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

Abstract

<h4>Introduction</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.