Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients

Abstract

Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

Keywords: breakthrough infections; echinocandins; invasive fungal infections; liver transplantation; targeted antimycotic prophylaxis.

Figure 1

Perioperative risk factors for invasive fungal infections. Abbreviations: MELD: Model for End-Stage Liver Disease Score, ESRD: end-stage renal disease, PRBC: packed red blood cells, CMV: cytomegalovirus.

Figure 2

Flow chart of patient selection. Abbreviations: OLT: orthotopic liver transplantation; IFI: invasive fungal infection, b-IFI: breakthrough invasive fungal infection; EOS: end of study.

Figure 3

Kaplan–Meier curve: Mortality within 90 days depending on the cause of death. Abbreviations: OLT: orthotopic liver transplantation; IFI: invasive fungal infection.