Efficacy and safety of echinocandins combined with Trimethoprim-Sulfamethoxazole as first-line treatment for Pneumocystis pneumonia in HIV-infected and non-HIV-infected patients.

INTRODUCTION

Pneumocystis pneumonia (PCP) is a life-threatening infection in both HIV- infected and non-HIV-infected immunocompromised patients. Although Trimethoprim-Sulfamethoxazole (TMP/SMX) combined with echinocandins has been used clinically, whether this combination is superior to TMP/SMX monotherapy as first-line treatment remains inconclusive. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of TMP/SMX plus echinocandins versus TMP/SMX alone in treating PCP. The protocol of this study was registered at the PROSPERO, with registration number CRD420251008762.

METHODS

We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for studies published before February 28, 2025. Included studies involved patients with confirmed PCP infection receiving either TMP/SMX plus echinocandins or TMP/SMX monotherapy. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included overall positive response rate and adverse events (AEs).

RESULTS

Seven studies involving 1963 patients were included. Combination therapy was associated with significantly lower mortality in HIV-infected patients (OR = 0.44, 95% CI: 0.28-0.70, p = 0.0005), but not in non-HIV-infected patients (OR = 1.00, 95% CI: 0.57-1.76, p = 0.99). The treatment response rate was higher with combination therapy in both HIV-infected and non-HIV-infected patients (OR = 2.29, 95% CI: 1.61-3.28, p < 0.00001). The positive response rate was significantly higher in non-HIV-infected (67.54%, 154/228) than in HIV-infected patients (59.00%, 236/400; p < 0.05). No serious AEs were reported in the combination therapy groups.

CONCLUSIONS

The combination of echinocandins with TMP/SMX may reduce mortality in HIV-infected patients with PCP, but does not appear necessary in non-HIV populations. Due to geographical and demographic limitations, these findings should be applied in conjunction with clinical context.