编辑推荐：
来自范德堡大学医学院等处的研究人员发表了题为“Azithromycin and the Risk of Cardiovascular Death”的文章，进行了一项回顾性研究，发现阿奇霉素会增加心血管疾病死亡风险，这反驳了之前有关“阿奇霉素对心脏的毒性作用相对较小”的观点，这篇文章发表在NEJM杂志上。
生物通报道：阿奇霉素（Azithromycin）是近年开发生产的大环内酯类抗生素，是在红霉素化学结构上修饰后得到的一种广谱抗生素。1990年9月阿奇霉素在英国上市，1991年底获FDA批准在美国上市。在我国，阿奇霉素制剂也已是临床应用成熟的品种，其原料药、片剂、胶囊已载入2000、2005版中国药典，目前批准生产的剂型还有分散片、颗粒剂、注射剂、输液、干混悬剂和干糖浆剂等。
但是随着研究的深入，此类药物的副作用也被逐渐发现，近期来自范德堡大学医学院等处的研究人员发表了题为“Azithromycin and the Risk of Cardiovascular Death”的文章，进行了一项回顾性研究，发现阿奇霉素会增加心血管疾病死亡风险，这反驳了之前有关“阿奇霉素对心脏的毒性作用相对较小”的观点，这篇文章发表在NEJM杂志上。
文章的第一作者是范德堡大学医学院Wayne A. Ray博士，他指出，虽然增加死亡的机率比较低，但是在统计学上已十分显著了，因此对那些需要抗生素而对阿奇霉素存在高风险的患者，医师处方时应考虑选用另外的抗生素如阿莫西林。
这里的高风险人群是指那些有心力衰竭、糖尿病或曾经有心脏病发作、以及那些曾接受过心脏搭桥手术或植入支架的患者。不过Ray博士还提出，这些人群并不适用于儿童，因为大多数儿童心脏疾病的风险非常的小，另外研究人员还表示对于这种药物会怎样干扰心律，尚不清楚。
在这篇文章中，研究人员分析了1992(阿奇霉素首次引入美国的时间)-2006年间，田纳西州医疗补助计划中30-74岁患者的数据。将347,795 个阿奇霉素5日疗程中的CV死亡和全因死亡事件数与未接受抗生素治疗的1,391,180个匹配对照时期进行了比较。
为了校正治疗适应证的潜在混淆作用，研究者纳入第二个对照组，包括1,348,672次阿莫西林处方、264,626次环丙沙星处方和193,906次左氧氟沙星处方。阿奇霉素和阿莫西林最常见的适应证为耳鼻咽喉感染和支气管炎。
进行对比后，研究人员发现，服用阿奇霉素的患者死亡几率比较高。他们进一步证实，病人在服用阿奇霉素的最初5天时间里，死于心脏疾病的风险是不服用该药物患者的2.5倍。
不过也有科学家指出，这项研究是观察性的，意味着研究人员回顾医疗记录，不是在患者中随机分配到一个治疗组或另一个组而建立的实验，然后监测实验的实施。因此即使最仔细的观察研究，也可能产生误导。
与文章持相同意见的科学家则认为这些包括了患者数量庞大的数据，其结果具有生物学的合理性，给予那些相关的药物也发现能干扰心脏的节律。而且这项研究提出了另一个遏制抗生素过度使用的理由。
对此，目前美国FDA表示将进一步审查这项研究的结果，而且在获得结果后向公众公布。2011年FDA审查了大环内酯类抗生素，并在今年3月修改了Zmax （阿奇霉素口服混悬液缓释药）的“注意事项”部分，增加了关于QT间期延长风险的信息。
（生物通：张迪）
原文摘要：
Azithromycin and the Risk of Cardiovascular Death
Background
Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death.
Methods
We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score–matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions).
Results
During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin.
Conclusions
During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.)
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