Effectiveness and safety of isavuconazole treatment for invasive fungal infections in solid organ transplant recipients

Author:

Arnau Monforte, Ibai Los-Arcos, Maite Martin, David Campany, Victor Monforte, Cristina Berastegui, Judith Sacanell, Lluis Castells, Isabel Campos-Varela, Ricardo Ferrer, Carles Bravo, Joan Gavaldà, Oscar Len

Author address:

Hospital Universitari Vall d’Hebron, Barcelona, Spain

Full conference title:

European Congress of Clinical Microbiology and Infectious Diseases 2020

Date: 2 July 2020

Abstract:

Abstract third-party references: Supported by a grant from Pfizer

Background: IFI is a significant complication following solid organ transplantation. Voriconazole is the treatment of choice for invasive aspergillosis. However, it is associated with many serious adverse events and has an important interaction with anticalcineurin and mTOR inhibitors. Isavuconazole is an alternative for voriconazole in hematological patients affected with IFI. Evidence regarding its use in SOTR is lacking. Our aim was to study the safety and tolerability of isavuconazole in SOTR.

Materials/methods: We prospectively included all SOTR from January 2018 to November 2019 who received isavuconazole for treatment of an IFI. The study was performed in Vall d’Hebron University Hospital, Barcelona, Spain. The duration of treatment depended on the type of infection and the treating physician. All patients were followed at least for 3 months after treatment. IFI was defined by ISHLT criteria for lung transplant recipients (LTR) or revised EORTC/MSG criteria in non-LTR.

Results: We included 28 SOTR treated with isavuconazole. Most of them (26/28, 92.9%) were LTR. The most frequent IFI treated was tracheobronchitis (12/28, 42.9%). SOTR were infected with Aspergillus spp. (87.5%): A. terreus (7/28, 25%) and A. fumigatus (7/28, 25%); all of them with ISA MIC≤0.5 μg/mL. Other treated infections included Scedosporium prolificans, Alternaria alternata and Trichosporon ashaii, one case each. ISA was the initial treatment in 15/28 (53.6%) SOTR and following voriconazole due to adverse events in 4/28 (14.3%).The median duration of treatment was 98 days (IQR 19-193). Hepatotoxicity (mild elevation of cholestatic enzymes) was the commonest adverse event (39.3%). Myopathy was reported in 5/28 (17.9%) SOTR related to combination with corticosteroids. None of the patients developed breakthrough IFI. ISA was prematurely discontinued in only one patient (3.7%) due to significant elevation of transaminases. Dose of anticalcineurin inhibitors was initially adjusted in 33% SOTR, and up to 66.7% on the first days of treatment with a median of 33% decrease (1.2 mg). Four patients received concomitantly mTOR inhibitors with overall good tolerance. Eight (28.5%) SOTR died while on isavuconazole treatment. Another patient died during follow-up.

Conclusions: We consider that ISA was well tolerated and proved to be an effective treatment for IFI in SOTR.

Presenter email address: amonforte92@gmail.com

Abstract Number: 8095

Link to conference website:

Link Conference abstract: 

ECCMID 2020

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