{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:32:44Z","timestamp":1787016764524,"version":"build-2736575974"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"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":[[2014,8]]},"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                    infection (CDI) is a common, debilitating infection with high morbidity and mortality.\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                    causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters\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                    toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 \u03bcM), and after 30 min, the loops were injected with purified\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                    toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements.\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                    toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1\u03b2 (IL-1\u03b2) protein and mRNA expression. Treatment with fidaxomicin (20 \u03bcM) or its primary metabolite, OP-1118 (120 \u03bcM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1\u03b2 protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 \u03bcM) and metronidazole (20 \u03bcM) did not alter toxin A-induced histologic damage and IL-1\u03b2 protein expression. In addition to its well known antibacterial effects 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                    , fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects 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                    toxins.\n                  <\/jats:p>","DOI":"10.1128\/aac.02783-14","type":"journal-article","created":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T02:12:01Z","timestamp":1401761521000},"page":"4642-4650","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum"],"prefix":"10.1128","volume":"58","author":[{"given":"Hon Wai","family":"Koon","sequence":"first","affiliation":[{"name":"Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Ho","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tressia C.","family":"Hing","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Cubist Pharmaceuticals, Inc., Lexington, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciar\u00e1n P.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalabos","family":"Pothoulakis","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0707500"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09397"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.03.016"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2009.03.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70374-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis499"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0910812"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06305-11"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00625-11"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01623-06"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis358"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks450"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2165\/11208220-000000000-00000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-52"},{"key":"e_1_3_2_16_2","first-page":"153","article-title":"Azithromycin reduces inflammation in a rat model of acute conjunctivitis","volume":"19","author":"Fernandez-Robredo P","year":"2013","unstructured":"Fernandez-RobredoPRecaldeSMoreno-OrdunaMGarcia-GarciaLZarranz-VenturaJGarcia-LayanaA. 2013. 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