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与旅行者腹泻单剂量抗生素治疗相关的粪便微生物群功能基因效应

Fecal Microbiota Functional Gene Effects Related to Single-Dose Antibiotic Treatment of Travelers' Diarrhea.

作者信息

Johnson Ryan C, Van Nostrand Joy D, Tisdale Michele, Swierczewski Brett, Simons Mark P, Connor Patrick, Fraser Jamie, Melton-Celsa Angela R, Tribble David R, Riddle Mark S

机构信息

Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.

出版信息

Open Forum Infect Dis. 2021 May 28;8(6):ofab271. doi: 10.1093/ofid/ofab271. eCollection 2021 Jun.

Abstract

BACKGROUND

Travelers' diarrhea (TD) is common among military personnel deployed to tropical and subtropical regions. It remains unclear how TD and subsequent antibiotic treatment impact the resident microflora within the gut, especially given increased prevalence of antibiotic resistance among enteric pathogens and acquisition of multidrug-resistant organisms. We examined functional properties of the fecal microflora in response to TD, along with subsequent antibiotic treatment.

METHODS

Fecal samples from US and UK military service members deployed to Djibouti, Kenya, and Honduras who presented with acute watery diarrhea were collected. A sample was collected at acute presentation to the clinic (day 0, before antibiotics), as well as 7 and/or 21 days following a single dose of antibiotics (azithromycin [500 mg], levofloxacin [500 mg], or rifaximin [1650 mg], all with loperamide). Each stool sample underwent culture and TaqMan reverse transcription polymerase chain reaction analyses for pathogen and antibiotic resistance gene detection. Purified DNA from each sample was analyzed using the HumiChip3.1 functional gene array.

RESULTS

In total, 108 day 1 samples, 50 day 7 samples, and 94 day 21 samples were available for analysis from 119 subjects. Geographic location and disease severity were associated with distinct functional compositions of fecal samples. There were no overt functional differences between pre- and postantibiotic treatment samples, nor was there increased acquisition of antibiotic resistance determinants for any of the antibiotic regimens.

CONCLUSIONS

These results indicate that single-dose antibiotic regimens may not drastically alter the functional or antibiotic resistance composition of fecal microflora, which should inform clinical practice guidelines and antimicrobial stewardship.

CLINICAL TRIALS REGISTRATION NUMBER

NCT01618591.

摘要

背景

旅行者腹泻(TD)在部署到热带和亚热带地区的军事人员中很常见。目前尚不清楚TD及其后的抗生素治疗如何影响肠道内的常驻微生物群,特别是考虑到肠道病原体中抗生素耐药性的患病率增加以及多重耐药菌的获得。我们研究了粪便微生物群对TD以及随后抗生素治疗的功能特性。

方法

收集了部署到吉布提、肯尼亚和洪都拉斯的美国和英国军人出现急性水样腹泻的粪便样本。在诊所急性就诊时(第0天,使用抗生素前)以及单剂量抗生素(阿奇霉素[500mg]、左氧氟沙星[500mg]或利福昔明[1650mg],均与洛哌丁胺联用)治疗7天和/或21天后采集样本。每个粪便样本进行培养和TaqMan逆转录聚合酶链反应分析,以检测病原体和抗生素耐药基因。使用HumiChip3.1功能基因阵列分析每个样本的纯化DNA。

结果

总共从119名受试者中获得了108份第1天的样本、50份第7天的样本和94份第21天的样本用于分析。地理位置和疾病严重程度与粪便样本的不同功能组成相关。抗生素治疗前后的样本之间没有明显的功能差异,任何一种抗生素治疗方案也没有增加抗生素耐药决定因素的获得。

结论

这些结果表明,单剂量抗生素方案可能不会大幅改变粪便微生物群的功能或抗生素耐药性组成,这应为临床实践指南和抗菌药物管理提供参考。

临床试验注册号

NCT01618591。

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