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Discovery and development of surotomycin for the treatment of Clostridium difficile
The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in...
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| Published in: | Journal of Industrial Microbiology & Biotechnology 2016-03, Vol.43 (2-3), p.195-204 |
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| container_issue | 2-3 |
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| container_title | Journal of Industrial Microbiology & Biotechnology |
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| creator | Knight-Connoni, Victoria Mascio, Carmela Chesnel, Laurent Silverman, Jared |
| description | The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin. |
| doi_str_mv | 10.1007/s10295-015-1714-6 |
| format | article |
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Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin.</description><identifier>ISSN: 1367-5435</identifier><identifier>EISSN: 1476-5535</identifier><identifier>DOI: 10.1007/s10295-015-1714-6</identifier><identifier>PMID: 26670919</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>anaerobes ; animal models ; Animals ; Anti-Bacterial Agents - isolation & purification ; Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Antimicrobial agents ; Bacterial infections ; Bioavailability ; Biochemistry ; Bioinformatics ; Biological Availability ; Biomedical and Life Sciences ; Biomedical research ; Biotechnology ; cell membranes ; Clinical Trials, Phase II as Topic ; Clostridium difficile ; Clostridium difficile - cytology ; Clostridium difficile - drug effects ; Clostridium Infections - drug therapy ; Clostridium Infections - microbiology ; Diarrhea ; Feces ; Fermentation ; Gastrointestinal diseases ; Gastrointestinal Microbiome - drug effects ; gastrointestinal system ; Gastrointestinal tract ; Genetic Engineering ; Humans ; Infections ; Inorganic Chemistry ; Laboratories ; Life Sciences ; lipopeptides ; Lipopeptides - administration & dosage ; Lipopeptides - isolation & purification ; Lipopeptides - pharmacokinetics ; Lipopeptides - pharmacology ; Lipopeptides - therapeutic use ; Microbial Sensitivity Tests ; Microbiology ; Microbiota ; microorganisms ; minimum inhibitory concentration ; Natural products ; patients ; Peptides ; Peptides, Cyclic - administration & dosage ; Peptides, Cyclic - isolation & purification ; Peptides, Cyclic - pharmacokinetics ; Peptides, Cyclic - pharmacology ; Peptides, Cyclic - therapeutic use ; relapse ; Review ; Streptomyces ; Streptomyces roseosporus ; Studies ; vancomycin</subject><ispartof>Journal of Industrial Microbiology & Biotechnology, 2016-03, Vol.43 (2-3), p.195-204</ispartof><rights>Society for Industrial Microbiology and Biotechnology 2015</rights><rights>Society for Industrial Microbiology and Biotechnology 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-8fa2c6be2e48c82342270fe1e97a3ab2111d72c87e0353bdccbb4305c38437e33</citedby><cites>FETCH-LOGICAL-c579t-8fa2c6be2e48c82342270fe1e97a3ab2111d72c87e0353bdccbb4305c38437e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1764833365/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1764833365?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>313,314,780,784,792,11688,27922,27924,27925,36060,36061,44363,74895</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26670919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Knight-Connoni, Victoria</creatorcontrib><creatorcontrib>Mascio, Carmela</creatorcontrib><creatorcontrib>Chesnel, Laurent</creatorcontrib><creatorcontrib>Silverman, Jared</creatorcontrib><title>Discovery and development of surotomycin for the treatment of Clostridium difficile</title><title>Journal of Industrial Microbiology & Biotechnology</title><addtitle>J Ind Microbiol Biotechnol</addtitle><addtitle>J Ind Microbiol Biotechnol</addtitle><description>The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin.</description><subject>anaerobes</subject><subject>animal models</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - isolation & purification</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Bacterial infections</subject><subject>Bioavailability</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biological Availability</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical research</subject><subject>Biotechnology</subject><subject>cell membranes</subject><subject>Clinical Trials, Phase II as Topic</subject><subject>Clostridium difficile</subject><subject>Clostridium difficile - cytology</subject><subject>Clostridium difficile - 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Academic</collection><collection>Biotechnology Research Abstracts</collection><jtitle>Journal of Industrial Microbiology & Biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Knight-Connoni, Victoria</au><au>Mascio, Carmela</au><au>Chesnel, Laurent</au><au>Silverman, Jared</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery and development of surotomycin for the treatment of Clostridium difficile</atitle><jtitle>Journal of Industrial Microbiology & Biotechnology</jtitle><stitle>J Ind Microbiol Biotechnol</stitle><addtitle>J Ind Microbiol Biotechnol</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>43</volume><issue>2-3</issue><spage>195</spage><epage>204</epage><pages>195-204</pages><issn>1367-5435</issn><eissn>1476-5535</eissn><abstract>The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26670919</pmid><doi>10.1007/s10295-015-1714-6</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of Industrial Microbiology & Biotechnology, 2016-03, Vol.43 (2-3), p.195-204 |
| issn | 1367-5435 1476-5535 |
| language | eng |
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| source | ABI/INFORM global; Open Access: Oxford University Press Open Journals |
| subjects | anaerobes animal models Animals Anti-Bacterial Agents - isolation & purification Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Antibiotics Antimicrobial agents Bacterial infections Bioavailability Biochemistry Bioinformatics Biological Availability Biomedical and Life Sciences Biomedical research Biotechnology cell membranes Clinical Trials, Phase II as Topic Clostridium difficile Clostridium difficile - cytology Clostridium difficile - drug effects Clostridium Infections - drug therapy Clostridium Infections - microbiology Diarrhea Feces Fermentation Gastrointestinal diseases Gastrointestinal Microbiome - drug effects gastrointestinal system Gastrointestinal tract Genetic Engineering Humans Infections Inorganic Chemistry Laboratories Life Sciences lipopeptides Lipopeptides - administration & dosage Lipopeptides - isolation & purification Lipopeptides - pharmacokinetics Lipopeptides - pharmacology Lipopeptides - therapeutic use Microbial Sensitivity Tests Microbiology Microbiota microorganisms minimum inhibitory concentration Natural products patients Peptides Peptides, Cyclic - administration & dosage Peptides, Cyclic - isolation & purification Peptides, Cyclic - pharmacokinetics Peptides, Cyclic - pharmacology Peptides, Cyclic - therapeutic use relapse Review Streptomyces Streptomyces roseosporus Studies vancomycin |
| title | Discovery and development of surotomycin for the treatment of Clostridium difficile |
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