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Meta-Analysis
. 2021 Nov;64(11):1317-1327.
doi: 10.1111/myc.13362. Epub 2021 Aug 23.

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis

Milo Gatti  1   2 , Matteo Rinaldi  3 , Giuseppe Ferraro  3 , Alice Toschi  3 , Natascia Caroccia  3 , Federica Arbizzani  3 , Emanuel Raschi  1 , Elisabetta Poluzzi  1 , Federico Pea  1   2 , Pierluigi Viale  1   3 , Maddalena Giannella  1   3
Affiliations
Meta-Analysis

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis

Milo Gatti et al. Mycoses. 2021 Nov.

Abstract

Introduction: Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthrough-invasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals.

Materials and methods: Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP).

Results: 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24-2.99) and observational studies (OR 1.43, 95% CI 0.28-7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97-24.03) was noted.

Conclusions: Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted.

Keywords: antifungal prophylaxis; breakthrough-invasive fungal infection; echinocandins; liver transplant recipients.

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Conflict of interest statement

FP participated in speaker bureau for Angelini, Basilea Pharmaceutica, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Pfzer and Sanof Aventis, and in advisory board for Angelini, Basilea Pharmaceutica, Correvio, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Novartis, Pfzer, Shionogi and Thermo‐Fisher. Other authors have none to declare.

Figures

FIGURE 1
FIGURE 1
PRISMA flow diagram for study selection
FIGURE 2
FIGURE 2
Forest plot of breakthrough IFI among OLT recipients receiving antifungal prophylaxis with echinocandins compared to other agents in randomised controlled trials
FIGURE 3
FIGURE 3
Forest plot of breakthrough IFI among OLT recipients receiving antifungal prophylaxis with echinocandins compared to other agents in observational studies
See this image and copyright information in PMC

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