{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:53:44Z","timestamp":1793076824420,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP5OD019893"],"award-info":[{"award-number":["DP5OD019893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2013ion trap mass spectrometry (LC\/MS) method to determine antibiotic exposure in patients with cholera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed \u22651 antibiotic in 86% and \u22652 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, \u22651 antibiotic was detected in 98% and \u22652 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%\u201316%). 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 &lt; .001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiz299","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T19:10:13Z","timestamp":1560280213000},"page":"1655-1666","source":"Crossref","is-referenced-by-count":28,"title":["Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes"],"prefix":"10.1093","volume":"220","author":[{"given":"Ludmila","family":"Alexandrova","sequence":"first","affiliation":[{"name":"Vincent Coates Foundation Mass Spectrometry Laboratory, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhana","family":"Haque","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Disease Control, and Research, Ministry of Health and Family Welfare, Government of Bangladesh, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida, Gainesville"},{"name":"Department of Environmental and Global Health, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashton C","family":"Marrazzo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida, Gainesville"},{"name":"Department of Environmental and Global Health, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A","family":"Grembi","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasavi","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Hryckowian","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"Adams","sequence":"additional","affiliation":[{"name":"Vincent Coates Foundation Mass Spectrometry Laboratory, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Shah A","family":"Siddique","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraful I","family":"Khan","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdausi","family":"Qadri","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmudur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Disease Control, and Research, Ministry of Health and Family Welfare, Government of Bangladesh, Dhaka, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred M","family":"Spormann","sequence":"additional","affiliation":[{"name":"Department of Civil and Environmental Engineering, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary K","family":"Schoolnik","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allis","family":"Chien","sequence":"additional","affiliation":[{"name":"Vincent Coates Foundation Mass Spectrometry Laboratory, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Stanford University, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"key":"2019101003483980700_CIT0001","doi-asserted-by":"crossref","first-page":"e564","DOI":"10.1016\/S2214-109X(15)00151-5","article-title":"Pathogen-specific burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)","volume":"3","author":"Platts-Mills","year":"2015","journal-title":"Lancet Glob Health"},{"key":"2019101003483980700_CIT0002","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"2019101003483980700_CIT0003","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nature13738","article-title":"Members of the human gut microbiota involved in recovery from Vibrio cholerae infection","volume":"515","author":"Hsiao","year":"2014","journal-title":"Nature"},{"key":"2019101003483980700_CIT0004","volume-title":"Handbook: IMCI integrated management of childhood illnesses","year":"2005","edition":"4th"},{"key":"2019101003483980700_CIT0005","volume-title":"The treatment of diarrhea: a manual for physicians and other senior health workers","year":"2005"},{"key":"2019101003483980700_CIT0006","volume-title":"Pocket Book of Hospital Care for Children: guidelines for the management of common childhood illnesses","year":"2013","edition":"2nd"},{"key":"2019101003483980700_CIT0007","first-page":"CD008625","article-title":"Antimicrobial drugs for treating cholera","author":"Leibovici-Weissman","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2019101003483980700_CIT0008","doi-asserted-by":"crossref","first-page":"966","DOI":"10.2165\/00003495-199651060-00005","article-title":"Practical guidelines for the treatment of cholera","volume":"51","author":"Seas","year":"1996","journal-title":"Drugs"},{"key":"2019101003483980700_CIT0009","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/S1473-3099(15)00149-8","article-title":"Out-of-pocket health expenditures and antimicrobial resistance in low-income and middle-income countries: an economic analysis","volume":"15","author":"Alsan","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"2019101003483980700_CIT0010","volume-title":"Antimicrobial resistance: global report on surveillance","year":"2014"},{"key":"2019101003483980700_CIT0011","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1126\/science.aad5901","article-title":"Genomic