess length of hospital stay of 3–30 days [7, 9, 11, 40]. Furthermore, the excess cost attributable to candidemia in the United States approaches 1 billion dollars per year [9, 11, 41–43]. Although 1100 species of Candida have been described, only a few species have been implicated in clinical infections. C. albicans is the species most commonly recovered from clinical material and generally is responsible for 90%–100% of mucosal infections and for 50%–70% of episodes of candidemia [2, 3, 6, 18, 27, 44–46]. Approximately 95%–97% of all Candida-associated BSIs are caused by 5 species: C. albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei [1, 2, 6, 18]. Among these common species, only C. glabrata can be said to be truly “emerging” as a cause of BSI, because, in part, of its intrinsic and acquired resistance to azoles and other commonly used antifungal agents [1, 3, 18, 25, 27, 44–47]. Specific aspects of each of these species will be addressed below. The remaining 3%–5% of Candida-associated BSIs are caused by 12–14 different species, including Candida lusitaniae, Candida guilliermondii, and Candida rugosa (see table 1 of Alexander and Pfaller [17]) [1, 22, 48]. Although these species must be considered “rare” causes of candidiasis, several have been observed to occur in nosocomial clusters or to exhibit innate or acquired resistance to one or more established antifungal agents [1, 22, 49–55]. C. albicans. Among the various species of Candida capable of causing human infection, C. albicans predominates. Superficial infections of genital, oral, an (...truncated)