eMedicine Specialties > Infectious Diseases > Fungal Infections

Trichosporon Infections

Tyler E Warkentien, MD, Fellow, Department of Infectious Diseases, Naval Medical Center, San Diego
Ryan C Maves, MD, Consulting Staff and Director, Bacteriology Program, United States Naval Medical Research Center Detachment, Lima, Peru; 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

Updated: Nov 4, 2009

Introduction

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 piedra⁶ ), 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

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.¹² A study of patients with cancer found a similar colonization rate of 3.7%.¹³

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.¹⁴ Of the remaining cases, corticosteroid use, solid tumors, HIV/AIDS, and intravascular devices, including catheters and prosthetic heart valves,¹⁵ 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.

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.¹⁶ , 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.^17,18,19 In a more recent report, the 30-day all-cause mortality rate was 42% in patients with invasive disease.²⁰

Sex

Trichosporonosis is much more common in males, with a 2:1 male-to-female predominance reported in multiple series.^11,18

Age

• Diseases that confer susceptibility to Trichosporon infections are most prevalent in adults, with a median age of 44 years in one report.¹⁸
• A small number of neonatal and pediatric invasive Trichosporon infections have been reported.²¹

Clinical

History

• The typical patient with trichosporonosis 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 in patients with invasive candidiasis, empiric broad-spectrum antibacterial therapy without clinical 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.¹
• Past medical history may include hemochromatosis¹¹ or prosthetic heart valve placement.¹⁵
• Patients with trichosporonosis may have a variable constellation of historical features, depending on the organs involved, and often have fever and chills.
• Pulmonary infiltrates and respiratory symptoms may be present.
• Flank pain, azotemia, hematuria, or red blood cell casts may signal renal involvement.¹¹
• Skin involvement often begins as a discrete maculopapular rash and may progress to purpuric or hemorrhagic manifestations.¹¹ (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 symptomatic.
• Patients undergoing peritoneal dialysis may present with abdominal pain, abdominal distension, and cloudy peritoneal fluid.^6,22
• Chorioretinitis¹¹ and spondylodiscitis have also been described.²³

Physical

• Cutaneous findings occur in one third of patients with disseminated Trichosporon disease.²⁴ The most commonly described lesions are nontender erythematous nodules of varying number,²¹ which are located mainly on the extremities but are also found on the trunk and face. The lesions may become ulcerated,²⁴ with 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 but with no specific pattern of involvement.¹ Hypoxia has been described in association with these lesions. An isolated pulmonary infiltrate may be the only demonstrable manifestation of trichosporonosis in some patients.
• Flank tenderness or hematuria may be present and suggests 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.
• Some patients have infection localized to only one organ, and fungemia may not occur in all of these patients.¹ Localized disease has been described in the lungs, peritoneum,⁶ 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, include the following:
  • T asahii
  • B capitatus (Trichosporon capitum)
  • T inkin
  • Trichosporon dermatis
  • Trichosporon montevideense
• Trichosporon is a normal colonizer of mucous membranes in the GI and respiratory epithelium, as well as the 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’s flora. Trichosporon is not often isolated from hospital environments, although outbreaks due to contaminated hospital equipment have been reported. Unlikely sources of nosocomial spread, such as infected urinary catheters and associated aerosolization of the fungus, have been described.²⁵
• Risk factors include the following:
  • Neutropenia is the greatest single risk factor.⁵
  • Additional risk factors include corticosteroid use, cytotoxic chemotherapy, diabetes,²⁶ and hemochromatosis.¹¹
  • Trichosporonosis has been described in patients with prosthetic heart valves,²⁷ those with HIV infection, patients on dialysis, and neonates.
  • Many of these risk factors directly contribute to deficiencies in the host immune system. Hemochromatosis may be a risk factor owing to excess iron stores, as in vitro data suggest improved fungal growth in iron-supplemented media.¹¹

Differential Diagnoses

Other Problems to Be Considered

• In the immunocompromised patient, Trichosporon infection can coexist with other fungal, bacterial, or viral infections.
• Because of the cross-reactivity between Trichosporon and latex agglutination tests for the serum cryptococcal antigen, a positive test may suggest trichosporonosis when other data are conflicting.⁵
• Patients with trichosporonosis may have candidemia during same hospital visit.²⁰

