Trichosporon Infections

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Background

Trichosporon species are fungi that commonly inhabit the soil. They colonize the skin and gastrointestinal tract of humans.[1, 2] Long known as the cause of superficial infections such as white piedra, a distal infection of the hair shaft,[3] the genus is now the second most commonly reported cause of disseminated yeast infections in humans.[4]

All pathogenic members of the genus Trichosporon were once regarded as a single species, Trichosporon beigelii.[5] However, more recently, biochemical and morphologic differences within the genus have been described. T beigelii has been divided into distinct species, at least 9 of which have the potential to cause human disease: Trichosporon asahii (the most common cause of disseminated disease), Trichosporon inkin (the cause of white piedra[6] ), Trichosporon asteroides, Trichosporon cutaneum, Trichosporon mucoides, Trichosporon ovoides, Trichosporon pullulans, and, more recently, Trichosporon loubieri and Trichosporon japonicum.[7]

Multiple Trichosporon species, including T asahii and T mucoides, are associated with summer-type hypersensitivity pneumonitis in Japan.[8] Blastoschizomyces capitatus (formerly known as Trichosporon capitatus and also known as Geotrichum capitatum) is a closely related pathogen, and invasive B capitatus disease shares risk factors and clinical features with trichosporonosis.[9]

First described in the literature as a cause of invasive disease in 1970,[10] Trichosporon species are increasingly recognized as a cause of systemic illness in immunocompromised patients.[5] Hematologic malignancies are the best-described risk factors for trichosporonosis,[5] accounting for 63% of reported cases. Additional risk factors include corticosteroid use, hemochromatosis, other deficiencies of granulocyte function, and end-stage renal disease.[11, 12]

Pathophysiology

Trichosporon species are widely distributed in nature. Commonly isolated from soil and other environmental sources, Trichosporon is also a commensal in the human gastrointestinal and respiratory tracts.[1] Among the patients in a large Veterans Administration hospital, 0.8% of throat cultures and 3.1% of stool culture findings were positive for T beigelii.[13] A study of patients with cancer found a similar colonization rate of 3.7%.[14]

Despite this, Trichosporon infections are rare, even among patients with impaired host defenses. In one retrospective series, trichosporonosis (including B capitatus infections) developed in only 0.9% of patients with acute leukemia.[15] Of the remaining cases, corticosteroid use, solid tumors, HIV/AIDS, and intravascular devices, including catheters and prosthetic heart valves,[16] represented major risk factors.

These risk factors may work in conjunction; for example, chemotherapy used to treat hematologic malignancies can cause neutropenia and mucosal disruption. Trichosporon peritonitis is described in association with peritoneal dialysis catheters and is likely related to the combination of disrupted barrier immunity and immune dysfunction due to end-stage renal disease.[6] This invasion of mucosal barriers appears to be followed by vascular invasion and dissemination to other sites. Occasionally, Trichosporon infections are limited to a single organ system (eg, the lungs), but scattered visceral lesions similar to those observed in hepatosplenic candidiasis can also occur, often in patients who are recovering from neutropenia and cannot clear the infection.

Epidemiology

Frequency

United States

Trichosporon infections are rare. Approximately 400 cases of invasive Trichosporon (including B capitatus) infection have been reported in the world literature, although a true estimate of disease incidence cannot be calculated.

International

Despite the small number of cases, B capitatus may have a geographic predilection for Europe, with 86.9% of reported cases arising there (especially in Spain and Italy).

