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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1422490
Low-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia: a systematic review and meta-analysis
Provisionally accepted- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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 doserelated 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 (<15 mg/kg/d of TMP) compared with the standard regimen in patients with PJP.We searched PubMed, Embase, and the Cochrane database for relevant articles from inception to March 10, 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.Results: 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; I 2 =16%; P=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; I 2 =0%; P<0.0001), and improved the incidence of most specific AEs (ORs ranged from 0.13-0.89). In addition, the low-dose regimen had significantly more patients completing the initial regimen (P=0.002), fewer patients requiring dose reductions (P=0.04), and almost significantly fewer patients requiring a switch to a second-line regimen (P=0.06).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.
Keywords: Pneumocystis jirovecii pneumonia, trimethoprim-sulfamethoxazole, Adverse event, Mortality, Meta-analysis
Received: 24 Apr 2024; Accepted: 30 Oct 2024.
Copyright: © 2024 Huang, Zhu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hui-Bin Huang, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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