Optimizing Pneumocystis jirovecii Prophylaxis in Immunocompromised Patients: Defining the Clinical Role of Atovaquone

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is associated with poor outcomes in immunocompromised patients. Cotrimoxazole is the first-line prophylactic agent, with atovaquone an alternative. At our center, atovaquone use considerably increased after 2020. The aims of this retrospective cohort study were to understand the usage of atovaquone over time and explore the reasons for this increase. METHODS: Patients receiving atovaquone for PJP prophylaxis from 2015 to 2022 were included. Clinical data were extracted to characterize atovaquone prescribing patterns and cotrimoxazole contraindications, with comparisons made between patients before 2020 and those afterward. RESULTS: Here, 149 patients were included, 24 (16%) before 2020 and 125 (84%) after 2020. The cohort comprised solid organ transplant recipients (49%), patients with hematologic conditions (35%), and human immunodeficiency virus (5%). Reasons for not prescribing cotrimoxazole included cytopenias (37%), renal impairment (15%), and drug interactions (12%). Median duration was significantly longer after 2020 (6.0 vs. 2.3 months, p = 0.047). Before 2020, most patients (71%) had underlying hematologic disease, but after 2020, solid organ transplant recipients accounted for 60%. Renal impairment appeared as a contraindication to cotrimoxazole only post-2020. After atovaquone, 67 patients transitioned to an alternative, most commonly cotrimoxazole (56/67, 84%). There were no breakthrough PJP cases. DISCUSSION: Atovaquone is an alternative PJP prophylaxis agent, used predominantly when cotrimoxazole is not tolerated. Increased usage was related to broader indications, uptake in new patient groups, difficulty tolerating or accessing alternatives, and longer durations. While atovaquone appears safe and effective, regular review of patients receiving it could facilitate reassessment of the initial indication, aiming to reinstate cotrimoxazole whenever appropriate.