{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:32:24Z","timestamp":1790681544776,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>DAV132 (colon-targeted adsorbent) has prevented antibiotic-induced effects on microbiota in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess DAV132 safety and biological efficacy in patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>An open-label, randomized [stratification: fluoroquinolone (FQ) indication] multicentre trial comparing DAV132 (7.5\u2009g, 3 times a day, orally) with No-DAV132 in hospitalized patients requiring 5\u201321\u2009day treatment with FQs and at risk of Clostridioides difficile infection (CDI). FQ and DAV132 were started simultaneously, DAV132 was administered for 48\u2009h more, and patients were followed up for 51\u2009days. The primary endpoint was the rate of adverse events (AEs) independently adjudicated as related to DAV132 and\/or FQ. The planned sample size of 260 patients would provide a 95% CI of \u00b111.4%, assuming a 33% treatment-related AE rate. Plasma and faecal FQ concentrations, intestinal microbiota diversity, intestinal colonization with C. difficile, MDR bacteria and yeasts, and ex vivo resistance to C. difficile faecal colonization were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two hundred and forty-three patients (median age 71\u2009years; 96% with chronic comorbidity) were included (No-DAV132, n = 120; DAV132, n = 123). DAV132- and\/or FQ-related AEs did not differ significantly: 18 (14.8%) versus 13 (10.8%) in DAV132 versus No-DAV132 patients (difference 3.9%; 95% CI: \u22124.7 to 12.6). Day 4 FQ plasma levels were unaffected. DAV132 was associated with a &amp;gt;98% reduction in faecal FQ levels (Day 4 to end of treatment; P &amp;lt; 0.001), less impaired microbiota diversity (Shannon index; P = 0.003), increased ex vivo resistance to C. difficile colonization (P = 0.0003) and less frequent FQ-induced VRE acquisition (P = 0.01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In FQ-treated hospitalized patients, DAV132 was well tolerated, and FQ plasma concentrations unaffected. DAV132 preserved intestinal microbiota diversity and C. difficile colonization resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkab474","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T15:12:19Z","timestamp":1639062739000},"page":"1155-1165","source":"Crossref","is-referenced-by-count":47,"title":["An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones"],"prefix":"10.1093","volume":"77","author":[{"given":"Maria J. G. T.","family":"Vehreschild","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Ducher","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Louie","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine, University of Calgary, Calgary, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver A.","family":"Cornely","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University of Cologne, Cologne, Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany"},{"name":"Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS K\u00f6ln), University of Cologne, Cologne, Germany"},{"name":"German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Feger","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"},{"name":"EMIBiotech, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Dane","sequence":"additional","affiliation":[{"name":"Danestat, Macclesfield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Varastet","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Vitry","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"de Gunzburg","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Andremont","sequence":"additional","affiliation":[{"name":"Da Volterra, Paris, France"},{"name":"Universit\u00e9 de Paris, IAME, INSERM U1137, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Mentr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, INSERM U1137, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4565-2868","authenticated-orcid":false,"given":"Mark H.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"Leeds Institute of Medical Research, University of Leeds and Leeds Teaching Hospitals, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"2022033111264414100_dkab474-B1","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1099\/mic.0.040618-0","article-title":"Long-term impacts of antibiotic exposure on the human intestinal microbiota","volume":"156","author":"Jernberg","year":"2010","journal-title":"Microbiology"},{"issue":"Suppl 1","key":"2022033111264414100_dkab474-B2","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1073\/pnas.1000087107","article-title":"Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation","volume":"108","author":"Dethlefsen","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022033111264414100_dkab474-B3","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1136\/gutjnl-2012-303184","article-title":"Gut microbiota disturbance during antibiotic therapy: a multi-omic approach","volume":"62","author":"P\u00e9rez-Cobas","year":"2013","journal-title":"Gut"},{"key":"2022033111264414100_dkab474-B4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"2022033111264414100_dkab474-B5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nrendo.2014.210","article-title":"Antibiotics in early life and