Preyra Rebecca, Eddin Lujain Ez, Ahmadi Fatemeh, Jafari Atefeh, Muanda Flory T
Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.
ICES Western, London, ON, Canada.
Br J Clin Pharmacol. 2025 Jun;91(6):1632-1648. doi: 10.1111/bcp.70051.
Sulfamethoxazole-trimethoprim (SMX-TMP) is a widely used antibiotic for treating bacterial infections, but its safety in adult outpatients remains understudied. This systematic review and meta-analysis evaluated the safety profile of SMX-TMP and identified critical research gaps. The pharmacovigilance study aimed to validate and extend findings from meta-analyses to better understand the real-world safety of SMX-TMP.
We searched MEDLINE and Embase up to 12 August 2024, to identify studies comparing adverse drug events (ADEs) following SMX-TMP vs. other antibiotics in adult outpatients. Meta-analyses were performed where data allowed. A pharmacovigilance study using the Food and Drug Administration Adverse Event Reporting System was conducted to supplement our findings.
Our review, which included 43 studies, found SMX-TMP had a nearly 3-fold higher risk of rash compared to other antibiotics (pooled risk ratio 2.56, 95% confidence interval [1.69, 3.89], I = 0%, n = 4458 participants, 24 randomized control trials). Pharmacovigilance data confirmed a higher frequencies of skin disorders and other ADEs compared to various comparator drugs. Compared to azithromycin, SMX-TMP was associated with a 5-fold increase in Stevens-Johnson syndrome, a 3-fold increase in toxic epidermal necrolysis, and a 10-fold increase in drug reaction with eosinophilia and systemic symptoms. Additionally, SMX-TMP showed a 10-fold increase in reports of pancytopenia, a 6-fold increase in neutropenia, a 4-fold increase in both thrombocytopenia and aplastic anaemia, a 56-fold increase in hyperkalaemia, and a 10-fold increase in hyponatraemia.
Our meta-analyses and pharmacovigilance study suggested SMX-TMP was associated with increased risk of ADEs compared to other antibiotics including amoxicillin/clavulanate, azithromycin and nitrofurantoin. Further robust research is essential to confirm these safety signals and guide clinical practice.
磺胺甲恶唑-甲氧苄啶（SMX-TMP）是一种广泛用于治疗细菌感染的抗生素，但其在成年门诊患者中的安全性仍未得到充分研究。本系统评价和荟萃分析评估了SMX-TMP的安全性概况，并确定了关键的研究空白。药物警戒研究旨在验证和扩展荟萃分析的结果，以更好地了解SMX-TMP在现实世界中的安全性。
我们检索了截至2024年8月12日的MEDLINE和Embase，以识别比较成年门诊患者使用SMX-TMP与其他抗生素后药物不良事件（ADEs）的研究。在数据允许的情况下进行荟萃分析。使用美国食品药品监督管理局不良事件报告系统进行了一项药物警戒研究，以补充我们的研究结果。
我们的综述纳入了43项研究，发现与其他抗生素相比，SMX-TMP出现皮疹的风险高出近3倍（合并风险比2.56，95%置信区间[1.69，3.89]，I=0%，n=4458名参与者，24项随机对照试验）。药物警戒数据证实，与各种对照药物相比，皮肤疾病和其他ADEs的发生率更高。与阿奇霉素相比,SMX-TMP与史蒂文斯-约翰逊综合征增加5倍、中毒性表皮坏死松解症增加3倍、伴有嗜酸性粒细胞增多和全身症状的药物反应增加10倍有关。此外，SMX-TMP全血细胞减少报告增加10倍、中性粒细胞减少增加6倍、血小板减少和再生障碍性贫血均增加4倍、高钾血症增加56倍、低钠血症增加10倍。
我们的荟萃分析和药物警戒研究表明，与包括阿莫西林/克拉维酸、阿奇霉素和呋喃妥因在内的其他抗生素相比,SMX-TMP与ADEs风险增加有关。进一步开展有力的研究对于确认这些安全信号并指导临床实践至关重要。
