AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Trichosporon species are soil inhabitants and common colonizers of human skin and GI tracts. Previously, all pathogenic members of the genus Trichosporon were regarded as a single species, Trichosporon beigelii. More recently, biochemical and morphologic differences within the genus have been appreciated. T beigelii has now been divided into distinct species, at least 8 of which have the potential to cause human disease: Trichosporon asahii, Trichosporon inkin, Trichosporon asteroides, Trichosporon cutaneum, Trichosporon mucoides, Trichosporon ovoides, Trichosporon pullulans, and, more recently, Trichosporon loubieri.

T asahii and T inkin have been most closely implicated with human infections. White piedra, a distal infection of the hair shaft, appears to be due to T inkin, as are other superficial infections such as dermatomycosis, onychomycosis, and otomycosis. Multiple species, including T asahii and T mucoides, are associated with summer-type hypersensitivity pneumonitis, which is commonly found in Japan.

First described in the 1960s as a cause of pulmonary mycosis, Trichosporon causes severe disseminated disease in immunocompromised individuals. T asahii is responsible for most of the invasive infections known collectively as trichosporonosis. Invasive disease caused by Blastoschizomyces capitatus, (formerly Trichosporon capitatus and also known as Geotrichum capitatum) is included in this definition. Hematologic malignancies are the strongest identified risk factor for trichosporonosis, but corticosteroid use, hemochromatosis, deficiencies of granulocyte function, and end-stage renal disease have all been implicated in its development.

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. 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, and other studies report similar rates.

Despite this, infection with Trichosporon is rare, even in patients with impaired host defenses. In one retrospective study, trichosporonosis (including trichosporonosis caused by B capitatus) developed in only 0.9% of patients with acute leukemia. Hematologic malignancies were associated with 62.8% of reported cases of trichosporonosis. Of the remaining cases, corticosteroid use, solid tumors, HIV/AIDS, and intravascular devices, including catheters and prosthetic heart valves, represented major risk factors. Hemochromatosis is a separate risk factor for trichosporonosis; increased concentrations of iron appear to favor the growth of Trichosporon.

Risk factors can work in conjunction; for example, cytotoxic-induced chemotherapy 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 associated with end-stage renal disease. Invasion of mucosal barriers appears to be followed by vascular invasion and local spread, which are then followed by dissemination to other sites. The liver, spleen, kidney, lungs, eye, brain, GI tract, and skin are frequently involved in the acute disseminated syndrome. In chronic forms, patients who are recovering from neutropenia cannot rid themselves of the organism and develop scattered visceral lesions similar to those observed in hepatosplenic candidiasis. Occasionally, infection may be limited to a single organ system (eg, lungs).

Frequency

United States

This disease is rare. Approximately 400 cases of invasive Trichosporon (including B capitatus) infection had been reported in the world literature, although a true estimate of disease incidence cannot be calculated. In the highest risk group (patients with hematologic malignancy), fewer than 0.1% of patients appear to contract the illness.

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).

Mortality/Morbidity

• Two common variants of Trichosporon infection occur in humans: (1) a disseminated acute-onset form associated with high mortality and (2) a more indolent form that causes visceral lesions and is associated with lower mortality. Acute trichosporonosis generally disseminates to multiple organs and is fatal in more than 60% of patients. In more indolent forms, mortality rates are significantly lower but may require prolonged administration of antifungal agents.

Sex

• Invasive disease due to Trichosporon species occurs significantly more often in males, with a 2:1 male-to-female predominance being reported in multiple series. In one series, 47 of 67 (70%) cases occurred in males, with 138 of 205 (67%) cases occurring in males in a separate series. The prevalence of white piedra is also greater in male patients.

