Non- Aspergillus invasive mould infections in liver transplant recipients : a French national retrospective case-control study, 2007 to 2021

Abstract Background Non-Aspergillus invasive mould infections (IMIs) are emerging in immunocompromised patients and liver is the second most commonly organ transplanted worldwide. Methods We conducted a multicenter retrospective case-control (1:1) study of liver transplant recipients diagnosed with non-Aspergillus IMIs in France between January 2007 and December 2021. Results We identified 27/14,332 (0.18%) LT recipients with non-Aspergillus IMIs. Mucorales spp. (48%) were the most common pathogens, followed by Scedosporium spp. (14%), Fusarium spp. (14%), and other IMIs (25%). Lungs were the primary infection site, followed by soft tissues, abdomen, brain, sinuses, heart, and bone. Multivariate analysis showed that a MELD score > 20 prior to transplantation and primary antifungal prophylaxis (with echinocandins or fluconazole) tended to increase the risk of non-Aspergillus IMIs by nearly threefold ((aOR: 3.73, 95% CI [0.90-15.45], p = 0.07) and (aOR: 3.93; 95% CI [0.94-16.42], p = 0.06) respectively). The 6-month mortality rate was 55%. In a Cox survival model, non-Aspergillus IMIs were associated with a threefold increase in mortality risk ((HR: 3.82 [2.01-7.26] p<0.001). Conclusion Non-Aspergillus IMIs are rare but highly fatal infections whose early diagnosis in high-risk liver-transplanted patients is essential. Whether or not recently available molecular tools for diagnosing non-Aspergillus IMIs will improve their prognosis in the liver transplantation setting remains to be studied.