obesity","volume":"11","author":"Cox","year":"2015","journal-title":"Nat Rev Endocrinol"},{"key":"2022033111264414100_dkab474-B6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.mayocp.2020.07.019","article-title":"Association of infant antibiotic exposure with childhood health outcomes","volume":"96","author":"Aversa","year":"2021","journal-title":"Mayo Clin Proc"},{"key":"2022033111264414100_dkab474-B7","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1128\/AAC.00823-10","article-title":"Independent behavior of commensal flora for carriage of fluoroquinolone-resistant bacteria in patients at admission","volume":"54","author":"de Lastours","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111264414100_dkab474-B8","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3390\/genes6041347","article-title":"Disruption of the gut microbiome: Clostridium difficile infection and the threat of antibiotic resistance","volume":"6","author":"Johanesen","year":"2015","journal-title":"Genes"},{"key":"2022033111264414100_dkab474-B9","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1056\/NEJMra1403772","article-title":"Clostridium difficile infection","volume":"372","author":"Leffler","year":"2015","journal-title":"N Engl J Med"},{"key":"2022033111264414100_dkab474-B10","doi-asserted-by":"crossref","first-page":"339ra71","DOI":"10.1126\/scitranslmed.aaf2311","article-title":"Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice","volume":"8","author":"Shono","year":"2016","journal-title":"Sci Transl Med"},{"key":"2022033111264414100_dkab474-B11","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1056\/NEJMoa1900623","article-title":"Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation","volume":"382","author":"Peled","year":"2020","journal-title":"N Engl J Med"},{"key":"2022033111264414100_dkab474-B12","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1016\/j.drudis.2021.02.022","article-title":"Spare and repair the gut microbiota from antibiotic-induced dysbiosis: state-of-the-art","volume":"26","author":"Andremont","year":"2021","journal-title":"Drug Discov Today"},{"key":"2022033111264414100_dkab474-B13","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/infdis\/160.2.274","article-title":"Use of beta-lactamase-producing anaerobes to prevent ceftriaxone from degrading intestinal resistance to colonization","volume":"160","author":"Leonard","year":"1989","journal-title":"J Infect Dis"},{"key":"2022033111264414100_dkab474-B14","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1086\/379153","article-title":"Oral administration of \u03b2-lactamase preserves colonization resistance of piperacillin-treated mice","volume":"188","author":"Stiefel","year":"2003","journal-title":"J Infect Dis"},{"key":"2022033111264414100_dkab474-B15","first-page":"838","article-title":"IPSAT P1A, a class A \u03b2-lactamase therapy for the prevention of penicillin-induced disruption to the intestinal microflora","volume":"10","author":"Pitout","year":"2009","journal-title":"Curr Opin Investig Drugs"},{"key":"2022033111264414100_dkab474-B16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/jam.13432","article-title":"SYN-004 (ribaxamase), an oral \u03b2-lactamase, mitigates antibiotic-mediated dysbiosis in a porcine gut microbiome model","volume":"123","author":"Connelly","year":"2017","journal-title":"J Appl Microbiol"},{"key":"2022033111264414100_dkab474-B17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S1473-3099(18)30731-X","article-title":"Use of ribaxamase (SYN-004), a \u03b2-lactamase, to prevent Clostridium difficile infection in \u03b2-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial","volume":"19","author":"Kokai-Kun","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2022033111264414100_dkab474-B18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/jcph.359","article-title":"Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: a proof of concept study in healthy subject","volume":"55","author":"de Gunzburg","year":"2015","journal-title":"J Clin Pharmacol"},{"key":"2022033111264414100_dkab474-B19","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/infdis\/jix604","article-title":"Protection of the human gut microbiome from antibiotics","volume":"217","author":"de Gunzburg","year":"2018","journal-title":"J Infect Dis"},{"key":"2022033111264414100_dkab474-B20","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/cpdd.901","article-title":"A colon-targeted adsorbent (DAV132) does not affect the pharmacokinetics of warfarin or clonazepam in healthy subjects","volume":"10","author":"Pinquier","year":"2021","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"Suppl 4","key":"2022033111264414100_dkab474-B21","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1016\/j.cmi.2016.03.010","article-title":"European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection","volume":"22","author":"Crobach","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"2022033111264414100_dkab474-B22","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/S0140-6736(13)61218-0","article-title":"Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial","volume":"382","author":"Allen","year":"2013","journal-title":"Lancet"},{"key":"2022033111264414100_dkab474-B23","doi-asserted-by":"crossref","first-page":"e00925-18","DOI":"10.1128\/AAC.00925-18","article-title":"Antibiotic-induced