Trichosporonosis
Also known as: Trichosporon Infection, Invasive Trichosporonosis
Trichosporon are basidiomycete yeasts, widespread in soil, water, decaying plant material, and animals, that are also part of the normal human skin, gut, and respiratory flora. They cause a range of infections: superficial (white piedra), allergic (summer type hypersensitivity pneumonitis), and invasive trichosporonosis, an opportunistic disseminated infection in patients with neutropenia, haematological malignancy, and intensive care stays. Invasive disease is rare but severe, and mortality is 50 to 80 percent.
The genus was reclassified into several genera (Trichosporon, Cutaneotrichosporon, and Apiotrichum), though the older names remain in clinical use.
| Species | Main diseases |
|---|---|
| Trichosporon asahii | Commonest cause of invasive infection, catheter infection, and urinary infection; hypersensitivity pneumonitis |
| Trichosporon inkin | White piedra of pubic hair and the genital area |
| Trichosporon ovoides | White piedra of scalp hair; sometimes invasive |
| Trichosporon mucoides (Cutaneotrichosporon mucoides) | Invasive infection, including central nervous system infection, and hypersensitivity pneumonitis |
| Trichosporon cutaneum (Cutaneotrichosporon cutaneum) | Superficial infection |
| Trichosporon asteroides, Trichosporon dermatis, Trichosporon loubieri, Trichosporon japonicum, Trichosporon faecale | Occasional invasive and superficial infections |
Species level identification needs sequencing of the intergenic spacer 1 region of the ribosomal DNA, which distinguishes species and genotypes. The internal transcribed spacer region is inadequate for separating the closely related species.
On Sabouraud dextrose agar at 25 to 37 degrees Celsius, Trichosporon forms cream, dry, wrinkled, or moist colonies within 2 to 5 days, which become radially furrowed with age. Microscopy shows true hyphae, pseudohyphae, blastoconidia, and rectangular arthroconidia. The yeast is urease positive, does not ferment sugars, is often resistant to cycloheximide (a point of difference from Cryptococcus), and grows at 37 degrees Celsius.
Virulence factors are biofilm formation on catheters and prosthetic surfaces, a capsule like glucuronoxylomannan layer (which explains cross reactivity with cryptococcal antigen), cell surface hydrophobicity and adherence, and secretion of proteases and lipases. The yeast is intrinsically resistant to echinocandins and has high amphotericin B MICs in many isolates.
| Setting | Notes |
|---|---|
| Haematological malignancy with neutropenia | The classic setting, especially acute leukaemia, and after stem cell transplant |
| Central venous catheter, parenteral nutrition, peritoneal dialysis catheter | Biofilm source |
| Intensive care, burns, major surgery | Prolonged hospitalisation, broad spectrum antibacterials, and indwelling devices |
| Breakthrough infection on antifungal prophylaxis or therapy | Echinocandins and amphotericin B are not active against Trichosporon |
| Corticosteroids and immunosuppression | Transplant, autoimmune disease |
| Prematurity and low birth weight | Neonatal catheter infections |
| HIV, diabetes, malignancy | Occasional |
| Prosthetic heart valves, intravenous drug use | Endocarditis |
Invasive trichosporonosis
The clinical picture resembles disseminated candidiasis, with persistent fever in a neutropenic patient, fungaemia, and multiorgan involvement.
- Fungaemia: positive blood cultures in most.
- Skin: erythematous or purpuric papules and nodules with central necrosis or ulceration in about 30 percent.
- Lung: infiltrates, pneumonia, and respiratory failure.
- Kidney: renal dysfunction and renal abscess, with positive urine culture.
- Liver and spleen: hepatosplenic lesions and raised liver enzymes.
- Eye: chorioretinitis and endophthalmitis.
- Central nervous system: meningitis and abscess.
- Cardiac: endocarditis, especially with prosthetic valves.
- Bone and joint: osteomyelitis and arthritis.
- Peritonitis: in peritoneal dialysis.
Other forms
- Urinary tract infection: catheter associated Trichosporon asahii infection, often with candiduria like presentation.
- Catheter related infection in non neutropenic patients.
- White piedra: soft, white to light brown nodules loosely attached to hair shafts of the scalp, beard, axillae, or pubic area, caused mainly by Trichosporon inkin and Trichosporon ovoides.
- Summer type hypersensitivity pneumonitis: a Japanese disorder caused by inhalation of Trichosporon asahii and Trichosporon mucoides in damp, warm houses in summer, with cough, fever, breathlessness, and diffuse infiltrates that recur each summer.
