BACKGROUND: Despite limited data supporting use in solid organ transplant (SOT) recipients, atovaquone and dapsone are often used as alternatives to trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PJP) prophylaxis. METHODS: This single-center, retrospective cohort study describes a multi-organ program's experience with alternative PJP prophylaxis. Adult SOT recipients transplanted November 13, 2020 to November 13, 2022 who received non-TMP-SMX PJP prophylaxis and had >
1 year follow-up were included. RESULTS: Among 953 SOTs performed, 333 (34.9%) recipients received alternative PJP prophylaxis (319 [95.8%] atovaquone and 14 [4.2%] dapsone). Alternative prophylaxis was initiated in 76 (22.8%) recipients without starting TMP-SMX, mostly due to sulfa allergy (62, 81.6%). In 257 recipients who started TMP-SMX, common reasons for switching to alternatives were hyperkalemia (105, 40.9%) and leukopenia (77, 30.0%). While 79.8% of recipients had these adverse effects resolve, only 27.3% resumed TMP-SMX. Tolerance was high after resumption (85.7%). Barriers to accessing alternative prophylaxis included cost (25, 7.5%) and prior authorizations (26, 7.8%). There was one case of severe disseminated toxoplasmosis, one case of Nocardia infection, and no cases of PJP. CONCLUSION: Alternative PJP prophylaxis carries risk of breakthrough infection and barriers to initiation. Since most recovered from adverse effects of TMP-SMX and tolerated resumption, providers should re-trial TMP-SMX when feasible.