dysbiosis predicts mortality in an animal model of Clostridium difficile infection","volume":"62","author":"Burdet","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111264414100_dkab474-B24","doi-asserted-by":"crossref","first-page":"e01401-20","DOI":"10.1128\/AAC.01401-20","article-title":"Optimization of an assay to determine colonization resistance to Clostridioides difficile in fecal samples from healthy subjects and those treated with antibiotics","volume":"65","author":"Harris","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111264414100_dkab474-B25","author":"R Core Team","year":"2020"},{"key":"2022033111264414100_dkab474-B26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"2022033111264414100_dkab474-B27","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.copbio.2012.08.005","article-title":"Bacteria as vitamin suppliers to their host: a gut microbiota perspective","volume":"24","author":"LeBlanc","year":"2013","journal-title":"Curr Opin Biotechnol"},{"key":"2022033111264414100_dkab474-B28","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.4014\/jmb.1709.09027","article-title":"Deciphering diversity indices for a better understanding of microbial communities","volume":"27","author":"Kim","year":"2017","journal-title":"J Microbiol Biotechnol"},{"key":"2022033111264414100_dkab474-B29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s15010-012-0269-y","article-title":"Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum \u03b2-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies","volume":"40","author":"Liss","year":"2012","journal-title":"Infection"},{"key":"2022033111264414100_dkab474-B30","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00134-018-5268-8","article-title":"Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection","volume":"44","author":"Freedberg","year":"2018","journal-title":"Intensive Care Med"},{"key":"2022033111264414100_dkab474-B31","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1056\/NEJM200012283432604","article-title":"Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients","volume":"343","author":"Donskey","year":"2000","journal-title":"N Engl J Med"},{"key":"2022033111264414100_dkab474-B32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jhin.2007.06.009","article-title":"Rapid control of an outbreak of vancomycin-resistant enterococci in a French university hospital","volume":"67","author":"Lucet","year":"2007","journal-title":"J Hosp Infect"},{"key":"2022033111264414100_dkab474-B33","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1128\/AAC.00039-13","article-title":"Oral DAV131, a charcoal-based adsorbent, inhibits intestinal colonization by \u03b2-lactam-resistant Klebsiella pneumoniae in cefotaxime-treated mice","volume":"57","author":"Grall","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111264414100_dkab474-B34","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.cmi.2018.12.009","article-title":"A 5-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae: a randomized clinical trial","volume":"25","author":"Huttner","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2022033111264414100_dkab474-B35","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jinf.2020.09.003","article-title":"Fecal microbiota transplantation for multidrug-resistant organism: efficacy and response prediction","volume":"81","author":"Seong","year":"2020","journal-title":"J Infect"},{"key":"2022033111264414100_dkab474-B36","doi-asserted-by":"crossref","first-page":"ofw133","DOI":"10.1093\/ofid\/ofw133","article-title":"Clearance of vancomycin-resistant Enterococcus concomitant with administration of a microbiota-based drug targeted at recurrent Clostridium difficile infection","volume":"3","author":"Dubberke","year":"2016","journal-title":"Open Forum Infect Dis"},{"key":"2022033111264414100_dkab474-B37","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.cmi.2019.03.025","article-title":"Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract","volume":"25","author":"Kuijper","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2022033111264414100_dkab474-B38","doi-asserted-by":"crossref","first-page":"e00543-17","DOI":"10.1128\/AAC.00543-17","article-title":"Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with DAV131A in a model of moxifloxacin-induced Clostridium difficile colitis","volume":"61","author":"Burdet","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2022033111264414100_dkab474-B39","doi-asserted-by":"crossref","first-page":"e01196-19","DOI":"10.1128\/AAC.01196-19","article-title":"DAV131A protects hamsters from lethal Clostridioides difficile infection induced by fluoroquinolones","volume":"64","author":"Saint-Lu","year":"2019","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/4\/1155\/43192676\/dkab474.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/77\/4\/1155\/43192676\/dkab474.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:02:29Z","timestamp":1726272149000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/77\/4\/1155\/6500724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,7]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,1,7]]},"published-print":{"date-parts":[[2022,3,31]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab474","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,4,1]]},"published":{"date-parts":[[2022,1,7]]}}}