Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes
Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes
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DOI：
10.1093/infdis/jiz299
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发表时间：
2019-11-15
影响因子：
6.4
通讯作者：
Nelson, Eric J.
中科院分区：
文献类型：
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作者：
Alexandrova, Ludmila;Haque, Farhana;Nelson, Eric J.
背景：对抗肠道病原菌耐药性的第一步是建立对抗生素暴露的客观评估。我们的目标是开发和评估的液相色谱-离子阱质谱（LC/MS）的方法，以确定抗生素暴露在患者cholera.Methods：有针对性的LC/MS的优先级列表中产生的药物供应商在孟加拉国的调查。结果：845例霍乱患者中，11%（90例）霍乱弧菌阳性，86%（90例）粪便标本中有1种以上抗生素，52%（90例）粪便标本中有2种以上抗生素。在44例霍乱患者和配对的尿液和粪便标本中，98%的患者检测到>= 1种抗生素，84%的患者检测到>= 2种抗生素，尽管55%的患者自我报告使用了药物。与LC/MS相比，低成本的抗菌检测生物测定法缺乏足够的阴性预测值（10%; 95%置信区间，6%-16%）。在粪便标本中检测到指南推荐的抗生素确实（阿奇霉素; P = 0.040）和不（环丙沙星）与霍乱弧菌抑制相关。非推荐的抗生素（甲硝唑）与厌氧菌减少（即，普雷沃氏菌; P <0.001）。结论：这些发现表明，在本研究中，当试图解释抗生素暴露时，可能没有真正的阴性对照组。
Background: A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera.Methods: A priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh. A study of patients with and those without cholera was conducted to collect and analyze paired urine and stool samples.Results: Among 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed >= 1 antibiotic in 86% and >= 2 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, >= 1 antibiotic was detected in 98% and >= 2 antibiotics were detected in 84%, despite 55% self-reporting medication use. Compared with LC/MS, a low-cost antimicrobial detection bioassay lacked a sufficient negative predictive value (10%; 95% confidence interval, 6%-16%). Detection of guideline-recommended antibiotics in stool specimens did (for azithromycin; P = .040) and did not (for ciprofloxacin) correlate with V. cholerae suppression. A nonrecommended antibiotic (metronidazole) was associated with decreases in anaerobes (ie, Prevotella organisms; P < .001).Conclusion: These findings suggest that there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.