Age

• Diseases that confer susceptibility to Trichosporon infections are most prevalent in adults, and most of the reported cases occur in adults.
• A scattered number of neonatal invasive Trichosporon infections have been reported.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• The typical patient presents with neutropenia and fever, usually in the setting of cytotoxic chemotherapy for a hematologic malignancy. The patient may also have an indwelling intravascular or peritoneal catheter.
• A history of corticosteroid use is common, often as part of a chemotherapeutic regimen for leukemia or lymphoma. As with patients who have invasive candidiasis, broad-spectrum antibiotic use without improvement may be included in the history. However, prophylactic antifungal therapy, such as amphotericin B or echinocandins, may have also been administered without benefit.
• White piedra is not a significant risk factor.
• Elicit information about the presence of hemochromatosis or prosthetic heart valves from patients with invasive Trichosporon infection.
• Patients may have a variable constellation of historical features, depending on the organs involved.
• Patients able to relate a history generally note the presence of fever and, possibly, chills.
• In patients with pulmonary infiltrates, symptoms of respiratory insufficiency may be present.
• Flank pain and a history of hematuria may signal renal involvement.
• A significant number of patients note skin involvement. (The presence of skin lesions may represent a site for biopsy, aiding in the diagnosis.)
• GI lesions from the oropharynx to the rectum may be a source of complaint.
• Patients undergoing peritoneal dialysis may present with abdominal pain, abdominal distension, and cloudy peritoneal fluid.

Physical

• Cutaneous findings
• • These occur in a third of patients with disseminated disease.
  • A variety of cutaneous lesions are described. The most common lesions are nontender, erythematous nodules of varying number, which are located mainly on the extremities but are also found on the trunk and face. The lesions may become ulcerated, possibly developing an appearance similar to that of ecthyma gangrenosum.
• Ocular involvement is well-described and occurs in the uveal tissues.
• Pulmonary infiltrates are common, occurring in about 25% of patients, with no specific pattern of involvement. Hypoxia has been described in association with these lesions. An isolated pulmonary infiltrate may be the only demonstrable manifestation of Trichosporon in some patients.
• Flank tenderness or hematuria may be present and suggests possible renal involvement, which is common.
• Lesions may be found along the entire length of the GI tract, usually in the form of erosions or ulcers.
• A subset of patients have infection localized to only one organ, and fungemia may not occur in all of these patients. Localized disease has been described in the lungs, peritoneum, eye, brain, and stomach.

Causes

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

• Etiologic agents, in order of reported frequency
• • T asahii
  • B capitatus
  • T inkin
• Trichosporon is a normal colonizer of mucous membranes in the GI and respiratory epithelium and skin; invasive disease usually requires significant host compromise of both anatomic and neutrophilic defenses.
• In nearly all patients, the source of the invasive organism is the host flora. Trichosporon is not typically isolated from hospital environments, although outbreaks due to contaminated hospital equipment have been reported. Unlikely sources of nosocomial spread, such as infected urinary catheters that lead to aerosolization of the fungus and airborne transmission, have been described.
• Risk factors
• • Among host factors, neutropenia is the greatest single risk factor; however, most exposed neutropenic patients remain uninfected, and a significant number of infected patients are not neutropenic.
  • Corticosteroid use is another significant risk factor. Patients receiving steroids for a variety of reasons without other predisposing factors have been infected.
  • Hemochromatosis is another risk factor, and the Trichosporon organism's growth is enhanced by supplemental iron.
  • Prosthetic heart valves have been infected with Trichosporon.
  • Infections are reported among patients infected with HIV, patients undergoing renal replacement therapy, and neonates.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