history of the seventh pandemic of cholera in Africa","volume":"358","author":"Weill","year":"2017","journal-title":"Science"},{"key":"2019101003483980700_CIT0012","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3389\/fmicb.2015.01179","article-title":"Survey on antimicrobial resistance patterns in Vibrio vulnificus and Vibrio cholerae non-O1\/non-O139 in Germany reveals carbapenemase-producing Vibrio cholerae in coastal waters","volume":"6","author":"Bier","year":"2015","journal-title":"Front Microbiol"},{"key":"2019101003483980700_CIT0013","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fpubh.2016.00231","article-title":"Reduced Susceptibility to Extended-Spectrum \u03b2-Lactams in Vibrio cholerae Isolated in Bangladesh","volume":"4","author":"Ceccarelli","year":"2016","journal-title":"Front Public Health"},{"key":"2019101003483980700_CIT0014","doi-asserted-by":"crossref","first-page":"e0184255","DOI":"10.1371\/journal.pone.0184255","article-title":"The Vibrio cholerae var regulon encodes a metallo-\u03b2-lactamase and an antibiotic efflux pump, which are regulated by VarR, a LysR-type transcription factor","volume":"12","author":"Lin","year":"2017","journal-title":"PLoS One"},{"key":"2019101003483980700_CIT0015","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1099\/jmm.0.023051-0","article-title":"Antibiotic resistance mechanisms of Vibrio cholerae","volume":"60","author":"Kitaoka","year":"2011","journal-title":"J Med Microbiol"},{"key":"2019101003483980700_CIT0016","doi-asserted-by":"crossref","first-page":"e00381","DOI":"10.1128\/mBio.00381-15","article-title":"Gut microbial succession follows acute secretory diarrhea in humans","volume":"6","author":"David","year":"2015","journal-title":"MBio"},{"key":"2019101003483980700_CIT0017","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.etap.2014.09.011","article-title":"Determination of fluoroquinolones in chicken feces - a new liquid-liquid extraction method combined with LC-MS\/MS","volume":"38","author":"Janusch","year":"2014","journal-title":"Environ Toxicol Pharmacol"},{"key":"2019101003483980700_CIT0018","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.clinbiochem.2016.11.031","article-title":"Development and validation of a liquid chromatography tandem mass spectrometry assay for the measurement of faecal metronidazole","volume":"50","author":"Jeffery","year":"2017","journal-title":"Clin Biochem"},{"key":"2019101003483980700_CIT0019","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.5740\/jaoacint.14-040","article-title":"Method development and validation: solid Phase extraction-ultra performance liquid chromatography-tandem mass spectrometry quantification of pirlimycin in bovine feces and urine","volume":"97","author":"Ray","year":"2014","journal-title":"J AOAC Int"},{"key":"2019101003483980700_CIT0020","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/S0731-7085(98)00020-X","article-title":"A simple high performance liquid chromatography assay for simultaneous determination of omeprazole and metronidazole in human plasma and gastric fluid","volume":"17","author":"Yeung","year":"1998","journal-title":"J Pharm Biomed Anal"},{"key":"2019101003483980700_CIT0021","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1542\/peds.41.1.151","article-title":"A mail-in technique for detecting penicillin in urine: application to the study of maintenance of prophylaxis in rheumatic fever patients","volume":"41","author":"Markowitz","year":"1968","journal-title":"Pediatrics"},{"key":"2019101003483980700_CIT0022","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1097\/01.inf.0000190030.75892.78","article-title":"Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden","volume":"24","author":"Saha","year":"2005","journal-title":"Pediatr Infect Dis J"},{"key":"2019101003483980700_CIT0023","doi-asserted-by":"crossref","first-page":"e0005290","DOI":"10.1371\/journal.pntd.0005290","article-title":"Evaluation of a smartphone decision-support tool for diarrheal disease management in a resource-limited setting","volume":"11","author":"Haque","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"2019101003483980700_CIT0024","article-title":"Cholera outbreak in Netrokona Municipality, 2013","volume":"12","author":"Institute of Epidemiology, Disease Control and Research; Bangladesh Ministry of Health and Family Welfare","year":"2014","journal-title":"Health Science Bulletin"},{"key":"2019101003483980700_CIT0025","volume-title":"Manual of clinical microbiology","author":"Murray","year":"2003","edition":"8th"},{"key":"2019101003483980700_CIT0026","volume-title":"Development of a nanoliter qPCR method for gastrointestinal pathogen detection (unpublished)","author":"Grembi","year":"2019"},{"key":"2019101003483980700_CIT0027","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1128\/JCM.38.11.4145-4151.2000","article-title":"Rapid method for species-specific identification of Vibrio cholerae using primers targeted to the gene of outer membrane protein OmpW","volume":"38","author":"Nandi","year":"2000","journal-title":"J Clin Microbiol"},{"key":"2019101003483980700_CIT0028","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12915-015-0224-3","article-title":"Modulation