Invasive Aspergillosis In Solid‐Organ Transplant Recipients

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

Recommendations

DIAGNOSTIC STRATEGIES

Serum GM is not recommended to diagnose IA in SOT recipients. (Moderate, Strong)
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BAL GM is the preferred sampling method for the diagnosis of IPA in SOT recipients. (High, Strong)
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BAL GM index value cutoff of ≥1.0 is preferred for the diagnosis of IA in lung and non‐lung transplant recipients, in combination with other fungal diagnostic modalities (eg, chest CT scan, culture). (Moderate, Strong)
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Standardized BAL Aspergillus PCR can be used in combination with other fungal diagnostic modalities (eg, chest CT scan, BAL GM, culture) for the diagnosis of IA. (Low, Strong)
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Serum or BAL β‐D‐Glucan is not recommended for early screening and diagnosis of IA in lung and liver transplant recipients. (Low, Strong)
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TREATMENT

Early initiation of antifungal therapy in patients with strongly suspected IA is warranted while a diagnostic evaluation is conducted. (High, Strong)
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Voriconazole is the drug of choice to treat all forms of IA. (High, Strong)
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Isavuconazole and lipid formulations of AmB, preferably L‐AmB, can be considered as alternative agents. (Moderate, Strong)
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Posaconazole can be considered for salvage therapy in patients who fail or do not tolerate first‐line antifungals. (Low, Strong)
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Primary therapy with an echinocandin is not recommended. (Low, Strong)
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However, echinocandins can be considered when other antifungals are contraindicated. (Low, Weak)
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Combination therapy can be considered in select cases such as in patients with disseminated or CNS disease. (Low, Weak)
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Inhaled AmB (in conjunction with systemic antifungal therapy) may be used in the setting of tracheobronchial aspergillosis associated with anastomotic endobronchial ischemia, or ischemic reperfusion injury due to airway ischemia associated with lung transplant. (Low, Weak)
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Duration of treatment should be guided by clinical and radiological response; most cases will require a minimum of 12 weeks, if tolerated. (Moderate, Strong)
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Secondary prophylaxis should be considered in patients with history of IA who undergo augmentation of immunosuppression (eg, T‐cell depletion, high‐dose steroids) and during episodes of prolonged neutropenia (eg, <500 cells/μL longer than 7 days). (Low, Weak)
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Routine antifungal susceptibility is not recommended, but it can be considered for patients suspected to have an azole‐resistant isolate and those who are unresponsive to antifungal agents. (Low, Weak)
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Antifungal TDM is recommended for all patients receiving voriconazole‐based therapy for IA. (Moderate, Strong)
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Dosing of antifungals should be adjusted in coordination with a transplant pharmacist in special populations including pediatrics, CF, and ECMO/critically ill patients. (Low, Strong)
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Dose of CNI/mTOR inhibitor should be reduced (and increased) in coordination with the respective organ transplant subspecialist and a transplant pharmacist in patients starting (and completing), triazole therapy, respectively; and CNI/mTOR inhibitor levels monitored closely. (Moderate, Strong)
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Baseline and follow‐up electrocardiogram to assess QT interval (for patients receiving triazoles other than isavuconazole) and regular skin examination (for patients receiving voriconazole) are indicated in patients receiving chronic azole therapy. (High, Strong)
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Surgery and reduction of immunosuppression are important adjunctive components of management in selected patients. (Low, Strong)
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Colony‐stimulating factors may be considered in neutropenic patients with IA. (Low, Strong)
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PREVENTION

Targeted prophylaxis in patients with any of the following high‐ risk factors is recommended:
  • Re‐transplantation (second or third liver transplant).
  • Renal replacement therapy (hemodialysis or continu‐ ous venovenous dialysis) at the time of or within 7 days of transplantation.
  • Reoperation involving thoracic or intra‐abdominal cavity, for example, exploratory laparotomy or any intrathoracic surgery.
(Moderate, Strong)
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Anidulafungin, micafungin or caspofungin in standard dose, or voriconazole is recommended for the use of targeted prophylaxis against IA in liver transplant recipients. (High, Strong)
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Targeted prophylaxis with a lipid formulation of amphotericin B in dosages ranging 3‐5 mg/kg may be considered. (Moderate, Weak)
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Targeted prophylaxis should be continued for 14‐21 days. (High, Strong)
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Screening with serum GM and β‐D‐Glucan is not recommended for preemptive therapy. (Low, Weak)
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Lung transplant recipients

