Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei.
College of Medicine, I-Shou University and Department of Internal Medicine, E-Da Hospital, Kaohsiung Department of Internal Medicine, National Taiwan University Hospital, Taipei.
Clin Infect Dis. 2015 Feb 15;60(4):566-77. doi: 10.1093/cid/ciu914. Epub 2014 Nov 18.
Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics.
Between January 2001 and November 2011, a total of 10 684 100 patients were prescribed oral azithromycin, clarithromycin, moxifloxacin, levofloxacin, ciprofloxacin, or amoxicillin-clavulanate at outpatient visits. A logistic regression model adjusted for propensity score was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for adverse cardiac outcomes occurring within 7 days after the initiation of antibiotic treatment.
Compared with amoxicillin-clavulanate treatment, the use of azithromycin and moxifloxacin was associated with significant increases in the risks of ventricular arrhythmia and cardiovascular death. The adjusted ORs for ventricular arrhythmia were 4.32 (95% CI, 2.95-6.33) for azithromycin, 3.30 (95% CI, 2.07-5.25) for moxifloxacin, and 1.41 (95% CI, .91-2.18) for levofloxacin. For cardiovascular death, the adjusted ORs for azithromycin, moxifloxacin, and levofloxacin were 2.62 (95% CI, 1.69-4.06), 2.31 (95% CI, 1.39-3.84), and 1.77 (95% CI, 1.22-2.59), respectively. No association was noted between clarithromycin or ciprofloxacin and adverse cardiac outcomes.
Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.
先前的研究表明，阿奇霉素和左氧氟沙星与心血管死亡率的增加有关。而同一类药物中替代药物（包括克拉霉素和莫西沙星）的风险尚不清楚。我们利用台湾全民健康保险数据库进行了一项全国性的基于人群的研究，比较了使用这些抗生素的患者发生室性心律失常和心血管死亡的风险。
2001 年 1 月至 2011 年 11 月间，共有 10 684 100 名患者在门诊就诊时被处方口服阿奇霉素、克拉霉素、莫西沙星、左氧氟沙星、环丙沙星或阿莫西林-克拉维酸。采用倾向评分调整的 logistic 回归模型计算抗生素治疗开始后 7 天内不良心脏结局的比值比（OR）和 95%置信区间（CI）。
与阿莫西林-克拉维酸治疗相比，阿奇霉素和莫西沙星的使用与室性心律失常和心血管死亡风险的显著增加相关。阿奇霉素的调整 OR 为 4.32（95%CI，2.95-6.33），莫西沙星的调整 OR 为 3.30（95%CI，2.07-5.25），左氧氟沙星的调整 OR 为 1.41（95%CI，0.91-2.18）。对于心血管死亡，阿奇霉素、莫西沙星和左氧氟沙星的调整 OR 分别为 2.62（95%CI，1.69-4.06）、2.31（95%CI，1.39-3.84）和 1.77（95%CI，1.22-2.59）。克拉霉素或环丙沙星与不良心脏结局无关。
当开处方阿奇霉素和莫西沙星时，医疗保健专业人员应考虑到室性心律失常和心血管死亡风险略有增加但具有统计学意义。需要进一步的研究来确定死亡率的增加是由药物引起的，还是与感染的严重程度或病原体本身有关。
