Huang Hui-Bin, Shi Jia-Heng, Hu Yan-Ge, Zhu Yi-Bing, Yu Da-Xing
Department of Critical Care Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2025 Jul 15;16:1545436. doi: 10.3389/fphar.2025.1545436. eCollection 2025.
Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line prophylactic agent against pneumonia (PJP). However, the standard regimen is often discontinued due to its drug-associated adverse events (AEs), especially in immunocompromised patients without HIV infection. Therefore, we aimed to investigate the efficacy and safety of a low-dose regimen of TMP-SMX against PJP prophylaxis in patients without infection.
We searched PubMed, Embase, Wanfang, China National Knowledge Infrastructure, Web of Science, and the Cochrane database for relevant articles from inception to 15 October 2024. Studies were included if they reported the safety and efficacy of using TMP-SMX in PJP prophylaxis in patients without HIV infection. The primary outcome was the discontinuation rate. We assessed study quality and performed sensitivity and subgroup analysis to explore potential heterogeneity among the included studies.
Seventeen studies with 4,890 patients were included. These studies were low to modest in quality. Overall, the incidence of PJP in the included studies was rare and was similar between the low- and standard-dose groups. However, the low-dose regimen significantly reduced the risk of discontinuation rate (odds ratio [OR] = 0.38; 95% CI, 0.27-0.52; = 0%; < 0.00001). Further sensitivity and subgroup analyses confirmed this finding. Estimation of the combined discontinuation rate for patients receiving low-dose TMP-SMX was 10% (95% CI, 4%-16%). The low-dose regimen also significantly reduced total AEs (OR = 0.33; 95% CI, 0.24-0.46; = 22%; < 0.00001) and improved the incidence of most specific AEs (ORs ranged from 0.24 to 0.67), especially in outcomes of fever, rash, thrombocytopenia, hyponatremia, and liver and renal function ( values ranged from 0.0001 to 0.02).
Our findings suggested that a low-dose TMP-SMX regimen is safe and significantly reduces the discontinuation rate and total AEs compared to the standard regimen against PJP in HIV-uninfected patients. Thus, it is a potentially promising prophylactic regimen, and more well-designed, high-quality research should be conducted.
甲氧苄啶-磺胺甲恶唑（TMP-SMX）是预防肺炎（肺孢子菌肺炎，PJP）的推荐一线用药。然而，由于其药物相关不良事件（AE），标准治疗方案常被中断，尤其是在未感染HIV的免疫功能低下患者中。因此，我们旨在研究低剂量TMP-SMX方案在无感染患者中预防PJP的疗效和安全性。
我们检索了PubMed、Embase、万方、中国知网、Web of Science和Cochrane数据库，查找从数据库建立至2024年10月15日的相关文章。纳入的研究需报告在未感染HIV的患者中使用TMP-SMX预防PJP的安全性和疗效。主要结局是停药率。我们评估了研究质量，并进行了敏感性和亚组分析，以探讨纳入研究之间潜在的异质性。
纳入了17项研究，共4890例患者。这些研究质量低至中等。总体而言，纳入研究中PJP的发生率较低，低剂量组和标准剂量组相似。然而，低剂量方案显著降低了停药率风险（优势比[OR]=0.38；95%置信区间，0.27-0.52；I²=0%；P<0.00001）。进一步的敏感性和亚组分析证实了这一发现。接受低剂量TMP-SMX治疗患者的联合停药率估计为10%（95%置信区间，4%-16%）。低剂量方案还显著降低了总不良事件发生率（OR=0.33；95%置信区间，0.24-0.46；I²=22%；P<0.00001），并改善了大多数特定不良事件的发生率（OR范围为0.24至0.67），尤其是在发热、皮疹、血小板减少、低钠血症以及肝肾功能方面（P值范围为0.0001至0.02）。
我们的研究结果表明，与标准方案相比，低剂量TMP-SMX方案在未感染HIV的患者中预防PJP时是安全的，且显著降低了停药率和总不良事件发生率。因此，它是一种潜在有前景的预防方案，应开展更多设计良好、高质量的研究。