- Onychomycosis and skin disease from Trichosporon species occur occasionally.
| Condition | Points that separate it |
|---|---|
| Disseminated candidiasis | Germ tube or species differences, echinocandin response |
| Fusariosis | Skin lesions with positive blood cultures, hyaline moulds with phialides |
| Cryptococcosis | Capsule on microscopy; Trichosporon produces hyphae and arthroconidia |
| Disseminated bacterial infection | Positive bacterial cultures |
| Other yeasts (Rhodotorula, Saprochaete, Saccharomyces) | Culture and identification |
| Invasive aspergillosis, mucormycosis | Mould in culture or tissue |
| Hypersensitivity pneumonitis from other antigens | Antigen exposure and precipitins |
| Test | Interpretation |
|---|---|
| Blood and catheter tip culture | Detect yeast within 2 to 5 days; the laboratory should identify beyond "yeast" |
| Microscopy of tissue or skin biopsy | Hyphae, pseudohyphae, arthroconidia, and blastoconidia in tissue; periodic acid Schiff and Grocott methenamine silver stains |
| Identification | Matrix assisted laser desorption ionisation time of flight mass spectrometry with a library that includes Trichosporon; sequencing of the intergenic spacer 1 region for species |
| Cryptococcal antigen | Positive in many patients because of cross reaction with the glucuronoxylomannan like polysaccharide, so a positive result in a patient with a yeast fungaemia without cryptococcal features should not be accepted as cryptococcosis until culture identification |
| Beta D glucan | Often positive |
| Galactomannan | May be positive because of cross reaction |
| Susceptibility testing | By broth microdilution, with epidemiological cutoff values only; voriconazole and other azoles show activity |
| Hypersensitivity pneumonitis | Serum IgG antibodies to Trichosporon, inhalation provocation, and high resolution computed tomography with ground glass opacities |
| White piedra | Direct microscopy of hair shows hyphae, arthroconidia, and blastoconidia in a cement like sheath, and culture confirms |
Invasive trichosporonosis
- Voriconazole is the preferred agent: 6 mg per kg intravenously every 12 hours for 2 doses, then 4 mg per kg every 12 hours; the oral dose is 400 mg every 12 hours for 2 doses, then 200 mg every 12 hours in adults of 40 kg or more. Trough levels of 1 to 5.5 micrograms per mL are targeted.
- Alternatives: isavuconazonium sulphate 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses, then 372 mg once daily; posaconazole delayed release tablets 300 mg every 12 hours on day 1, then 300 mg daily; fluconazole 400 to 800 mg (6 to 12 mg per kg) daily for non critically ill patients or step down, and the response is less predictable.
- Amphotericin B has poor activity and is associated with breakthrough infection and poor outcomes, and it is not recommended alone. Combination of liposomal amphotericin B 5 mg per kg daily with voriconazole is used in refractory disease, with limited evidence.
- Echinocandins are inactive and are never used for treatment.
- Source control: remove central venous catheters and other infected devices, and debride or drain localised foci.
- Adjuncts: granulocyte colony stimulating factor in neutropenia, and recovery of the neutrophil count is the most important prognostic factor.
- Duration: at least 2 weeks after the last positive culture and resolution of symptoms, and until neutropenia resolves, extending to months for disseminated or deep disease.
- Urinary tract disease: removal of the catheter, and fluconazole 200 to 400 mg daily if treatment is needed (voriconazole is used when fluconazole fails).
Superficial disease
White piedra is treated by cutting or shaving the hair and applying topical azoles (ketoconazole 2 percent or miconazole 2 percent twice daily for 2 to 4 weeks) or ciclopirox 1 percent shampoo.
Hypersensitivity pneumonitis
Avoidance of the antigen (cleaning and drying the house and removing mould and moisture) is essential. Corticosteroids (prednisolone 0.5 to 1 mg per kg daily with taper over 4 to 8 weeks) are used for severe or progressive disease, and antifungal agents have no established role.
Monitoring and adverse effects
Voriconazole requires liver tests, trough levels, and monitoring for visual disturbance, hallucinations, photosensitivity, skin cancer on long courses, periostitis, and QT prolongation. Isavuconazole shortens the QT interval. Posaconazole needs levels (target above 1 microgram per mL). Interactions with calcineurin inhibitors, vincristine, and other agents need review.
Mortality in neutropenic patients is 70 to 80 percent, falling to about 40 to 50 percent when neutropenia resolves and therapy is early with an azole. Prevention focuses on minimising catheter exposure, reducing unnecessary broad spectrum antibacterial and antifungal exposure, and recognising that prophylaxis with echinocandins and amphotericin B does not protect against Trichosporon.
