JAMA：阿奇霉素的治疗可维持肠道长期较低的带菌率
2012-03-16 MedSci MedSci原创
3月14日，国际著名杂志《美国医学会杂志》JAMA在线刊登了国外研究者的一项研究“Association Between Azithromycin Therapy and Duration of Bacterial Shedding Among Patients With Shiga Toxin–Producing Enteroaggregative Escherichia coli O104:H
3月14日，国际著名杂志《美国医学会杂志》JAMA在线刊登了国外研究者的一项研究“Association Between Azithromycin Therapy and Duration of Bacterial Shedding Among Patients With Shiga Toxin–Producing Enteroaggregative Escherichia coli O104:H4，”，该研究披露，2011年5月在德国的大肠杆菌的疫情爆发中，阿奇霉素的治疗与较低的长期带菌率及大便样本中细菌流泄时间较短有关。
文章的作者写道：“自2011年5月以来，一场大规模的产生志贺毒素的大肠杆菌（STEC）疫情的爆发在德国造成了3816起有记录的感染，其中包括845例被证实的溶血性尿毒综合征 [HUS；这是一种以红细胞崩解和肾脏衰竭为特征的疾病]。根据现有的建议，对STEC感染进行抗菌素治疗是受到劝阻的，因为这种疗法可能会增加HUS加剧的风险。”研究人员补充说，长期带菌会引起持续性的腹泻症状。
就此次疫情爆发而言，长期携带STEC的数据尚未公布。德国吕贝克Schleswig-Holstein大学医院的Martin Nitschke， M.D.及其同事对得了这种感染的病人的细菌流泄时间进行了分析，并将那些接受了阿奇霉素治疗的患者与没有接受抗菌素治疗的患者进行了比较。在此次疫情爆发中有相当多的病人接受了预防性的阿奇霉素治疗，这是用有C5抗体eculizumab的治疗方案的一部分。该研究包括了65名罹患STEC感染的病人，其中包括在2011年5月15日至7月26日间患有HUS的病人与感染了STEC但没有HUS表现的门诊病人以及那些在出现临床症状之后被平均监控了 39.3天的病人。
最初的阿奇霉素治疗组包括了22位病人，而对照组则包括了43位未经抗菌素治疗的患者。平均来说，接受阿奇霉素治疗的病人是在出现临床症状之后11.8天时开始接受治疗的。两组间没有明显的年龄或性别分布上的差异。
研究人员发现，STEC携带者的数量在那些接受了阿奇霉素治疗的病人中明显要少。 “在第21天的时候，STEC携带率在最初治疗组的病人中为31.8%，而在没有治疗组的病人中则为83.7%。治疗组中患者的长期带菌率（在第28天时）为4.5%，而在无治疗组中则为81.4%。在第35天时，治疗组中没有一位患者为STEC的携带者，而所有患者在完成了14天的治疗之后依然为 STEC阴性。相反，在对照组中，43位患者中有25人（57.7%）在出现临床症状之后第42天时为STEC的携带者。”
另外，所观察到的接受阿奇霉素治疗患者大便样本中STEC的快速清除及在对照组中长期携带STEC的高比例使得有关人员决定对15名仍有症状的患者给予阿奇霉素治疗。在治疗结束之后，所有患者至少有3次STEC阴性的大便样本。没有迹象表明因为阿奇霉素治疗而诱发了HUS。
Association Between Azithromycin Therapy and Duration of Bacterial Shedding Among Patients With Shiga Toxin–Producing Enteroaggregative Escherichia coli O104:H4
Martin Nitschke, MD; Friedhelm Sayk, MD; Christoph Härtel, MD; Rahel Tabea Roseland; Susanne Hauswaldt, MD; Jürgen Steinhoff, MD; Klaus Fellermann, MD; Inge Derad, MD; Peter Wellhöner, MD; Jürgen Büning, MD; Bettina Tiemer, MD; Alexander Katalinic, MD; Jan Rupp, MD; Hendrik Lehnert, MD; Werner Solbach, MD; Johannes K.-M. Knobloch, MD
Context An outbreak of Shiga toxin–producing enteroaggregative Escherichia coli (STEC O104:H4) infection with a high incidence of hemolytic uremic syndrome (HUS) occurred in Germany in May 2011. Antibiotic treatment of STEC infection is discouraged because it might increase the risk of HUS development. However, antibiotic therapy is widely used to treat enteroaggregative E coli infection. In the German outbreak, a substantial number of patients received prophylactic azithromycin treatment as part of a therapeutic regimen with the C5 antibody eculizumab.
Objective To analyze the duration of bacterial shedding in patients with STEC infection who did and did not receive oral azithromycin therapy.
Design, Setting, and Patients At a single center in Lübeck, Germany, 65 patients with STEC infection, including patients with HUS as well as STEC-infected outpatients without manifestation of HUS, were investigated between May 15 and July 26, 2011, and were monitored for a mean of 39.3 days after onset of clinical symptoms.
Main Outcome Measure Carriage of STEC after azithromycin therapy. Results Twenty-two patients received oral azithromycin and 43 patients did not receive antibiotic treatment. Among antibiotic-treated patients, long-term STEC carriage (>28 days) was observed in 1 of 22 patients (4.5%; 95% CI, 0%-13.3%) compared with 35 of 43 patients (81.4%; 95% CI, 69.8%-93.0%) who were not treated with antibiotics (P < .001). All 22 patients receiving azithromycin treatment had at least 3 STEC-negative stool specimens after the completion of treatment, and no recurrence of STEC was observed in these patients. As proof of principle, 15 patients who initially were not treated with antibiotics and were long-term STEC carriers were treated with oral azithromycin given for 3 days and subsequently had negative stool specimens.
Conclusion Treatment with azithromycin was associated with a lower frequency of long-term STEC O104:H4 carriage.
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