Summary to Emerging Fungal Infections In Solid Organ Transplant Recipients
1. Therapy with an agent that has proven activity against the fungus should be administered as early as possible.(Low, Strong)
2. Immunosuppression should be reduced when clinically feasible. To date, immune reconstitution inflammatory syndrome has not been described with emerging or rare fungal pathogens.(Low, Strong)
3. Surgical debridement of the affected areas should be performed whenever feasible and repeated as needed.(Low, Strong)
4. Antifungal therapy should be adjusted based on susceptibility testing at a reference laboratory. Although clinically validated antifungal susceptibility breakpoints are lacking, it is reasonable for therapy to be guided by general antifungal susceptibility patterns.(Low, Weak)
5. Clinicians should closely monitor for renal toxicity with AmB products. If using such agents, treatment should generally be with a lipid formulation of AmB (LF‐AmB; ie, liposomal or lipid complex formulations) as these have less toxicity.(Low, Strong)
6. Clinicians should closely monitor for Q‐T interval prolongation, drug interactions, hepatotoxicity, and neuropsychiatric side effects with azoles.(, )
7. Therapeutic drug monitoring of voriconazole should be considered to guide dose adjustments, especially in patients receiving higher doses or corticosteroids, although data for emerging fungal infections are lacking. Target voriconazole trough levels between 1.5‐4.5 mcg/mL are associated with the optimal balance of maximizing efficacy and minimizing toxicity. Based on very limited data in the prophylactic, setting the target posaconazole trough levels should be at least 0.7 mcg/mL. Routine monitoring of posaconazole levels may be unnecessary. We recommend checking serum trough levels when using the liquid formulation, in special populations (eg, patients with very high BMI, questionable drug absorption and those with cystic fibrosis) and when clinical response is suboptimal. It is unclear whether therapeutic drug levels are useful for isavuconazole.(, )
8. Adjuvant therapy with interferon‐gamma and/or granulocyte-macrophage colony stimulating factor may be considered with caution in cases refractory to standard antifungal therapy.(Very Low, Weak)
Posaconazole may be considered for maintenance therapy once clinical stability has been achieved.(Low, Weak)
Isavuconazole is a reasonable second‐line option for mucormycosis.(Moderate, Weak)
TABLE 2: Recommended treatment of emerging and rare fungal infections in solid organ transplant recipients
|Mucormycetes||Surgical excision/debridement is recommended for all infections outside of lungs
|Fusarium||Surgical excision or debridement is recommended whenever feasible
|Scedosporium||Surgical excision or debridement is recommended whenever feasible
|Lomentospora prolificans||Surgical debridement should be considered primary therapy (resistant to virtually all of the available antifungal agents)
|Purpureocillium||Surgical excision or debridement is recommended whenever feasible and may be sufficient for isolated cutaneous disease
|Trichoderma||Surgical excision or debridement is recommended whenever feasible
|Surgical excision or debridement is recommended whenever feasible
o Caspofungin + voriconazole or posaconazole
|Acremonium||Surgical excision or debridement is recommended|
|Surgical excision or debridement is recommended whenever feasible and may be sufficient for isolated cutaneous disease
Standard antifungal dosing is recommended: LF‐AmB 5 mg/kg daily; AmBd 1‐1.5 mg/kg daily; voriconazole 6 mg/kg intravenous q 12 h × 2 loading doses followed by 4 mg/kg intravenous or 200-300 mg orally twice daily; itraconazole 200 mg twice daily; posaconazole delayed release tablets 300 mg daily; caspofungin 70 mg loading dose followed by 50 mg daily; micafungin 100 mg daily; anidulafungin 200 mg loading dose followed by 100 mg daily; isavuconazonium sulfate 372 mg intravenous or oral q 8 h for six doses followed by 372 mg daily).
AmBd, amphotericin B deoxycholate; LF‐AmB, lipid formulation of amphotericin B.
a Isavuconazonium sulfate is FDA‐approved for Mucorales infections.
b Voriconazole is FDA‐approved for Scedosporium apiospermum and Fusarium infections when intolerant or refractory to other agents.
c Amphotericin B deoxycholate is FDA‐approved for Sporothrix infections.
d Terbinafine has some in vitro synergy but the agent is keratinophilic and does not penetrate well into other tissues hence limiting efficacy for invasive disease.
PREVENTION AND PROPHYLAXIS
The most common mechanism for colonization or infection is via environmental exposure. Patients should be instructed to avoid visiting construction sites and poultry farms, manipulating air‐conditioning filters, and contact with sewage or decaying material. To reduce the risk of invasive fungal infection due to transmission during the transplantation process, care should be taken in accepting organs from near drowning victims. Organ procurement agencies should report all fungal isolates from a donor to the recipient center. Not all patient with fungal colonization require prophylaxis. Certain colonizing fungi are very rarely pathogenic (eg, Cladosporium¸ Purpureocillium, and Penicillium species) and their presence generally does not require prophylaxis. By contrast, the mucormycetes and Scedosporium have been associated with disseminated infection in highly immunocompromised patients. Prophylaxis may be considered in such patients and in recipients of donor lungs that are colonized with these fungi.(Very Low, Weak)
Emerging Fungal Infections In Solid Organ Transplant Recipients
April 1, 2019
External Publication Status
Country of Publication
These updated AST‐IDCOP guidelines review the epidemiology, diagnosis, and management of emerging fungi after organ transplantation.
Target Patient Population
Solid organ transplant patients
Female, Male, Adolescent, Adult, Older adult
Health Care Settings
Ambulatory, Hospital, Operating and recovery room, Outpatient
Nurse, nurse practitioner, physician, physician assistant
Diagnosis, Management, Treatment
D014180 - Transplantation, D019737 - Transplants, D000935 - Antifungal Agents, D016377 - Organ Transplantation, D000908 - Antibodies, Fungal, D000072742 - Invasive Fungal Infections
prophylaxis, antimicrobial prophylaxis, antifungal, solid organ transplant
Shoham, S, Dominguez, EA; on behalf of the AST Infectious Diseases Community of Practice. Emerging fungal infections in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019; 33:e13525.