Premature Discontinuation of Trimethoprim/Sulfamethoxazole Prophylaxis in Abdominal Transplant Recipients: A Deeper Dive.

Abstract

Trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis can prevent Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections (OI). We sought to assess the frequency, causative factors, and impact of early TMP/SMX discontinuation in abdominal solid organ transplant (SOT). This is a single-center, retrospective cohort study of abdominal SOT recipients at Mayo Clinic Arizona (MCA) between January 2021 and June 2023. Primary study goals were to determine the rate and reasons behind early TMP/SMX discontinuation and whether TMP/SMX prophylaxis was reinitiated. Secondary outcomes included mean duration of therapy, alternative prophylactic agent utilized, and incidence of TMP/SMX-preventable OI. A total of 930 abdominal SOT recipients were included (592 kidney, 253 liver, 85 multiorgan transplants). TMP/SMX was discontinued early in 184 (20%) patients: 77 kidney, 84 liver, 23 multiorgan. Predominant reasons for discontinuation were hyperkalemia (39%) and cytopenias (35%). Median duration of TMP/SMX prophylaxis before discontinuation was 54.5 (18.0, 93.2) days. TMP/SMX was not resumed in 62% of cases (36% kidney, 89% liver, 52% multi-organ). The predominant reason for non-resumption was alternative prophylaxis with no clear intent to rechallenge TMP/SMX (70%). Alternative prophylaxis included pentamidine (43%), none (30%), dapsone (22%), and atovaquone (5%). Of patients reinitiated, 86% (59/69) successfully remained on TMP/SMX through the prophylaxis period. One TMP-SMX-preventable OI (nocardiosis) was observed in the TMP/SMX discontinuation group. TMP/SMX is often discontinued prematurely in SOT recipients without resumption despite resolution of the offending cause. TMP/SMX prophylaxis should be maintained where possible, as alternative therapy may not offer the same broad spectrum of protection against OI.