Endemic Fungal Infections In Solid Organ Transplant Recipients

Publication Date: April 1, 2019
Last Updated: March 14, 2022

Recommendations

BLASTOMYCOSIS

Diagnostic strategies

Growth of B. dermatitidis from clinical specimens and/or direct visualization of morphologically consistent yeast forms in sputum, BAL fluid, and tissue specimens establishes the diagnosis. (Moderate, Strong)
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The Blastomyces antigen EIA, performed on serum, urine, BAL fluid, and CSF, provides a non‐invasive diagnostic tool for rapid diagnosis and monitoring treatment response. (Low, Strong)
However, its utility is limited by variable sensitivity (62%‐83%) and high cross‐reactivity with other endemic fungi.
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Serologic Blastomyces antibody assays and the (1‐3)‐β‐D‐glucan assay are not diagnostically useful. (Moderate, Strong)
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Treatment

Azole monotherapy may be considered for mild, localized infections. Itraconazole (200 mg twice daily) remains first line. (Moderate, Strong)
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For moderate, severe, and/or disseminated infection, initial therapy with lipid formulation amphotericin is recommended for a minimum of 1‐2 weeks or until clinical improvement is demonstrated, followed by step‐down azole therapy to complete 12 months of therapy. (Moderate, Strong)
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The preferred treatment of CNS blastomycosis is lipid formulation amphotericin for 4‐6 weeks, followed by voriconazole (200‐400 mg twice daily) for at least 12 months. Alternative stepdown therapy with fluconazole 800 mg daily is recommended in the setting of voriconazole intolerance. (Moderate, Strong)
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Therapeutic monitoring of azole serum drug levels is highly recommended during therapy. (Moderate, Strong)
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Limited data suggest that serial urine Blastomyces antigen EIA monitoring may be useful to follow response to therapy. Suppressive therapy following successful treatment may be considered. (Low, Weak)
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Prevention

Symptom assessment and chest radiography are the recommended screening for transplant candidates with potential Blastomyces exposure. (Low, Strong)
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Primary antifungal prophylaxis for blastomycosis after transplant is not recommended, but transplant recipients should avoid at‐risk environmental exposures. (Low, Strong)
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COCCIDIOIDOMYCOSIS

Diagnostic strategies

Growth of Coccidioides sp. from clinical specimens and/or direct visualization of the characteristic spherule containing endospores are confirmatory of the diagnosis. (Moderate, Strong)
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Among the three available Coccidioides serologic assays (EIA, ID, and CF), the EIA is recommended for initial screening. CF, though positive later in infection, is quantitative and provides prognostic information regarding severity and resolution of infection. (Moderate, Strong)
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Molecular diagnostic techniques are increasing in availability. Coccidioides PCR testing of respiratory and CSF specimens demonstrate high sensitivity and specificity. (Low, Strong)
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Multiple test modalities may be needed for diagnosis, with repeat studies over time to increase the likelihood of assay positivity in the setting of clinical infection. (Moderate, Strong)
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Treatment

Azole monotherapy is recommended for clinically stable individuals with acute or chronic pulmonary coccidioidomycosis. Fluconazole (400 mg once daily) remains first line. (Low, Strong)
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For severe and/or rapidly progressing acute pulmonary or disseminated coccidioidomycosis, amphotericin (lipid formulation amphotericin is preferred) is recommended until the patient has stabilized, followed by fluconazole. (Low, Strong)
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Fluconazole, 400‐1200 mg daily, is recommended as initial therapy for meningeal coccidioidomycosis. (Moderate, Strong)
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Recommended treatment duration for coccidioidomycosis in 6‐12 months, but this should be individualized based on response. (Low, Strong)
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Due to the high risk of relapse or reactivation infection following the treatment course, solid organ transplant recipients with all forms of coccidioidomycosis should receive lifelong azole suppression. (Very Low, Strong)
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Prevention

