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背景包括磺胺甲基异口恶唑在内的部分抗菌药限制了华法林的代谢,可增加出血风险。本研究调查了老年患者使用华法林与治疗尿路感染常用抗菌药联合用药所导致的出血风险,主要聚焦于磺胺甲基异口恶唑。方法使用1997-04-01—2007-03-31加拿大多伦多卫生保健基础数据,对持续用华法林治疗的≥66岁的居民进行识别。均因上胃肠道出血而住院。针对每个病例,我们挑选10例与之年龄、性别匹配对照受试者。针对上胃肠道出血前14 d内暴露于磺胺甲基异口恶唑、阿莫西林、氨苄青霉素、盐酸环丙沙星、呋喃妥因和氟哌酸者,计算其校正后优势比(aORs)。结果共识别出134 637例用华法林病人,其中2 151例因上胃肠道出血住院。近期用磺胺甲基异口恶唑病例上胃肠道出血的发生率可为对照组4倍〔OR=3.84,95%CI(2.33,6.33)〕。用环丙沙星也与风险增加相关〔OR=1.94,95%CI(1.28,2.95)〕,但与阿莫西林或氨卡青霉素〔OR=1.37,95%CI(0.92,2.05)〕、呋喃妥因〔OR=1.40,95%CI(0.71,2.75)〕或氟哌酸〔OR=0.38,95%CI(0.12,1.26)〕无显著相关。与阿莫西林或氨卡青霉素比较,用磺胺甲基异口恶唑与3倍风险相关〔OR=2.80,95%CI(1.48,5.32)〕。结论用华法林的老年病人,与用其他常用抗菌药相比,磺胺甲基异口恶唑导致上胃肠道出血风险明显升高。对用华法林的病人,医生应尽可能选择替代抗菌药。
Background Some antimicrobials, including sulfamethoxazole, limit the metabolism of warfarin and increase the risk of bleeding. This study investigated the risk of bleeding associated with the use of warfarin in combination with commonly used antimicrobials for the treatment of urinary tract infections in elderly patients, with a focus on sulfamethoxazole. Methods Using the basic health care data from Toronto, Canada, 1997-04-01-2007-03-31, residents ≥66 years of age treated with warfarin were identified. All due to gastrointestinal bleeding and hospitalization. For each case, we selected 10 subjects who were matched by age and sex. The corrected odds ratios (aORs) were calculated for those exposed to sulfamethoxazole, amoxicillin, ampicillin, ciprofloxacin hydrochloride, nitrofurantoin and norfloxacin within 14 days prior to upper gastrointestinal bleeding. A total of 134 637 warfarin patients were identified, of whom 2 151 were hospitalized for upper gastrointestinal bleeding. The recent incidence of gastrointestinal bleeding with sulfamethoxazole is 4 times more likely than the control (OR = 3.84, 95% CI 2.33, 6.33). Ciprofloxacin was also associated with increased risk (OR = 1.94, 95% CI 1.28, 2.95) but not with amoxicillin or ampicillin (OR = 1.37, 95% CI 0.92, 2.05) (OR = 1.40, 95% CI (0.71, 2.75)] or norfloxacin [OR = 0.38, 95% CI (0.12, 1.26)]. Compared with amoxicillin or ampicillin, sulfamethoxazole was associated with a 3 -fold risk [OR = 2.80, 95% CI (1.48, 5.32)]. Conclusions In warfarin elderly patients, the risk of upper gastrointestinal bleeding was significantly increased with sulfamethoxazole compared to other commonly used antibacterials. For patients on warfarin, doctors should try their best to substitute for antimicrobials.