• Trichosporon infections have varying differentials.
• • Candida species
  • Fusarium sepsis
  • Aspergillus species
  • Other fungal infections
• Pulmonary infiltrates
• • Acute respiratory distress syndrome
  • Candida species
  • Fusarium
  • Aspergillus
  • Other fungi
• Renal lesions
• Cryptococcus neoformans
• Bacterial infection
• Other fungi
• In the immunocompromised patient, Trichosporon infection can coexist with other fungal, bacterial, or viral pathogens.
• Because of the cross-reactivity between Trichosporon and latex agglutination tests for the serum cryptococcal antigen, an latex agglutination test positive for cryptococcus may suggest trichosporonosis when other data are conflicting.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The diagnosis is usually confirmed by a positive blood culture result obtained in the evaluation of a febrile (typically neutropenic) patient.
• Important laboratory tests include blood culture sets, blood chemistries and hepatic transaminases, alkaline phosphatase, bilirubin, lactic acid dehydrogenase (LDH), and urinalysis with urine culture.
• Urine may be the first body fluid to grow Trichosporon in the setting of disseminated disease, and it should not be presumed to be a contaminant or colonizer in the high-risk host (ie, in the setting of neutropenic fever).
• Trichosporon and C neoformans are closely related organisms and share a number of surface antigens. As such, the latex agglutination test results for serum cryptococcal antigen is often positive in the setting of disseminated trichosporonosis (except trichosporonosis due to B capitatus). This widely used, rapid, and inexpensive test may provide an early clue about a Trichosporon infection. Because of changes in cell wall conformation, these test results may become negative during antifungal therapy, but newly negative test results do not imply a response to therapy.
• Investigational methods of rapid diagnosis, such as polymerase chain reaction (PCR)–based assays and flow cytometry, are in development but are not yet widely available.

Imaging Studies

• Radiologic evaluation should include a chest radiograph and CT scans of the abdomen and pelvis. A CT scan of the chest is also frequently useful in the evaluation of the pulmonary infiltrate in the patient population at risk for Trichosporon infection, but confirmation of the diagnosis should rely on a tissue sample or on another useful clinical sample. Depending on the clinical picture, a CT scan or MRI of the brain may be indicated.
• Endocarditis is rarely reported but is associated with high mortality rate (82% in a single series). Patients with prosthetic heart valves or persistently positive blood culture results should undergo echocardiography.

Procedures

• When pulmonary infiltrates are present, bronchoscopy is a useful means of obtaining samples if the patient can tolerate the procedure. Positive culture results from a bronchial lavage supports the diagnosis.
• Biopsy
• • Open-lung biopsy may be required for definitive diagnosis because of the large number of viral, bacterial, protozoal, and fungal pathogens that can cause disease in patients with pulmonary infiltrates.
  • Lesions of the GI tract may be accessible for biopsy and may yield a diagnosis before blood cultures return positive findings.
  • Skin lesions occur in roughly 10% of patients with disseminated disease. Biopsy of suspicious lesions in immunocompromised patients with fever may facilitate early diagnosis.
• Liver lesions or other visceral lesions may also require biopsy for diagnosis and optimal management.

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.