Workup

Laboratory Studies

• The diagnosis of trichosporonosis 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 cultures may be the first to grow Trichosporon in the setting of disseminated disease,¹³ and it should not be presumed to be a contaminant or colonizer in the high-risk host (ie, in the setting of neutropenic fever).¹
• Trichosporon and Cryptococcus 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 trichosporonosis⁵ (except trichosporonosis due to B capitatus⁹ ). 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.¹
• Investigational methods of rapid molecular diagnostics, such as DNA-based microarrays,²⁸ polymerase chain reaction (PCR), and pyrosequencing,²⁹ are in development but are not yet widely available for clinical use.³⁰

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^15,27 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

• Bronchoscopy: 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 support the diagnosis.²¹
• 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 trichosporonosis. 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.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.³¹

Treatment

Medical Care

• The newer triazoles (eg, voriconazole, posaconazole, ravuconazole) show excellent in vitro activity against Trichosporon.^15,20,21 In particular, voriconazole seems to have better in vitro activity than amphotericin B.^20,32 Indeed, successful clearance of fungemia with voriconazole has been reported when liposomal amphotericin B treatment was failing.²¹ Posaconazole is 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 and has activity against Trichosporon, although human clinical data are both limited and mixed in terms of results.^33,34
• High-dose amphotericin B deoxycholate (1-1.5 mg/kg/d) historically has been the most common treatment for invasive trichosporonosis, but many breakthrough cases have occurred on this therapy.^19,35 Because of high rates of resistance to amphotericin B³² 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, although treatment failures have also been reported with these agents.¹⁷ B capitatus infectionsappear to respond better to amphotericin B than those due to Trichosporon species.¹⁹
• The echinocandins caspofungin and micafungin have poor in vitro activity against Trichosporon when used alone.¹⁶ One report describes successful treatment of T inkin peritoneal catheter–associated peritonitis using caspofungin monotherapy.⁶ However, cases of breakthrough T asahii infections have been reported in patients with hematologic malignancies receiving micafungin¹⁶ and caspofungin²⁶ for empiric treatment of neutropenic fever. Combination therapy with caspofungin and liposomal amphotericin B may be effective,¹⁷ and micafungin and amphotericin B appear 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.
• Combination therapy should be the cornerstone of treatment for trichosporonosis. The combination of high-dose amphotericin B (deoxycholate or liposomal) with either or both 5-flucytosine or fluconazole is commonly prescribed, although failure rates remain high. Amphotericin B plus an echinocandin is a potentially promising regimen, and synergy has been suggested in a murine model,³⁶ but human data are currently lacking.
• Regardless of the therapeutic options, patients’ clinical responses may not be optimal until they recover from their predisposing immunocompromised states. Possible strategies include the addition of granulocyte colony-stimulating factor (G-CSF) in patients with neutropenia⁵ and the reduction of glucocorticoid doses as much as possible in patients receiving these agents. 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, an azole or flucytosine (5-FC) should be added. Unfortunately, all of 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. Liposomal amphotericin has been successfully used in trichosporonosis but may not necessarily offer 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 an infectious disease specialist.
• Because of the many organ systems involved, input from a number of other specialists may be required. Pulmonologists, gastroenterologists, dermatologists, and general surgeons commonly assist in the diagnosis and management of patients with trichosporonosis.

Medication

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.

Antifungal Agent, Systemic

Amphotericin B (Amphocin, Fungizone)

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.

Dosing

Adult

1.0-1.5 mg/kg/d IV qd

Pediatric

Administer as in adults

Interactions

Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

Amphotericin B, liposomal (AmBisome)

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.

Dosing

Adult

3-5 mg/kg/d IV over approximately 120 min

Pediatric

Administer as in adults

Interactions

Antineoplastic agents may enhance the potential of amphotericin B in renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor renal function, serum electrolytes such as magnesium and potassium, liver function, CBC count, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

Voriconazole (Vfend)

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.

Dosing

Adult

Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h; switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
<40 kg: Average maintenance dose is 100 mg PO q12h (may increase to 150 mg PO q12h)

Pediatric

Not established

Interactions

CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG CoA inhibitors, benzodiazepines, calcium channel blockers)

Contraindications

Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson Syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc

Posaconazole (Noxafil)

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.

Dosing

Adult

200 mg (5 mL) PO QID with food or liquid nutritional supplement to enhance absorption; may transition to 400 mg PO bid after disease stabilization

Pediatric

<13 years: Not established
>13 years: Administer as in adults

Interactions

Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor
UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk)
Inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine (withdrawn from US market), astemizole (withdrawn from US market), cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)

Contraindications

Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine [withdrawn from US market], astemizole [withdrawn from US market], cisapride, pimozide, halofantrine, quinidine)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding

Fluconazole (Diflucan)

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.

