Lane Michael A, Zeringue Angelique, McDonald Jay R
Washington University, St. Louis, Mo.
Washington University, St. Louis, Mo; St. Louis Veterans Affairs Medical Center, St. Louis, Mo.
Am J Med. 2014 Jul;127(7):657-663.e2. doi: 10.1016/j.amjmed.2014.01.044. Epub 2014 Mar 19.
Antibiotics may interact with warfarin, increasing the risk for significant bleeding events.
This is a retrospective cohort study of veterans who were prescribed warfarin for 30 days without interruption through the US Department of Veterans Affairs between October 1, 2002 and September 1, 2008. Antibiotics considered to be high risk for interaction with warfarin include: trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, levofloxacin, metronidazole, fluconazole, azithromycin, and clarithromycin. Low-risk antibiotics include clindamycin and cephalexin. Risk of bleeding event within 30 days of antibiotic exposure was measured using Cox proportional hazards regression, adjusted for demographic characteristics, comorbid conditions, and receipt of other medications interacting with warfarin.
A total of 22,272 patients met inclusion criteria, with 14,078 and 8194 receiving high- and low-risk antibiotics, respectively. There were 93 and 36 bleeding events in the high- and low-risk groups, respectively. Receipt of a high-risk antibiotic (hazard ratio [HR] 1.48; 95% confidence interval [CI], 1.00-2.19) and azithromycin (HR 1.93; 95% CI, 1.13-3.30) were associated with increased risk of bleeding as a primary diagnosis. TMP/SMX (HR 2.09; 95% CI, 1.45-3.02), ciprofloxacin (HR 1.87; 95% CI, 1.42-2.50), levofloxacin (HR 1.77; 95% CI, 1.22-2.50), azithromycin (HR 1.64; 95% CI, 1.16-2.33), and clarithromycin (HR 2.40; 95% CI, 1.16-4.94) were associated with serious bleeding as a primary or secondary diagnosis. International normalized ratio (INR) alterations were common; 9.7% of patients prescribed fluconazole had INR value >6. Patients who had INR performed within 3-14 days of co-prescription were at a decreased risk of serious bleeding (HR 0.61; 95% CI, 0.42-0.88).
Warfarin users who are prescribed high-risk antibiotics are at higher risk for serious bleeding events. Early INR evaluation may mitigate this risk.
抗生素可能与华法林相互作用，增加严重出血事件的风险。
这是一项回顾性队列研究，研究对象为2002年10月1日至2008年9月1日期间通过美国退伍军人事务部连续30天服用华法林的退伍军人。被认为与华法林相互作用风险高的抗生素包括：甲氧苄啶/磺胺甲恶唑（TMP/SMX）、环丙沙星、左氧氟沙星、甲硝唑、氟康唑、阿奇霉素和克拉霉素。低风险抗生素包括克林霉素和头孢氨苄。使用Cox比例风险回归模型测量抗生素暴露后30天内出血事件的风险，并根据人口统计学特征、合并症以及接受其他与华法林相互作用的药物进行调整。
共有22272名患者符合纳入标准，其中14078名和8194名患者分别接受了高风险和低风险抗生素治疗。高风险组和低风险组分别发生了93例和36例出血事件。接受高风险抗生素（风险比[HR]1.48；95%置信区间[CI]，1.00 - 2.19）和阿奇霉素（HR 1.93；95% CI，1.13 - 3.30）作为主要诊断与出血风险增加相关。TMP/SMX（HR 2.09；95% CI，1.45 - 3.02）、环丙沙星（HR 1.87；95% CI，1.42 - 2.50）、左氧氟沙星（HR 1.77；95% CI，1.22 - 2.50）、阿奇霉素（HR 1.64；95% CI，1.16 - 2.33）和克拉霉素（HR 2.40；95% CI，1.16 - 4.94）与作为主要或次要诊断的严重出血相关。国际标准化比值（INR）改变很常见；服用氟康唑的患者中有9.7%的INR值>6。在联合用药后3 - 14天内进行INR检测的患者发生严重出血的风险降低（HR 0.61；95% CI，0.42 - 0.88）。
服用高风险抗生素的华法林使用者发生严重出血事件的风险更高。早期INR评估可能会降低这种风险。