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, and hyphae in a histologic section supports the diagnosis of invasive Trichosporon infection. The cellular inflammation surrounding the fungal elements may be variable, occasionally associated with hemorrhage. Granulomatous inflammation with multinucleated giant cells has been reported.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• High-dose amphotericin B deoxycholate (1-1.5 mg/kg/d) has been the historic cornerstone for treatment of invasive disease due to Trichosporon. Because of high rates of resistance to amphotericin B and the toxicity of this regimen, alternate therapies are often necessary. Lipid preparations of amphotericin B (eg, liposomal amphotericin B 5 mg/kg/d) are commonly used in place of amphotericin B deoxycholate. However, treatment failures have also been reported with this regimen. The addition of high-dose fluconazole (800-1600 mg/d) and 5-flucytosine to amphotericin B has improved clinical response rates.
• Novel antifungal therapies have improved the management of trichosporonosis. The echinocandins (caspofungin, micafungin, anidulafungin) act by inhibiting the beta-glucan cell wall of Trichosporon. Caspofungin and micafungin have poor in vitro activity against Trichosporon when used alone. One report has described successful treatment of T inkin peritoneal catheter–associated peritonitis using caspofungin monotherapy. More recently, however, cases of breakthrough T asahii infections have been reported in patients with hematologic malignancies receiving micafungin for empiric treatment of neutropenic fever. Early data show efficacy when echinocandins are combined with amphotericin B. Micafungin and amphotericin B are synergistic against Trichosporon in vitro. One in vivo murine model of trichosporonosis showed a significant reduction in fungal burden in multiple infected organ systems when amphotericin B was combined with micafungin.
• The newer triazoles (eg, voriconazole, posaconazole, ravuconazole) show excellent in vitro activity against Trichosporon. Posaconazole (Noxafil) was recently approved by the US Food and Drug Administration for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression. Successful clearance of fungemia with voriconazole has been reported in one patient in whom liposomal amphotericin B treatment was failing.
• Combination therapy should be the cornerstone of treatment for Trichosporon infections. The combination of high-dose amphotericin B (deoxycholate or liposomal) with 5-flucytosine and fluconazole is the regimen with the most experience; however, this also has a high failure rate. Amphotericin B plus micafungin or caspofungin are potentially promising regimens, but human data are currently lacking.
• Regardless of the therapeutic options, response may not be optimal until the patient recovers from the immunocompromised state, which is usually neutropenia. Consider the addition of granulocyte colony-stimulating factor (G-CSF) in patients with neutropenia. Reduce the steroid dose as much as possible in patients receiving high-dose corticosteroids. Persistence of positive blood culture findings on amphotericin B monotherapy suggests resistance, and modification of the regimen is indicated. Catheter-associated infections, such as peritonitis in patients undergoing peritoneal dialysis, generally require removal of the catheter.
• In patients who do not respond to high-dose amphotericin B, add high-dose fluconazole and flucytosine (5-FC). Administer fluconazole at the highest doses. Unfortunately, all these therapies have significant failure rates in patients with neutropenia. Levels of 5-FC must be carefully monitored. Do not use 5-FC if levels cannot be measured expeditiously. Rifampin may have substantial in vitro synergy with amphotericin B, but no evidence supports its use in most situations. Liposomal amphotericin has been successfully used in trichosporonosis but, in theory, may not offer a significantly greater efficacy over standard therapy. Miconazole has significant in vitro activity; however, this does not translate to useful in vivo results, and it should not be used.

Consultations

• Patients with trichosporonosis are often critically ill because of their infection and their frequent underlying illnesses. ICU admission is warranted in most cases.
• Consultation with an ophthalmologist is generally advised for diagnostic purposes and to evaluate for fungal retinitis. Proper management should include input from infectious disease physicians.
• Because of the many organ systems involved, input from a number of other specialties may be required. Pulmonary, gastroenterology, dermatology, and general surgery physicians commonly assist in the diagnosis and management of these patients.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Drug Category: Antifungal agents

Antifungal drugs work by exploiting the differences between fungal and mammalian cells. Specific drugs act by inhibiting membrane ergosterol synthesis (azoles), binding ergosterol to depolarize the cell (amphotericin B), or inhibiting nucleic acid metabolism (5-flucytosine).

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Monitor carefully, preferably in the ICU, until recovery of an adequate neutrophil count. Continue potent antifungal therapy during the period of neutropenia and after recovery of neutrophil count until the resolution of symptoms.
• Monitor blood cultures, urine cultures, and cutaneous or ocular lesions, along with renal and hepatic panel blood chemistries.
• CT scans of the abdomen and pelvis are indicated in most patients for initial evaluation and should be periodically repeated to indicate possible evolution of disease. For example, the lesions of hepatosplenic disease may become visible only after recovery of neutrophils.
• The patient should remain on therapy until clinically stable and afebrile with the resolution of all visceral lesions.

