EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Geotrichum capitatum is a rare fungal pathogen that has infrequently affected immunocompromised patients with onco-hematologic diseases. Geotrichum capitatum invasive infection has been associated with poor prognosis, with a mortality rate ranging from 50% to 90%. Here, we report the first case of Geotrichum capitatum invasive fungal infection in a liver transplant recipient from an unrelated deceased donor, who was effectively treated with amphotericin B and voriconazole. We also reviewed the available literature in the field.

Key words : Blastoschizomyces capitatus, Invasive fungal infection, Magnusiomyces capitatus, Saprochaete capitate, Solid-organ transplantation

Invasive fungal infections (IFI) are a common cause of severe morbidity and even mortality in immunocompromised patients.¹ In the setting of liver transplant, IFIs usually occur in the perioperative phase. The most frequent IFIs are Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.² Geotrichum capitatum, which is also known as Blastoschizomyces capitatus (belonging to a class of saccharomycetes), has become an emerging cause of IFIs among onco-hematologic patients with severe neutropenia.³ This infection often occurs as a bloodstream infection with occasional secondary localizations, mainly in skin or lungs. Despite appropriate antifungal therapy, the mortality rate for patients with G. capitatum infection exceeds 50%.⁴

Here, we report the first case of G. capitatum-related invasive fungal infection in a liver transplant recipient. We also reviewed the available literature in this field.

A 52-year-old white man with hepatitis B-delta-related cirrhosis was admitted in July 2017 to our unit for hepatic encephalopathy and hydrothorax. At admission, the patient showed Child-Pugh and Model for End-Stage Liver disease scores of 10 and 22, respectively. During hospitalization, he developed hepatorenal syndrome, which required intensive care unit (ICU) admission. The patient underwent long-term empirical antibiotic therapy for sepsis of unknown origin (meropenem 1 g at 3 times per day and vancomycin 500 mg at 4 times per day). At 2 weeks after admission, the patient underwent liver transplant. He received a full graft from an unrelated deceased female donor (cause of death was cerebral hemorrhage) in accordance with the Italian allocation system. The patient’s early post-transplant course was complicated by pneumothorax and abdominal reintervention due to biliary leak. The immunosuppressive regimen was started with steroids and basiliximab and maintained with steroids and tacrolimus.

During the early post-transplant period, the patient received prophylactic therapy with ceftazidime, tigecycline, and anidulafungin. On day 7 post-transplant, bronchoalveolar lavage and blood samples, from the central venous catheter, were obtained. Samples were inoculated on blood agar BD, chocolate agar BD, and Sabouraud agar BD solid media and incubated for 24 hours at 37°C in anaerobiosis (VITEK MS MALDI-TOF, bioMérieux, Marcy-l'Étoile, France). Laboratory results revealed G. capitatum invasive infection.

After ruling out endophthalmitis and endocarditis, the patient started a treatment with liposomal amphotericin B at 5 mg/kg/day, adding within 5 days voriconazole (at 6 mg/kg twice daily as a loading dose and then at 4 mg/kg twice daily, adjusting the dose according to serum trough levels). Dual antifungal therapy was effective, with the patient showing clinical improvement and negative results in both blood cultures and bronchoalveolar lavage. However, he developed a further episode of Enterococcus faecium-related sepsis and subsequently died from multiorgan failure.

Geotrichum capitatum-related IFIs have rarely been reported to date.5 Neutropenia, previous or ongoing chemotherapy, and prolonged use of broad-spectrum antibiotics represent the most common risk factors in immunocompromised patients (Table 1). Conversely, both prolonged ICU stay and previous surgery are commonly described conditions among immunocompetent patients (Table 2).^6,7

To date, no specific treatment algorithm for G. capitatum-related IFIs has been established. Although the first introduced treatment was liposomal amphotericin B, recently published data have reported that voriconazole,⁵ posaconazole,^8,9 and isavuconazole¹⁰ monotherapy seemed to be equally effective.

Despite adequate antifungal treatment, outcomes of G. capitatum IFIs are generally poor. The mortality rate, ranging from 48% to 69%, reflects not only the suboptimal response to antifungal therapy but also the patient’s underlying comorbidities (Tables 1 and 2).

Invasive fungal infections can be a severe cause of morbidity and mortality in the early phase after solid-organ transplant. Due to significant changes in epidemiology, with increasing prevalence of non-albicans Candida strains, prophylactic strategies have been recently modified.^2,11 Since our patient displayed several risk factors for post-transplant IFI (including ICU admission before liver transplant, preoperative Candida colonization, acute renal failure with need for renal replacement therapy, reintervention, long-term broad-spectrum antibiotic use, pleural drainage, and mechanical ventilation),^4,12-14 he received prophylaxis with anidulafungin.¹¹ Unfortunately, this treatment was not effective. In fact, G. capitatum is considered intrinsically resistant to echinocandins, and these agents have been shown to be the cause of several episodes of breakthrough infections among neutropenic patients receiving echinocandins.¹⁵

Regarding antifungal therapy, our case confirmed the effectiveness of the combination of amphotericin B and voriconazole. However, we were not able to provide significant data about dosage due to the patient’s impaired renal function and potential drug-drug interactions.

Here, we report the first case of a G. capitatum IFI early after liver transplant, which was not effectively prevented by echinocandin prophylaxis but effectively treated with combined amphotericin B and azole therapy. Despite prophylaxis, high-risk liver transplant recipients should be actively screened for IFI development, and they should receive early tailored therapy to avoid graft dysfunction and multiorgan involvement.

Volume: 18 Issue: 6 November 2020

FULL TEXT