Leibovici-Weissman Ya'ara, Neuberger Ami, Bitterman Roni, Sinclair David, Salam Mohammed Abdus, Paul Mical
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 49100.
Cochrane Database Syst Rev. 2014 Jun 19;2014(6):CD008625. doi: 10.1002/14651858.CD008625.pub2.
Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs.
To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules.
We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014.
Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial.
Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach.
Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43.51 to -30.03, 19 trials, 1013 participants, moderate quality evidence). Antimicrobial therapy also reduced the total stool volume by 50% (ROM 0.5, 95% CI 0.45 to 0.56, 18 trials, 1042 participants, moderate quality evidence) and reduced the amount of rehydration fluids required by 40% (ROM 0.60, 95% CI 0.53 to 0.68, 11 trials, 1201 participants, moderate quality evidence). The mean duration of fecal excretion of vibrios was reduced by almost three days (MD 2.74 days, 95% CI -3.07 to -2.40, 12 trials, 740 participants, moderate quality evidence).There was substantial heterogeneity in the size of these benefits, probably due to differences in the antibiotic used, the trial methods (particularly effective randomization), and the timing of outcome assessment. The benefits of antibiotics were seen both in trials recruiting only patients with severe dehydration and in those recruiting patients with mixed levels of dehydration. Comparisons of antimicrobials In head-to-head comparisons, there were no differences detected in diarrhoea duration or stool volume for tetracycline compared to doxycycline (three trials, 230 participants, very low quality evidence); or tetracycline compared to ciprofloxacin or norfloxacin (three trials, 259 participants, moderate quality evidence). In indirect comparisons with substantially more trials, tetracycline appeared to have larger benefits than doxycycline, norfloxacin and trimethoprim-sulfamethoxazole for the primary review outcomes.Single dose azithromycin shortened the duration of diarrhoea by over a day compared to ciprofloxacin (MD -32.43, 95% CI -62.90 to -1.95, two trials, 375 participants, moderate quality evidence) and by half a day compared to erythromycin (MD -12.05, 95% CI -22.02 to -2.08, two trials, 179 participants, moderate quality evidence). It was not compared with tetracycline.
AUTHORS' CONCLUSIONS: In treating cholera, antimicrobials result in substantial improvements in clinical and microbiological outcomes, with similar effects observed in severely and non-severely ill patients. Azithromycin and tetracycline may have some advantages over other antibiotics.
霍乱是由霍乱弧菌感染引起的急性水样腹泻，严重时可导致快速脱水和死亡。有效的治疗需要早期诊断并使用口服补液盐或静脉输液进行补液。在本综述中，我们评估了使用抗菌药物治疗霍乱的额外益处。
量化抗菌治疗对霍乱患者的益处，并确定不同类别的抗菌药物或给药方案之间是否存在差异。
我们检索了Cochrane传染病组专业注册库；Cochrane对照试验中央注册库（CENTRAL）；PubMed；EMBASE；非洲医学索引；拉丁美洲及加勒比卫生科学数据库；科学引文索引；对照试验元注册库；世界卫生组织国际临床试验注册平台；会议论文集；以及截至2014年3月的参考文献列表。
针对成人和儿童霍乱患者的随机和半随机对照临床试验，这些试验比较了：1）任何抗菌治疗与安慰剂或不治疗；2）不同抗菌药物的直接比较；或3）相同抗菌药物的不同给药方案或不同治疗持续时间。
两名综述作者独立应用纳入和排除标准，并从纳入的试验中提取数据。腹泻持续时间和粪便量被定义为主要结局。我们计算了连续结局的平均差（MD）或均值比（ROM），并给出95%置信区间（CI），使用随机效应荟萃分析对数据进行汇总。采用GRADE方法评估证据质量。
本综述纳入了39项试验，共4623名参与者。抗菌药物与安慰剂或不治疗相比总体而言，与安慰剂或不治疗相比，抗菌治疗使腹泻平均持续时间缩短了约一天半（MD -36.77小时，95%CI -43.51至-30.03，19项试验，1013名参与者，中等质量证据）。抗菌治疗还使粪便总量减少了50%（ROM 0.5，95%CI 0.45至0.56，18项试验，1042名参与者，中等质量证据），并使所需补液量减少了40%（ROM 0.60，95%CI 0.53至0.68，11项试验，1201名参与者，中等质量证据）。霍乱弧菌粪便排泄的平均持续时间缩短了近三天（MD 2.74天，95%CI -3.07至-2.40，12项试验，740名参与者，中等质量证据）。这些益处的大小存在很大异质性，可能是由于所用抗生素、试验方法（特别是有效随机化）以及结局评估时间的差异。在仅招募重度脱水患者的试验和招募不同脱水程度患者的试验中均观察到了抗生素的益处。抗菌药物的比较在直接比较中，与多西环素相比，四环素在腹泻持续时间或粪便量方面未发现差异（3项试验，230名参与者，极低质量证据）；与环丙沙星或诺氟沙星相比，四环素也未发现差异（3项试验，259名参与者，中等质量证据）。在有更多试验的间接比较中，对于主要综述结局，四环素似乎比多西环素、诺氟沙星和甲氧苄啶-磺胺甲恶唑有更大益处。与环丙沙星相比，单剂量阿奇霉素使腹泻持续时间缩短了一天多（MD -32.43，95%CI -62.90至-1.95，2项试验，375名参与者，中等质量证据），与红霉素相比缩短了半天（MD -12.05，95%CI -22.02至-2.08，2项试验，179名参与者，中等质量证据）。未将其与四环素进行比较。
在治疗霍乱时，抗菌药物可使临床和微生物学结局有显著改善，在重症和非重症患者中均观察到类似效果。阿奇霉素和四环素可能比其他抗生素有一些优势。
