As Pneumocystis pneumonia (PCP) increasingly develops in non-HIV patients without established immunocompromising factors, the study examined the evolving predisposing factors and at-risk medications.

This multicenter retrospective study included non-HIV PCP at seven clinical centers from 2016–2023. Patients were categorized by exposed medications and underlying predisposing diseases. Demographic characteristics, disease severity, treatment approaches, and outcomes were reported.

470 non-HIV PCP were identified, and 420 probable cases were included for analysis. The proportion of PCP without established high-risk medications increased from 47% in 2016 to 61% by 2023. 209 (49.8%) received established high-risk medications, 106 (25.2%) with suspected at-risk medications, and 155 (36.9%) with no at-risk medications. Subjects with established high-risk medications were more likely to have hematological malignancies (50.2%, P<0.001). Those with suspected at-risk medications had higher rates of solid cancers (63.2%, P<0.001) and transplantation (24.5%, P<0.001). Overall mortality rates were 43.8% at 60-day, with comparable mortality across medication groups (log-rank P=0.08) but significant differences by disease category (log-rank P<0.001), with solid cancers exhibiting the worst outcome (58.0%).

The epidemiology of non-HIV PCP is evolving beyond traditional risk categories. Both emerging high-risk medications and predisposing comorbidities might require further investigation and addressed in prophylaxis guidelines.