Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.
Int J Antimicrob Agents. 2011 Sep;38(3):197-216. doi: 10.1016/j.ijantimicag.2011.04.016. Epub 2011 Jul 13.
Emergence of resistance to widely used trimethoprim/sulfamethoxazole (TMP/SMX) as well as common adverse events in human immunodeficiency virus (HIV)-infected patients casts interest on combinations of TMP with other sulfonamides. Sulfametrole (SMT) combined with TMP could provide a choice for difficult-to-treat infections, particularly when administered intravenously. The objective of this review was to evaluate the available clinical and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding TMP/SMT, particularly in comparison with TMP/SMX. We reviewed the available evidence retrieved from searches in PubMed/Scopus/Google Scholar and by bibliography hand-searching. In total, 46 eligible studies (most published before 1997) were identified, 7 regarding intravenous (i.v.) TMP/SMT, 24 regarding oral TMP/SMT and 15 providing comparative data for TMP/SMT versus TMP/SMX. The antimicrobial activity of TMP/SMT was similar to TMP/SMX for Gram-positive isolates. A greater percentage of Escherichia coli and Proteus spp. isolates were susceptible to TMP/SMT compared with TMP/SMX. PK/PD data suggest a dosage adjustment of i.v. TMP/SMT in patients with seriously impaired renal function. Four randomised controlled trials and 16 non-comparative studies reported good effectiveness/safety outcomes for oral TMP/SMT in genital ulcers (mainly chancroid), respiratory tract infections and urinary tract infections (UTIs). Moreover, i.v. TMP/SMT was effective against Pneumocystis jiroveci infection in HIV-infected patients, severe pneumonia and UTIs. In one study, hypersensitivity reactions occurred in 18/52 (34.6%) of HIV-infected patients; 2/52 (3.8%) developed psychosis. Gastrointestinal adverse events were mild and rare. Excipients in i.v. TMP/SMT formulations might be less toxic compared with i.v. TMP/SMX formulations, particularly for children. In conclusion, despite the scarcity of contemporary evidence, available data suggest that TMP/SMT could be an alternative treatment option to TMP/SMX, even in serious infections, when administered intravenously.
由于广泛使用的甲氧苄啶/磺胺甲恶唑（TMP/SMX）的耐药性以及人类免疫缺陷病毒（HIV）感染患者的常见不良反应，人们对 TMP 与其他磺胺类药物的联合使用产生了兴趣。磺胺甲恶唑（SMT）与 TMP 联合使用可为治疗困难的感染提供选择，特别是在静脉内给药时。本综述的目的是评估 TMP/SMT 的现有临床和药代动力学/药效学（PK/PD）证据，特别是与 TMP/SMX 相比。我们检索了 PubMed/Scopus/Google Scholar 中的可用证据，并通过文献追溯进行了手工检索。共确定了 46 项合格的研究（大多数发表于 1997 年之前），其中 7 项研究涉及静脉内（i.v.）TMP/SMT，24 项研究涉及口服 TMP/SMT，15 项研究提供了 TMP/SMT 与 TMP/SMX 比较的数据。TMP/SMT 对革兰阳性菌的抗菌活性与 TMP/SMX 相似。与 TMP/SMX 相比，更多的大肠杆菌和变形杆菌属分离株对 TMP/SMT 敏感。PK/PD 数据表明，严重肾功能受损的患者需要调整 i.v. TMP/SMT 的剂量。四项随机对照试验和 16 项非对照研究报告了口服 TMP/SMT 在生殖器溃疡（主要是软性下疳）、呼吸道感染和尿路感染（UTIs）中的良好疗效/安全性结果。此外，i.v. TMP/SMT 对 HIV 感染患者的肺孢子菌感染、严重肺炎和 UTIs 有效。在一项研究中，52 例 HIV 感染患者中有 18 例（34.6%）发生过敏反应；2 例（3.8%）发生精神病。胃肠道不良反应轻微且罕见。与 i.v. TMP/SMX 制剂相比，i.v. TMP/SMT 制剂的赋形剂可能毒性更小，特别是对儿童而言。总之，尽管缺乏现代证据，但现有数据表明，TMP/SMT 可能是 TMP/SMX 的替代治疗选择，甚至在严重感染时，也可选择静脉内给药。
