Association of Infection Rate in Heart Transplant Recipients with Combined Tacrolimus and Sirolimus at High versus Low Concentration

Abstract

<h3>Purpose</h3> Assess the impact of tacrolimus-sirolimus (TAC/SRL) concentration on infection rate in heart transplant recipients (HTR). <h3>Methods</h3> A retrospective review of HTR on TAC/SRL for > 1 year from 01/2006-08/2019 was conducted. Drug concentrations were defined as high (≥ 15 ng/mL) or low (<15 ng/mL), calculated as the summation of individual medication's annual average concentration for every year of therapy. The primary outcome was median rate of infection per year, defined as positive culture or other documented clinical finding treated with a course of antimicrobial. Secondary outcomes included incidence of infection, biopsy-proven acute rejection (BPAR), clinically evident cellular rejection treated with high-dose corticosteroids, and reason for SRL initiation and discontinuation. <h3>Results</h3> A total of 22 patients were included, 9 vs. 13 in the high and low TAC/SRL groups, respectively. Baseline characteristics were similar between groups. HTR in the high TAC/SRL group had higher median infection rate per year of therapy compared to those in the low group (1.67 vs 0.75, p<0.001). Numerically there were more patients with any cellular rejection (Grade 0R, 1R, 2R or 3R) in the high (100%) compared to the low group (77%). There were no cases of antibody mediated rejection in either group. <h3>Conclusion</h3> Higher combined concentrations of TAC/SRL in HTR resulted in increased infections per year. Due to the retrospective nature of this study, it is difficult to conclude the association between high TAC/SRL level and rejection severity. Given the small sample size and retrospective design, additional studies are warranted to confirm infection rates and to prospectively assess the association of high combined TAC/SRL concentrations on allograft rejection.