of the human gut microbiota by dietary fibres occurs at the species level","volume":"14","author":"Chung","year":"2016","journal-title":"BMC Biol"},{"key":"2019101003483980700_CIT0029","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/AEM.03006-05","article-title":"Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB","volume":"72","author":"DeSantis","year":"2006","journal-title":"Appl Environ Microbiol"},{"key":"2019101003483980700_CIT0030","volume-title":"R: A language and environment for statistical computing","author":"R Core Team"},{"key":"2019101003483980700_CIT0031","first-page":"9","article-title":"Ondansetron metabolism and pharmacokinetics","volume":"19","author":"Pritchard","year":"1992","journal-title":"Semin Oncol"},{"key":"2019101003483980700_CIT0032","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3201\/eid1504.081214","article-title":"High prevalence of spirochetosis in cholera patients, Bangladesh","volume":"15","author":"Nelson","year":"2009","journal-title":"Emerg Infect Dis"},{"key":"2019101003483980700_CIT0033","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.00087-17","article-title":"The spirochete Brachyspira pilosicoli, enteric pathogen of animals and humans","volume":"31","author":"Hampson","year":"2018","journal-title":"Clin Microbiol Rev"},{"key":"2019101003483980700_CIT0034","doi-asserted-by":"crossref","first-page":"010402","DOI":"10.7189\/jogh.03.010402","article-title":"Diarrhea as a risk factor for acute lower respiratory tract infections among young children in low income settings","volume":"3","author":"Walker","year":"2013","journal-title":"J Glob Health"},{"key":"2019101003483980700_CIT0035","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(13)60222-6","article-title":"Global burden of childhood pneumonia and diarrhoea","volume":"381","author":"Walker","year":"2013","journal-title":"Lancet"},{"key":"2019101003483980700_CIT0036","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.pcl.2015.08.003","article-title":"Prevention and control of childhood pneumonia and diarrhea","volume":"63","author":"Leung","year":"2016","journal-title":"Pediatr Clin North Am"},{"key":"2019101003483980700_CIT0037","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1017\/S0950268811002135","article-title":"Bacterial aetiology of diarrhoeal diseases and antimicrobial resistance in Dhaka, Bangladesh, 2005\u20132008","volume":"140","author":"Ahmed","year":"2012","journal-title":"Epidemiol Infect"},{"key":"2019101003483980700_CIT0038","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1128\/AAC.01045-09","article-title":"Transferable quinolone resistance in Vibrio cholerae.","volume":"54","author":"Kim","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2019101003483980700_CIT0039","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fmicb.2017.00252","article-title":"Vibrio cholerae O1 with reduced susceptibility to ciprofloxacin and azithromycin isolated from a rural coastal area of Bangladesh","volume":"8","author":"Rashed","year":"2017","journal-title":"Front Microbiol"},{"key":"2019101003483980700_CIT0040","doi-asserted-by":"crossref","first-page":"19091","DOI":"10.1073\/pnas.0706352104","article-title":"Complexity of rice-water stool from patients with Vibrio cholerae plays a role in the transmission of infectious diarrhea","volume":"104","author":"Nelson","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019101003483980700_CIT0041","doi-asserted-by":"crossref","first-page":"e1000775","DOI":"10.1371\/journal.pgen.1000775","article-title":"Mobile antibiotic resistance encoding elements promote their own diversity","volume":"5","author":"Garriss","year":"2009","journal-title":"PLoS Genet"},{"key":"2019101003483980700_CIT0042","doi-asserted-by":"crossref","first-page":"e1000786","DOI":"10.1371\/journal.pgen.1000786","article-title":"Comparative ICE genomics: insights into the evolution of the SXT\/R391 family of ICEs","volume":"5","author":"Wozniak","year":"2009","journal-title":"PLoS Genet"},{"key":"2019101003483980700_CIT0043","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature02241","article-title":"SOS response promotes horizontal dissemination of antibiotic resistance genes","volume":"427","author":"Beaber","year":"2004","journal-title":"Nature"},{"key":"2019101003483980700_CIT0044","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/infdis\/jiy192","article-title":"Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection","volume":"218","author":"Midani","year":"2018","journal-title":"J Infect Dis"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiz299\/30054197\/jiz299.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/10\/1655\/30127350\/jiz299.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/10\/1655\/30127350\/jiz299.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T11:55:05Z","timestamp":1663674905000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/220\/10\/1655\/5515985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,6,13]]},"published-print":{"date-parts":[[2019,10,8]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiz299","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,11,15]]},"published":{"date-parts":[[2019,6,13]]}}}