eMedicine Specialties > Infectious Diseases > Fungal Infections
Trichosporon Infections: Treatment & Medication
Updated: Nov 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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.
Adult
1.0-1.5 mg/kg/d IV qd
Pediatric
Administer as in adults
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
Documented hypersensitivity
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.
Adult
3-5 mg/kg/d IV over approximately 120 min
Pediatric
Administer as in adults
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
Documented hypersensitivity
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.
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
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)
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
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.
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
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)
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)
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.
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
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
Documented hypersensitivity
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.
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
Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine
Documented hypersensitivity
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.
Adult
70 mg IV once, followed by 50 mg IV q24h
Pediatric
Not established
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)
Documented hypersensitivity
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.
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
Increases sirolimus and nifedipine AUC approximately 20%
Documented hypersensitivity
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
More on Trichosporon Infections |
| Overview: Trichosporon Infections |
| Differential Diagnoses & Workup: Trichosporon Infections |
 Treatment & Medication: Trichosporon Infections |
| Follow-up: Trichosporon Infections |
| References |
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Further Reading
Keywords
infections, white piedra, trichosporonosis, neutropenia
