The role of cancer and immunosuppression in pneumocystis pneumonia: a large comprehensive population-based study.

Although pneumocystis jirovecii pneumonia (PJP) in non-HIV patients is increasingly recognized, comprehensive data on immunosuppressive drivers remain limited. We conducted a population-based cohort study using a German health insurance's claims data (2015-2023). PJP, comorbidities, immunocompromising conditions and therapies were identified by means of ICD-10-GM-, ATC- and OPS-coded records. 922,200 individuals were assessed for PJP occurrence, hospitalization and 30-day all-cause mortality. An Andersen-Gill model adjusted for key covariates. We identified 171 PJP episodes, with hospitalization in 88.3% and mortality in 24.5%. Frequent immunocompromising causes were hematologic cancers (42.6%), immunosuppressants (28.7%) and steroids (28.7%). Immunosuppression rather than typical CAP risk factors strongly predicted all outcomes (HR 49.9 [31.5-78.9]). Robust associations with PJP occurred for HIV (HR 67.5 [19.4-235]), systemic steroids (> 20 mg prednisone daily equivalent (HR 26.2 [13.2-52.1])) and hematologic cancers (HR 8.5 [4.5-16.3]). Mortality was driven by hematologic cancers (HR 13.9 [4.8-40.2]) and high-dose steroids (HR 8.6 [1.6-47.1]). Malignancy-related immunosuppression and steroids critically affect PJP risk and prognosis.