Early vs Late Enteral Trimethoprim-Sulfamethoxazole in Critically Ill Patients With Pneumocystis

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice for Pneumocystis Jirovecii Pneumonia (PCP). In critically ill patients, intravenous (IV) administration is often preferred due to concerns about enteral absorption or access. However, the IV formulation necessitates large volumes of diluent to avoid crystallization, potentially contributing to fluid overload. This study evaluates whether early enteral conversion of TMP-SMX is associated with differences in mortality or fluid balance among critically ill patients with PCP.


Methods: Retrospective cohort study of adult ICU patients treated with TMP-SMX for PCP. Patients were stratified into early versus late enteral conversion groups. Early conversion was defined as initiation of enteral therapy within 48 hours of treatment or maintenance on enteral TMP-SMX for at least the first 48 hours. Patients who died or were discharged within 48 hours were excluded. Multivariable Cox proportional hazards regression was used to assess the impact of early enteral conversion on the primary outcome of 90-day mortality. The secondary outcome was mean daily fluid balance on treatment days 2-6.


Results: 183 patients met inclusion criteria with 108 that underwent early enteral conversion, while 75 underwent late conversion. Baseline severity of illness, including oxygen status, APACHE IV and SOFA scores, and need for dialysis, was comparable between groups. 90-day mortality was 50.9% in the early conversion group compared to 61.3% in the late conversion group. After adjusting for age, severity scores, and need for mechanical ventilation or ECMO, early conversion was not associated with increased 90-day mortality (HR 0.74, 95% CI 0.50 - 1.11). Patients in the early conversion group had trended towards lower mean daily fluid balance during treatment days 2-6 (-0.443 L vs -0.127 L, p=0.05).


Conclusions: Among critically ill patients with PCP, early conversion to enteral TMP-SMX was not associated with increased mortality and may decrease cumulative fluid balance. These findings support the safety and potential physiologic benefit of early enteral administration of TMP-SMX in ICU patients.