Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection in immunocompromised patients. Non-HIV-related PCP has a rising incidence, faster progression, and higher mortality than HIV-associated cases. Trimethoprim-sulfamethoxazole (TMP/SMX) is first-line, but standard dosing (TMP 15-20 mg/kg/day) is associated with adverse reaction rates of 56%-72%, and prospective evidence is scarce. This prospective, multicentre, observational study aims to compare the efficacy and safety of low-dose (TMP <15 mg/kg/day) versus conventional-dose TMP/SMX for non-HIV-related PCP, and to explore the value of therapeutic drug monitoring in individualising therapy, without interfering with routine clinical decisions.

We plan to enrol 480 patients aged ≥18 years with confirmed non-HIV-related PCP receiving TMP/SMX as initial treatment, excluding those with allergy, prophylaxis, treatment <72 hours, or supratherapeutic dosing. The primary outcome is treatment failure at day 21 (all-cause death or new invasive ventilation). Secondary outcomes include day-8 oxygenation change, 30- and 90-day mortality, regimen completion, adverse events (CTCAE v6.0), and hospital/ICU stay. Propensity score matching will be the main analysis, with inverse probability weighting for sensitivity.

Inclusion Criteria:

1.Age ≥18 years, 2.Meet the diagnostic criteria for non-HIV-related PCP, 3.Receiving TMP/SMX as the initial treatment for PCP, 4.Provide written informed consent to participate in the study.

Exclusion Criteria:

1.Pregnant or breastfeeding women, 2.History of severe allergy or documented intolerance to TMP/SMX, 3.TMP/SMX used for PCP prophylaxis rather than treatment, 4.TMP/SMX treatment duration <72 hours at the time of screening, 5.TMP/SMX administered at a supratherapeutic dose (TMP component >20 mg/kg/day).

This study plans to enrol hospitalised patients aged ≥18 years with confirmed non-HIV-related Pneumocystis jirovecii pneumonia (PCP) who are receiving trimethoprim-sulfamethoxazole (TMP/SMX) as initial therapy. Participants will be recruited from the departments of respiratory medicine, intensive care units, and related clinical wards across 4 participating hospitals in China.