The incidence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections may be broken into two broad categories: opportunistic and endemic. The most important agents of the opportunistic mycoses are Candida spp., Cryptococcus neoformans, Pneumocystis jirovecii, and Aspergillus spp. (although the list of potential pathogens is ever expanding); while the most commonly encountered endemic mycoses are due to Histoplasma capsulatum, Coccidioides immitis/posadasii, and Blastomyces dermatitidis. This review discusses the epidemiologic profiles of these invasive mycoses in North America, as well as risk factors for infection, and the pathogens' antifungal susceptibility.

Epidemiology of Invasive Mycoses in North America

Invasive fungal infections are increasingly common in the nosocomial setting Furthermore, because risk factors for these infections continue to increase in frequency, it is likely that nosocomial fungal infections will continue to increase in frequency in the coming decades The predominant nosocomial fungal pathogens include Candida spp, Aspergillus spp, Mucorales, Fusarium spp, and other molds, including Scedosporium spp These infections are difficult to diagnose and cause high morbidity and mortality despite antifungal therapy Early initiation of effective antifungal therapy and reversal of underlying host defects remain the cornerstones of treatment for nosocomial fungal infections In recent years, new antifungal agents have become available, resulting in a change in standard of care for many of these infections Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed

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Nosocomial fungal infections: epidemiology, diagnosis, and treatment

Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.

Infections Caused by Scedosporium spp.

Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi Melanin is a likely virulence factor for these fungi Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants Therapy varies depending upon the clinical syndrome Local infection may be cured with excision alone, while systemic disease is often refractory to therapy Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections

Melanized Fungi in Human Disease

With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.

An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients

Background. Unique characteristics, impact of therapy with antifungal agents, and outcome of infections with Scedosporium species were assessed in transplant recipients.Methods. The patients comprised a total of 80 transplant recipients with Scedosporium infections, including 13 patients from our institutions (University of Pittsburgh Medical Center [Pittsburgh, PA], University of Maryland [Baltimore], Duke University Medical Center [Durham, NC], Emory University [Atlanta, GA], and Hospital Gregorio Maranon [Madrid, Spain]) and 67 reported in the literature. The transplant recipients were compared with 190 non—transplant recipients with scedosporiosis who were described in the literature.Results. Overall, 69% of the infections in hematopoietic stem cell transplant (HSCT) recipients and 53% of the infections in organ transplant recipients were disseminated. HSCT recipients, compared with organ transplant recipients, were more likely to have infections caused by Scedosporium prolificans (P = .045), to have an earlier onset of infection (P = .007), to be neutropenic (P < .0001), and to have fungemia (P = .04). Time elapsed from transplantation to Scedosporium infection in transplant recipients has increased in recent years (P = .002). The mortality rate among transplant recipients with scedosporiosis was 58%. In a logistic regression model using amphotericin B as comparison treatment, voriconazole was associated with a trend towards better survival (odds ratio [OR], 10.40; P = .08). Presence of disseminated infection (OR, 0.20; P = .03) predicted lower survival, and receipt of adjunctive surgery as treatment (OR, 5.52; P = .02) independently predicted a better survival in this model.Conclusions. Scedosporium infections in transplant recipients were associated with a high rate of dissemination and a poor outcome overall. The use of newer triazole agents warrants consideration as a therapeutic modality for these infections.

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Infections Due to Scedosporium apiospermum and Scedosporium prolificans in Transplant Recipients: Clinical Characteristics and Impact of Antifungal Agent Therapy on Outcome

Kathleen Brennan

Papers

Infections Due to Scedosporium apiospermum and Scedosporium prolificans in Transplant Recipients: Clinical Characteristics and Impact of Antifungal Agent Therapy on Outcome