Prophylaxis against Pneumocystis jirovecii pneumonia and toxoplasmosis with low-dose Trimethoprim-sulfamethoxazole (cotrimoxazole 20/100 mg) in heart transplant patients. The PAPTO-LOCO observational comparative study

Objectives Practice concerning post-transplant Pneumocystis prophylaxis remains heterogeneous. SXT benefits must be balanced with frequent toxicity. We aimed to assess whether a low-dose SXT strategy might limit toxicities while maintaining an undisrupted prophylaxis compared with a standard dose in a retrospective cohort of heart transplant population. Methods Patients undergoing heart transplant from two distinct centres, receiving daily SXT 20/100 mg versus daily SXT 80/400 mg between 2018 and 2020, were retrospectively included in the study. Demographic, immunosuppression and survival characteristics were collected to ensure group comparability. The occurrence of adverse effects and the rate of SXT discontinuation were compared between the two groups. Results Overall, 359 patients were recruited in the study, 108 patients for the standard-dose group and 251 patients for the low-dose group. The leading cause of prophylaxis discontinuation was cytopenia. We observed significantly more discontinuation in the standard-dose compared with the low-dose group (24.1% and 6.4%, respectively, P < 0.001). No patient with ongoing prophylaxis presented Pneumocystis pneumonia or toxoplasmosis during the 2-year follow-up. Two Pneumocystis infections in the low-dose group occurred during prophylaxis breaks. The rate of toxoplasmosis seroconversion was similar in both groups. Conclusions This retrospective study suggests that a low-dose SXT Pneumocystis prophylaxis strategy might offer a more favourable safety/efficacy profile than standard-dose prophylaxis after heart transplantation. These results should be confirmed in an interventional trial. Caution remains for toxoplasmosis serology D+/R- profiles.