Prognosis

• Prognosis for acute disseminated infection is poor, unless recovery of neutrophils occurs.
• Prognosis for indolent or localized infection is better than for disseminated disease.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Several pitfalls are associated with the diagnosis and management of patients infected with Trichosporon.
• • Relying on a primary regimen that contains only a single drug may be problematic, as could the use of an echinocandin as monotherapy.
  • Failure to recognize the significance of clinical isolates of Trichosporon could result in litigation.
  • Recognizing that patients who survive trichosporonosis, particularly hepatosplenic disease, may develop recurrent disease if the host immune system is suppressed again may prevent medicolegal problems.
  • If only histologic tissue is used in the diagnosis of trichosporonosis, take great care in the interpretation of the results, since species identification can be difficult.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Antachopoulos C, Papakonstantinou E, Dotis J, et al. Fungemia due to Trichosporon asahii in a neutropenic child refractory to amphotericin B: clearance with voriconazole. J Pediatr Hematol Oncol. May 2005;27(5):283-5.
• Assaf RR, Weil ML. The superficial mycoses. Dermatol Clin. Jan 1996;14(1):57-67. [Medline].
• Bassetti M, Bisio F, Di Biagio A. Trichosporon asahii infection treated with caspofungin combined with liposomal amphotericin B. J Antimicrob Chemother. Aug 2004;54(2):575-7.
• Bodey GP. Dermatologic manifestations of infections in neutropenic patients. Infect Dis Clin North Am. Sep 1994;8(3):655-75. [Medline].
• Diaz MR, Fell JW. High-throughput detection of pathogenic yeasts of the genus trichosporon. J Clin Microbiol. Aug 2004;42(8):3696-706.
• Keay S, Denning DW, Stevens DA. Endocarditis due to Trichosporon beigelii: in vitro susceptibility of isolates and review. Rev Infect Dis. May-Jun 1991;13(3):383-6. [Medline].
• Kontoyiannis DP, Torres HA, Chagua M. Trichosporonosis in a tertiary care cancer center: risk factors, changing spectrum and determinants of outcome. Scand J Infect Dis. 2004;36(8):564-9.
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• Madariaga MG, Tenorio A, Proia L. Trichosporon inkin peritonitis treated with caspofungin. J Clin Microbiol. Dec 2003;41(12):5827-9.
• Matsue K, Uryu H, Koseki M. Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin. Clin Infect Dis. Mar 15 2006;42(6):753-7.
• Pini G, Faggi E, Donato R. Isolation of Trichosporon in a hematology ward. Mycoses. Jan 2005;48(1):45-9.
• Ramos JM, Cuenca-Estrella M, Gutierrez F. Clinical case of endocarditis due to Trichosporon inkin and antifungal susceptibility profile of the organism. J Clin Microbiol. May 2004;42(5):2341-4.
• Rodriguez-Tudela JL, Diaz-Guerra TM, Mellado E. Susceptibility patterns and molecular identification of Trichosporon species. Antimicrob Agents Chemother. Oct 2005;49(10):4026-34.
• Serena C, Pastor FJ, Gilgado F. Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis. Antimicrob Agents Chemother. Feb 2005;49(2):497-502.
• Tashiro T, Nagai H, Kamberi P, et al. Disseminated Trichosporon beigelii infection in patients with malignant diseases: immunohistochemical study and review. Eur J Clin Microbiol Infect Dis. Mar 1994;13(3):218-24. [Medline].
• Vartivarian SE, Anaissie EJ, Bodey GP. Emerging fungal pathogens in immunocompromised patients: classification, diagnosis, and management. Clin Infect Dis. Nov 1993;17 Suppl 2:S487-91. [Medline].
• Walling DM, McGraw DJ, Merz WG, et al. Disseminated infection with Trichosporon beigelii. Rev Infect Dis. Sep-Oct 1987;9(5):1013-9. [Medline].
• Walsh TJ. Trichosporonosis. Infect Dis Clin North Am. Mar 1989;3(1):43-52. [Medline].
• Walsh TJ, Melcher GP, Rinaldi MG, et al. Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. J Clin Microbiol. Jul 1990;28(7):1616-22. [Medline].
• Walsh TJ, Melcher GP, Lee JW, Pizzo PA. Infections due to Trichosporon species: new concepts in mycology, pathogenesis, diagnosis and treatment. Curr Top Med Mycol. 1993;5:79-113. [Medline].

Article Last Updated: Sep 29, 2006