Disseminated zygomycosis in a heart transplant recipient. Report of a rare case

Introduction: Cardiac transplantation is the „gold standard” in treatment of irreducible heart failure. Opportunistic infections lead to a high rate of mor-tality during first year after transplantation which de-clines to approximately 10-13% annually. Most causal pathogens involved are opportunistic or nosocomial; Cytomegalovirus, Aspergillus spp. and Pneumocys-tis jiroveci are frequently identified causative agents. Zygomycosis is an opportunistic infection, primarily associated with diabetes, neutropenia, hematologic malignancies and rare related to heart transplantation recipients. Zygomycetes fungi are ubiquitous in nature, occurring in decaying vegetables, foodstuffs, fruits and soil. Nosocomial infections can appear from sporangi-ospores disseminated of air-conditioning systems and wound dressings.
Case presentation: A 47 y.o. white male, with ortho-tropic heart transplantation (December 2016) for ir-reducible heart failure secondary to postviral dilated cardiomyopathy, with posttransplantation diabetes mellitus, had a stable status with immunosuppressive regimen (Tacrolimus 3 mg+Mycophenolate mofetil 2 g+Prednisone 10 mg/day). In January 2018 he un-derwent surgery for an uncomplicated inguinal hernia. Postoperative a prolonged bronchopneumonia develo-ped, not amendable to antibiotic regimens (Linezolid 600 mg i.v. b.i.d. + Imipenem/cilastatin 1 g i.v. o.d). Patient was admitted in March 2018 with cardiac fai-lure, prolonged febrile syndrome and multiple nodu-lar painless immobile tumors, located subcutaneously, randomly with inflammatory signs.
Fever, blood samples (leukocytosis with neutrophi-lia, elevated levels of ESR, fibrinogen, CRP) sustained an acute infectious episode. Repeated blood cultures were negative for presence of microorganisms inclu-ding fungus. Cardiac ultrasound did not confirm signs of cardiac damage. Histopathology obtained from sur-gical excision of nodules confirmed a necrotic granula-ted-suppurative inflammatory process. Whole body CT scan confirmed presence of multiple tumoral masses localized in brain, lungs, mediastinum. An opportu-nistic infection was suspected and a combination of anti-infectious agents was initiated. Despite sustained antifungal (Caspofungin 50 mg i.v. o.d.) and antivi-ral (Valacyclovir 500 mg orally b.i.d.) regimen among with supportive treatment for cardiac failure, blood transfusions, patient died at 14 days after admission. Histopathology performed after anatomopathological examination from brain, pulmonary, cardiac, gastroin-testinal, retroperitoneal specimens confirmed multiple septic secondary localizations. Microbiology examina-tions revealed the presence of Rhizopus azygosporus, a member of class Zygomycetes, order Mucorales, genus Rhizopus.
Conclusions: Early diagnostic of opportunistic in-fections remains a challenge in heart transplantation recipients. Aggressive fungal infections with mem-bers of Zygomycetes class is uncommon and must be considered in these patients, especially with atypical general and local manifestations. Mycological diagno-sis is challenging. A delay in diagnostic increase the mortality. Immunosuppressant chemotherapy required by recipients, especially in diabetic ones, will increase the incidence of emergent fungal infections. After our knowledge this is the first lethal case of Zygomycetes in-fection in a heart transplantation recipient reported in Romania.

ISSN
ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
INDEXING
The Romanian Journal of Cardiology is indexed by:
SCOPUS
EBSCO
ESC search engine
DOAJ
CNCSIS B+
CODE: 379
CME Credits: 10 (Romanian College of Physicians)
LICENSE