Impact of Targeted Posaconazole Prophylaxis in Heart Transplant Recipients During an Outbreak of Early Invasive Aspergillosis

Background

There are no established recommendations for systematic or targeted antifungal prophylaxis in heart transplant recipients (HTRs), resulting in heterogeneous practices. An outbreak of post-surgical invasive aspergillosis (IA) among HTR, which coincided with construction activities near our heart transplant unit, prompted the initiation of primary posaconazole (POS) prophylaxis in patients at highest risk.

Methods

This single-center retrospective descriptive study was conducted from March 2020 to May 2022 and describes the use of POS primary prophylaxis in high-risk HTR. The following risk factors were considered as indications for initiating prophylaxis: re-operation, post-transplantation hemodialysis, post-surgical extracorporeal membrane oxygenation (ECMO), re-transplantation, prolonged post-transplant mechanical ventilation (i.e., >72 h), cytomegalovirus (CMV) infection within the first month post-transplant, and a positive pre-transplant Aspergillus serology. The duration of prophylaxis was individualized, with treatment initiating in response to the risk factor and continuing for a median of 28 days after its resolution.

Results

POS prophylaxis was administered in 12 of 33 HTR (36.4%). The most common risk factors encountered were prolonged mechanical ventilation (>72 h, 91.6%) and CMV infection (58.3%). Most patients (91.6%) had at least two risk factors for IA, and more than half (58.3%) had three or more. Notably, no cases of IA were observed during the study period. Some patients experienced liver function abnormalities and drug–drug interactions.

Conclusion

Targeted POS prophylaxis may be an option for high-risk HTR during an outbreak. Close monitoring of liver function, POS levels, and tacrolimus concentrations is recommended.