{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:22:45Z","timestamp":1791325365756,"version":"4.3.1"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Clostridium difficile<\/jats:named-content>\n            causes infections of the colon in susceptible patients. Specifically, gut dysbiosis induced by treatment with broad-spectrum antibiotics facilitates germination of ingested\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            spores, expansion of vegetative cells, and production of symptom-causing toxins TcdA and TcdB. The current standard of care for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            infections (CDI) consists of administration of antibiotics such as vancomycin that target the bacterium but also perpetuate gut dysbiosis, often leading to disease recurrence. The monoclonal antitoxin antibodies actoxumab (anti-TcdA) and bezlotoxumab (anti-TcdB) are currently in development for the prevention of recurrent CDI. In this study, the effects of vancomycin or actoxumab\/bezlotoxumab treatment on progression and resolution of CDI were assessed in mice and hamsters. Rodent models of CDI are characterized by an early severe phase of symptomatic disease, associated with high rates of morbidity and mortality; high intestinal\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            burden; and a disrupted intestinal microbiota. This is followed in surviving animals by gradual recovery of the gut microbiota, associated with clearance of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            and resolution of disease symptoms over time. Treatment with vancomycin prevents disease initially by inhibiting outgrowth of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            but also delays microbiota recovery, leading to disease relapse following discontinuation of therapy. In contrast, actoxumab\/bezlotoxumab treatment does not impact the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            burden but rather prevents the appearance of toxin-dependent symptoms during the early severe phase of disease, effectively preventing disease until the microbiota (the body's natural defense against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. difficile<\/jats:named-content>\n            ) has fully recovered. These data provide insight into the mechanism of recurrence following vancomycin administration and into the mechanism of recurrence prevention observed clinically with actoxumab\/bezlotoxumab.\n          <\/jats:p>","DOI":"10.1128\/aac.00974-16","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:48:06Z","timestamp":1471308486000},"page":"6471-6482","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Disease Progression and Resolution in Rodent Models of Clostridium difficile Infection and Impact of Antitoxin Antibodies and Vancomycin"],"prefix":"10.1128","volume":"60","author":[{"given":"Peter","family":"Warn","sequence":"first","affiliation":[{"name":"Evotec (UK) Ltd., Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Thommes","sequence":"additional","affiliation":[{"name":"Evotec (UK) Ltd., Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Sattar","sequence":"additional","affiliation":[{"name":"Evotec (UK) Ltd., Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Corbett","sequence":"additional","affiliation":[{"name":"Evotec (UK) Ltd., Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Flattery","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Black","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine D.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex G.","family":"Therien","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc., Kenilworth, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.135"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0707500"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2164"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3535"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104115"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.01.011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00028"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.866515"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076269"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(09)70014-7"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i23.7416"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2002.05839.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2015.04.012"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00982-06"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907635"},{"key":"e_1_3_3_17_2","volume-title":"Abstr 55th Intersci Conf Antimicrob Agents Chemother","author":"Gerding D","year":"2015","unstructured":"Gerding D, Wilcox M, Poxton I, Kelly C, Birch T, Bouza E, Lee C, Kim YS, Yoshida J, Gabryelski L, Pedley A, Taylor A, Guris D, Kartsonis N, Dorr MB. 2015. 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