Association between low-dose trimethoprim-sulfamethoxazole blood concentration and clinical outcomes in non-HIV patients with Pneumocystis jirovecii pneumonia: a retrospective cohort study

Trimethoprim-sulfamethoxazole (SMX-TMP) represents the first-line treatment for non-human immunodeficiency virus (non-HIV) patients with Pneumocystis jirovecii pneumonia (PJP). However, the relationship between SMX peak serum concentrations (Cmax) and clinical outcomes of PJP is not clear yet. This study aim to investigate the impact of initial Cmax of SMX on clinical outcomes non-HIV patients with PJP who were predominantly treated with low-dose SMX-TMP, and to evaluate related adverse drug reactions (ADRs), providing evidence for optimal clinical medication strategies. A retrospective analysis was conducted on 66 non-HIV patients with PJP who received SMX-TMP treatment and had SMX Cmax monitoring results at Hunan University of Medicine General Hospital from January 2022 to December 2024. Patients were divided into high-concentration (SMX Cmax >100 µg/mL) and low-concentration (SMX Cmax ≤100 µg/mL) groups. Statistical analyses were performed to compare clinical improvement rates, 28-day mortality rates, and ADR incidence between the two groups. Factors influencing SMX Cmax, including daily dose and glomerular filtration rate (GFR), were also analyzed. The median SMX Cmax was 108 (78.6–151.0) µg/mL among the 66 patients, with 37 patients (56.66%) achieving concentrations above 100 µg/mL. The overall patients received SMX median daily dose was 49.2 (40.0, 63.2) mg/kg, in the group of patients with high concentration, the median daily dose was 56.1 (43.6, 66.7) mg/kg. All these values are lower than the daily dose of 75–100 mg/kg recommended by the guidelines. Only 7 patients (10.61%) meeting guideline recommendations dosage. Compared with the low-concentration group, the high-concentration group showed significantly higher improvement rates (83.8% vs. 55.2%, P = 0.011) and significantly lower 28-day mortality rates (2.7% vs. 20.7%, P = 0.038). Multivariate logistic regression analysis identified SMX Cmax as an independent predictor of patient improvement (OR = 4.2, 95% CI: 1.34–13.13). Subgroup analyses revealed no significant interactions with grouping factor and SMX concentrations. Correlation analysis demonstrated a moderate positive correlation between SMX daily dose and Cmax (r = 0.458, P < 0.01), while GFR showed no significant correlation with blood concentrations. When stratified by SMX Cmax >150 µg/mL, no significant differences were observed in ADRs including rash, gastrointestinal discomfort, hepatic/renal dysfunction, thrombocytopenia, leukopenia, or hyperkalemia between concentration groups, absolute ADRs incidence rates in the high-concentration group were generally higher than in the low-concentration group. In non-HIV PJP patients predominantly receiving low-dose SMX-TMP therapy, SMX Cmax >100 µg/mL was associated with improved clinical outcomes. This study observed that most patients did not achieve guideline-recommended dosing, yet many still attained therapeutic SMX concentrations, suggesting that weight-based standard dosing alone may be insufficient for Chinese populations. Routine therapeutic drug monitoring (TDM) of SMX should be implemented in clinical practice to achieve individualized precision dosing.