T asahii may be a more common cause of breakthrough fungemia in neutropenic patients from Japan than other regions.[17] , and this organism is the cause of summer-type hypersensitivity pneumonitis, a condition reported exclusively in Japan.[8]

Mortality/Morbidity

The mortality rate of acute disseminated trichosporonosis has been documented at between 50% and 80% in most case series.[18, 19, 20] In a more recent report, the 30-day all-cause mortality rate was 42% in patients with invasive disease.[21]

Sex

Trichosporonosis is much more common in males, with a 2:1 male-to-female predominance reported in multiple series.[11, 19]

Age

History

Physical

Causes

Most literature prior to 1995 refers to pathogenic Trichosporon species as T beigelii. Subsequent articles usually describe specific species under the newer nomenclature.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Grossly, infected tissues may contain micronodules (0.5-1.0 cm), occasionally surrounded by red rims. The GI tract may demonstrate ulceration and erosion associated with hemorrhage and hemorrhagic infarction.[5]

Microscopic examination of a nodule may reveal a necrotic center with fungal elements either in a starburst pattern or more loosely organized. Fungal elements may be observed invading the vasculature. Visualization of blastoconidia, arthroconidia, hyphae, and pseudohyphae in a histologic section supports the diagnosis of invasive Trichosporon infection.[5, 11] The cellular inflammation surrounding the fungal elements may vary, occasionally associated with hemorrhage. Granulomatous inflammation with multinucleated giant cells has been reported.[32]

Medical Care

Consultations

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. In general, empiric monotherapy should be avoided without specific testing of fungal sensitivity to available drugs.

Amphotericin B (Amphocin, Fungizone)

Clinical Context:  Amphoteric polyene antifungal with activity against many fungal pathogens. Administered in solution only and is well known for a variety of toxic side effects. May be injected intrathecally or into a joint space, or it may be used as an irrigant, although it is usually administered IV. Dose should be adjusted for the indication. For trichosporonosis, high doses are required.

Amphotericin B, liposomal (AmBisome)

Clinical Context:  Novel lipid formulations of amphotericin B that deliver higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium).

At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B may reside in ability to cause auto-oxidation of cell membranes.

Voriconazole (Vfend)

Clinical Context:  A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Commonly used in the treatment of aspergillosis, invasive candidiasis, and neutropenic fever. Has excellent MICs against Trichosporon species and has occasionally been effective as monotherapy.

Posaconazole (Noxafil)

Clinical Context:  Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

Fluconazole (Diflucan)

Clinical Context:  Triazole derivative with high enteral bioavailability used for Candida infections and infections with endemic mycoses. Also useful for Trichosporon infections. Dose depends on the indication. For trichosporonosis, the dose should be the maximum dosage.

Flucytosine (Ancobon)

Clinical Context:  Pyrimidine analog available enterally or IV for use against a variety of fungal pathogens but is not generally used as monotherapy owing to emergence of resistance during therapy. Well absorbed orally but should be administered IV to critically ill patients.

Caspofungin (Cancidas)

Clinical Context:  Routinely used to treat refractory invasive aspergillosis and invasive candidiasis. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.

Micafungin (Mycamine)

Clinical Context:  Member of new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Inhibits synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells.

Approved indications include (1) prophylaxis of candidal infections in patients undergoing hematopoietic stem cell transplantation and (2) treatment of esophageal candidiasis.

Further Inpatient Care

Prognosis

Author

Tyler E Warkentien, MD, Staff physician, Department of Infectious Diseases, Naval Naval Medical Center, Bethesda, MD

Disclosure: Nothing to disclose.

Coauthor(s)

Braden R Hale, MD, MPH, Assistant Clinical Professor, Department of Internal Medicine, University of California at San Diego; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Naval Medical Center at San Diego

Disclosure: Nothing to disclose.

Ryan C Maves, MD, Staff Physician, Division of Infectious Diseases, Naval Medical Center San Diego, California; Assistant Professor of Medicine and Preventive Medicine, Uniformed Services University, Bethesda, Maryland

Disclosure: Nothing to disclose.

Specialty Editors

Jeffrey M Zaks, MD, Clinical Associate Professor of Medicine, Wayne State University School of Medicine; Vice President, Medical Affairs, Chief Medical Officer, Department of Internal Medicine, Providence Hospital

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

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