AUTHOR=Huang Hui-Bin , Zhu Yi-Bing , Yu Da-Xing 

TITLE=Low-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia: a systematic review and meta-analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1422490

DOI=10.3389/fphar.2024.1422490

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>The recommended standard treatment for Pneumocystis jirovecii pneumonia (PJP) is high-dose trimethoprim-sulfamethoxazole (TMP-SMX) (15–20 mg/kg/d TMP). However, the standard regimen may cause a high incidence of dose-related adverse events (AEs). Therefore, we aimed to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose TMP-SMX regimens (&lt;15 mg/kg/d of TMP) compared with the standard regimen in patients with PJP.</p></sec><sec><title>Methods</title><p>We searched PubMed, Embase, and the Cochrane database for relevant articles from inception to 10 March 2024. Studies were included if they focused on PJP patients receiving a low-dose TMP-SMX regimen compared with a standard regimen. The primary outcome was mortality. We assessed study quality and performed subgroup analysis and sensitivity analysis to explore potential heterogeneity among the included studies.</p></sec><sec><title>Results</title><p>Seven studies were included. Overall, the low-dose regimen significantly reduced the risk of mortality (odds ratio [OR] = 0.49; 95% CI, 0.30–0.80; <italic>I</italic><sup>2</sup> = 16%; <italic>P</italic> = 004). This finding was confirmed in further sensitivity and subgroup analyses. The low-dose regimen also significantly reduced total AEs (OR = 0.43; 95% CI, 0.29–0.62; <italic>I</italic><sup>2</sup> = 0%; <italic>P </italic>&lt; 0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13 to 0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (<italic>P</italic> = 0.002), fewer patients requiring dose reductions (<italic>P</italic> = 0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (<italic>P</italic> = 0.06).</p></sec><sec><title>Conclusion</title><p>The limited available evidence suggests that a low-dose TMP-SMX regimen significantly reduced mortality and total AEs in PJP patients. Thus, it is one of the potentially promising therapies to PJP and more high-quality and multi-center randomized trials should be conducted in the future.</p></sec>