These recommendations are intended for the first year following the lung transplant. No definite recommendation can be made for the later years following lung transplantation due to the lack of published data.
Either universal prophylaxis or preemptive therapy can be employed as a strategy to prevent IA in lung transplant recipients, depending on the availability of the diagnostic tests. (Moderate, Strong)
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In cases where a preemptive therapy strategy is employed, both BAL culture and BAL GM should be incorporated into the protocol. (Low, Strong)
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A BAL GM index value of 1.0 is preferred as a threshold for the initiation of preemptive therapy. (Low, Strong)
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It is recommended to initiate targeted antifungal prophylaxis if any one of the following risk factors is present in lung transplant recipients:
  • Pre‐transplant Aspergillus colonization
  • Post‐transplant Aspergillus colonization within a year of transplant
  • Single‐lung transplant
  • Positive intraoperative Aspergillus culture in CF patient.
(Moderate, Strong)
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Targeted antifungal prophylaxis against IA may be considered if more than one of these risk factors are present in lung transplant recipients:
  • Early airway ischemia
  • Induction with alemtuzumab or anti‐thymocyte globulin
  • Cytomegalovirus infection
  • Rejection and augmented immunosuppression (particularly the use of T cell‐depleting monoclonal antibodies post‐transplant)
  • Acquired hypogammaglobulinemia (IgG level <400 mg/dL).
(Low, Weak)
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The use of serum GM for the screening of IA is not recommended in lung transplant recipients. (Moderate, Strong)
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In cases of universal and targeted antifungal prophylaxis, the recommended duration is 4‐6 months. However, when using a preemptive strategy, the duration of antifungal therapy should be 3‐4 months. (Moderate, Strong)
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With regard to the choice of the drugs against Aspergillus in lung transplant recipients, the following recommendations are made:
No data exist regarding the use of inhaled amphotericin (lipid or deoxycholate) in preemptive therapy (ie, positive Aspergillus culture or positive BAL GM), and they should be used with caution in this setting. (Low, Strong)
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Inhaled amphotericin B or lipid preparation of amphotericin B can be used for targeted prophylaxis post‐operatively in patients with a risk of developing IA. Caution should be exercised in single‐lung transplant recipients. The dosage of D‐AmB may vary from 20 mg three times a day to 25 mg/d. The duration of prophylaxis should be guided by interval airway inspection, respiratory surveillance fungal cultures, and clinical risk factors. (Low, Weak)
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Nebulized ABLC can be used at a dose of 50 mg once every two days for two weeks, and then once per week for at least 13 weeks. (Low, Weak)
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Nebulized L‐AmB can be administered as 25 mg three times/week for two months, followed by weekly administration for 6 months, and twice per month thereafter. (Low, Weak)
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Systemic antifungal agents active against Aspergillus such as voriconazole (6 mg/kg for two doses followed by 4 mg every 12 h), itraconazole (200 mg every 12 h), or posaconazole (300 mg/d delayed‐release tablets) can be used for prophylaxis or preemptive therapy. (, )
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Liver enzymes should be monitored to assess the hepatic toxicity in patients receiving systemic antifungal prophylaxis with azoles. (Moderate, Strong)
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Voriconazole should be used with caution in patients with previous history of squamous cell carcinoma, or who are residing in geographical areas with higher incidence of cutaneous malignancy. Voriconazole use warrants photo‐protective measures to be put in place, and enhanced skin surveillance. (High, Strong)
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Alternatives to voriconazole may include posaconazole or isavuconazole. (Low, Weak)
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Heart Transplant Recipients

Targeted prophylaxis with itraconazole or voriconazole at a dosage of 4 mg/kg every twice daily for 50‐150 days, or echinocandins up to 120 days, is recommended in recipients with one or more of the following risk factors:
  • Isolation of Aspergillus species in respiratory tract cultures without radiological abnormality
  • Presence of airborne Aspergillus spores in the ICU
  • Re‐operation (thoracic)
  • Presence of CMV disease
  • Post‐transplant hemodialysis
  • Existence of an episode of IA in any patient within the heart transplant program, 2 months before or after heart transplant.
(Low, Strong)
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Recommendation Grading

Overview

Title

Invasive Aspergillosis In Solid‐Organ Transplant Recipients

Authoring Organization

American Society of Transplantation

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 AST‐IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. 

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)

D019737 - Transplants, D016377 - Organ Transplantation, D001228 - Aspergillosis, D055732 - Pulmonary Aspergillosis

Keywords

aspergillosis, infection prevention, infection, solid organ transplant, mold

Source Citation

Husain, S, Camargo, JF, on behalf of the AST Infectious Diseases Community of Practice. Invasive Aspergillosis in solid‐organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13544.