All transplant candidates should be assessed for travel to or residence in a Coccidioides endemic region. If deemed at risk, an additional evaluation for active coccidioidomycosis should be untaken with a symptom assessment, chest X‐ray, and serologic testing. (Low, Strong)
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All transplant recipients in endemic areas, without active coccidioidomycosis and regardless of serostatus, should receive oral azole prophylaxis for a minimum of 6‐12 months post‐transplant. (Low, Strong)
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Transplant recipients who receive allografts from donors with prior or active Coccidioides infection should receive preemptive azole therapy to prevent or mitigate infection. Lifelong azole therapy (fluconazole 400 mg daily) is recommended for lung recipients. Nonlung recipients should receive 6‐12 months of preemptive azole therapy (fluconazole 400 mg daily), followed by the option of lifelong step‐down therapy (fluconazole 200 mg daily) or azole discontinuation with clinical and serologic monitoring for coccidioidomycosis. (Low, Strong)
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HISTOPLASMOSIS

Diagnostic strategies

Growth of H. capsulatum from clinical specimens is the definitive diagnostic test, but culture make take up to 4 weeks to demonstrate growth. (Moderate, Strong)
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Direct visualization of morphologically consistent yeast forms in blood, bone marrow, BAL, CSF, and/or other tissue specimens can expedite the diagnosis. (Moderate, Strong)
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The Histoplasma antigen EIA should be performed on serum and urine if histoplasmosis is suspected as this assay provides a rapid, non‐invasive method for diagnosis. Histoplasma antigen EIA can also be performed on BAL fluid and CSF as clinically indicated. Sensitivity is improved with combined testing from multiple sources and in the setting of disseminated infection. (Moderate, Strong)
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Histoplasma antibody testing is of limited utility in solid organ transplant recipients due to poor sensitivity. (Moderate, Strong)
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Treatment

Recommended treatment for mild to moderate histoplasmosis is itraconazole, 200 mg twice daily for at least 12 months. (Moderate, Strong)
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For moderately severe and severe histoplasmosis, amphotericin (lipid formulation preferred) is recommended for 1‐2 weeks or until there is stabilization of the infection, followed by step‐down therapy with itraconazole (200 mg twice daily) to complete a 12‐ month total treatment course. (High, Strong)
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For individuals refractory or intolerant of first‐line agents, the newer generation azoles (voriconazole, posaconazole, and isavuconazole) should be used for treatment in preference to fluconazole. (Low, Strong)
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Concomitant reduction of immunosuppression, especially the calcineurin inhibitor regimen, is recommended to lessen the risk of relapse. (Low, Strong)
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Urine and serum Histoplasma antigen EIA levels typically fall with effective treatment and can be used to follow treatment response and assess for relapse. Relapse is more likely to occur if the urine Histoplasma antigen level is >2 ng/mL at the time of stopping therapy. (Low, Strong)
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Prevention

Screening for prior histoplasmosis in endemic areas is not recommended prior to organ transplant. (Moderate, Strong)
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Primary prophylaxis for histoplasmosis in the post‐transplant setting is not recommended. However, transplant recipients should be counseled to avoid at‐risk exposures. (Low, Strong)
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Individuals who have recovered from active histoplasmosis during the 2 years before the initiation of immunosuppression may be considered for azole prophylaxis, typically with itraconazole 200 mg daily. (Low, Weak)
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Serial monitoring of Histoplasma antigen EIA levels should be performed in solid organ transplant recipients with previous histoplasmosis and during periods of intensive immunosuppression to assess for relapse. (Low, Weak)
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Recommendation Grading

Disclaimer

Overview

Title

Endemic Fungal Infections In Solid Organ Transplant Recipients

Authoring Organization

Publication Month/Year

April 1, 2019

Last Updated Month/Year

December 2, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre‐ and post‐transplant period. 

Target Patient Population

Solid organ transplant patients

Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Operating and recovery room, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D014180 - Transplantation, D019737 - Transplants, D016377 - Organ Transplantation, D000072742 - Invasive Fungal Infections, D003047 - Coccidioidomycosis, D006660 - Histoplasmosis, D001759 - Blastomycosis

Keywords

fungal infection, blastomycosis, coccidioidomycosis, histoplasmosis, azoles, solid organ transplant

Source Citation

Miller, R, Assi, M; on behalf of the AST Infectious Diseases Community of Practice. Endemic fungal infections in solid organ transplant recipients—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13553.