Dosing

Adult

800-1200 mg PO or IV daily; administer IV in critically ill patients or any other patient in whom GI function is impaired

Pediatric

16 mg/kg/d loading dose PO; follow with 8 mg/kg/d maintenance; administer IV in the critically ill patient or any other patient in whom GI function is impaired

Interactions

Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with chronic coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose for renal insufficiency; monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis and fulminant hepatic failure (including death), with underlying medical conditions, such as AIDS or a malignancy, and while taking multiple concomitant medications; not recommended for nursing mothers; convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents

Flucytosine (Ancobon)

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.

Dosing

Adult

150 mg/kg/d PO/IV divided qid; dose may require adjustment depending on serum levels

Pediatric

50-100 mg/kg/d PO/IV divided qid

Interactions

Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Flucytosine levels must be monitored; bone marrow suppression may occur; hematologic and hepatic function should be monitored during therapy

Caspofungin (Cancidas)

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.

Dosing

Adult

70 mg IV once, followed by 50 mg IV q24h

Pediatric

Not established

Interactions

Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate pre-existing renal dysfunction or myelosuppression

Micafungin (Mycamine)

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.

Dosing

Adult

50 mg IV q24h infused over 1 h (higher doses, up to 150 mg IV q24h, used for other indications, including esophageal candidiasis)

Pediatric

Not established

Interactions

Increases sirolimus and nifedipine AUC approximately 20%

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects may include headache, nausea, vomiting, and abdominal pain; other adverse effects include skin rash, delirium, phlebitis, shock, leukopenia, and hyperbilirubinemia; rare cases of elevated hepatic enzyme, BUN, and creatine levels have been reported; transient acute intravascular hemolysis and hemoglobinuria may occur; do not mix or infuse in same IV line with other medications because precipitate forms with other commonly used medications (flush existing IV line with 0.9% NaCl before and after infusion); protect from light following dilution

Follow-up

Further Inpatient Care

• Patients with trichosporonosis should be monitored carefully, preferably in the ICU, until recovery of an adequate neutrophil count. Continue active 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 scanning of the abdomen and pelvis is indicated in most patients for initial evaluation and should be periodically repeated to monitor the progress 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

• The prognosis of acute disseminated Trichosporon infection is poor, unless recovery of neutrophils occurs.
• The prognosis of indolent or localized infection is better than that of disseminated disease.

Miscellaneous

Medicolegal Pitfalls

• Relying on a primary regimen that contains only a single drug, as well as use of an echinocandin as monotherapy, may be problematic.
• Failure to recognize the significance of clinical isolates of Trichosporon may represent a medicolegal pitfall.
• Recognize that patients who survive trichosporonosis, particularly those with hepatosplenic involvement, may develop recurrent disease if the host immune system is suppressed again.
• 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

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3. Assaf RR, Weil ML. The superficial mycoses. Dermatol Clin. Jan 1996;14(1):57-67. [Medline].

4. [Best Evidence] [Guideline] Chagas-Neto TC, Chaves GM, Columbo AL. Update on genus Trichosporon. Mycopathologica. Sept 2008;166:121-132. [Medline]. [Full Text].

5. 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].

6. Madariaga MG, Tenorio A, Proia L. Trichosporon inkin peritonitis treated with caspofungin. J Clin Microbiol. Dec 2003;41(12):5827-9. [Medline].

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Keywords

infections, white piedra, trichosporonosis, neutropenia

Contributor Information and Disclosures

Author

Tyler E Warkentien, MD, Fellow, Department of Infectious Diseases, Naval Medical Center, San Diego
Tyler E Warkentien, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, Armed Forces Infectious Diseases Society, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Ryan C Maves, MD, Consulting Staff and Director, Bacteriology Program, United States Naval Medical Research Center Detachment, Lima, Peru
Ryan C Maves, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, Armed Forces Infectious Diseases Society, HIV Medicine Association of America, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

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
Braden R Hale, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Armed Forces Infectious Diseases Society, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

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
Jeffrey M Zaks, MD is a member of the following medical societies: American College of Cardiology, American College of Healthcare Executives, American College of Physician Executives, and American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
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
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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