Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model
Objectives To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF. Methods The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resist...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2008-03, Vol.61 (3), p.665-669 |
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| container_title | Journal of antimicrobial chemotherapy |
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| creator | Stucki, Armin Gerber, Peter Acosta, Fernando Cottagnoud, Marianne Cottagnoud, Philippe Jiang, Lijiang Nguyen, Phong Wachtel, Derek Wang, Guoqiang Phan, Ly T. |
| description | Objectives To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF. Methods The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro. Results In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an iv injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays. Conclusions EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected. |
| doi_str_mv | 10.1093/jac/dkm505 |
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Methods The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro. Results In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an iv injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays. Conclusions EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkm505</identifier><identifier>PMID: 18222952</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Antibiotics ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Bacteria ; Bacterial diseases ; Biological and medical sciences ; Bridged-Ring Compounds - pharmacology ; Bridged-Ring Compounds - therapeutic use ; Chemotherapy ; Disease Models, Animal ; Drug resistance ; Human bacterial diseases ; Infectious diseases ; ketolide ; Macrolides - pharmacology ; Macrolides - therapeutic use ; Medical sciences ; Meningitis ; Meningitis, Bacterial - blood ; Meningitis, Bacterial - drug therapy ; Penicillin Resistance - drug effects ; Penicillin Resistance - physiology ; Penicillins - pharmacology ; Penicillins - therapeutic use ; Pharmacology. Drug treatments ; pneumococcal meningitis ; Quinolones - pharmacology ; Quinolones - therapeutic use ; Rabbits ; resistance ; Staphylococcal infections, streptococcal infections, pneumococcal infections ; Streptococcus pneumoniae ; Streptococcus pneumoniae - drug effects ; Streptococcus pneumoniae - physiology</subject><ispartof>Journal of antimicrobial chemotherapy, 2008-03, Vol.61 (3), p.665-669</ispartof><rights>The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 2008</rights><rights>2008 INIST-CNRS</rights><rights>The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-7f544980cf9fc2b2bda61255b313cc10d294c7e3c22f7c4261acf114c99e2e923</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20162954$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18222952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stucki, Armin</creatorcontrib><creatorcontrib>Gerber, Peter</creatorcontrib><creatorcontrib>Acosta, Fernando</creatorcontrib><creatorcontrib>Cottagnoud, Marianne</creatorcontrib><creatorcontrib>Cottagnoud, Philippe</creatorcontrib><creatorcontrib>Jiang, Lijiang</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Wachtel, Derek</creatorcontrib><creatorcontrib>Wang, Guoqiang</creatorcontrib><creatorcontrib>Phan, Ly T.</creatorcontrib><title>Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Objectives To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF. Methods The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro. Results In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an iv injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays. Conclusions EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected.</description><subject>Animals</subject><subject>Antibiotics</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Bacteria</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Bridged-Ring Compounds - pharmacology</subject><subject>Bridged-Ring Compounds - therapeutic use</subject><subject>Chemotherapy</subject><subject>Disease Models, Animal</subject><subject>Drug resistance</subject><subject>Human bacterial diseases</subject><subject>Infectious diseases</subject><subject>ketolide</subject><subject>Macrolides - pharmacology</subject><subject>Macrolides - therapeutic use</subject><subject>Medical sciences</subject><subject>Meningitis</subject><subject>Meningitis, Bacterial - blood</subject><subject>Meningitis, Bacterial - drug therapy</subject><subject>Penicillin Resistance - drug effects</subject><subject>Penicillin Resistance - physiology</subject><subject>Penicillins - pharmacology</subject><subject>Penicillins - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>pneumococcal meningitis</subject><subject>Quinolones - pharmacology</subject><subject>Quinolones - therapeutic use</subject><subject>Rabbits</subject><subject>resistance</subject><subject>Staphylococcal infections, streptococcal infections, pneumococcal infections</subject><subject>Streptococcus pneumoniae</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Streptococcus pneumoniae - physiology</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0U1rFDEYwPFBFLutXvwAEgR7EMbmPZujtlsrFPRQUbyEzDOJZjuTTJMZ0IPf3eguLYjoKQR-PA_Jv2meEPySYM1OthZO-utRYHGvWREucUuxJvebFWZYtIoLdtAclrLFGEsh1w-bA7KmlGpBV82PjfcO5oKSR5uz9y2nGKWIJhcDhGEIsc2uhDLbOCMbe3SzhJiGFF37-_pXN0W3jAkSQEAhovmrQ9l2XZjRWHn8EuZQ0Jh6NzxqHng7FPd4fx41H843V6cX7eW7N29PX122wJWaW-UF53qNwWsPtKNdbyWhQnSMMACCe6o5KMeAUq-AU0kseEI4aO2o05QdNce7uVNON4srsxlDATcMNrq0FKPqT3Es8X8hxYIJiXmFz_6A27TkWB9hKFFSqrXSFb3YIciplOy8mXIYbf5uCDa_0pmazuzSVfx0P3HpRtff0X2rCp7vgS1gB59thFBuHcVEVsfvXFqmfy9sd65mc99upc3XRiqmhLn49Nl8pJjr1-dn5or9BKDivY8</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>Stucki, Armin</creator><creator>Gerber, Peter</creator><creator>Acosta, Fernando</creator><creator>Cottagnoud, Marianne</creator><creator>Cottagnoud, Philippe</creator><creator>Jiang, Lijiang</creator><creator>Nguyen, Phong</creator><creator>Wachtel, Derek</creator><creator>Wang, Guoqiang</creator><creator>Phan, Ly T.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20080301</creationdate><title>Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model</title><author>Stucki, Armin ; Gerber, Peter ; Acosta, Fernando ; Cottagnoud, Marianne ; Cottagnoud, Philippe ; Jiang, Lijiang ; Nguyen, Phong ; Wachtel, Derek ; Wang, Guoqiang ; Phan, Ly T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-7f544980cf9fc2b2bda61255b313cc10d294c7e3c22f7c4261acf114c99e2e923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antibiotics</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Bacteria</topic><topic>Bacterial diseases</topic><topic>Biological and medical sciences</topic><topic>Bridged-Ring Compounds - pharmacology</topic><topic>Bridged-Ring Compounds - therapeutic use</topic><topic>Chemotherapy</topic><topic>Disease Models, Animal</topic><topic>Drug resistance</topic><topic>Human bacterial diseases</topic><topic>Infectious diseases</topic><topic>ketolide</topic><topic>Macrolides - pharmacology</topic><topic>Macrolides - therapeutic use</topic><topic>Medical sciences</topic><topic>Meningitis</topic><topic>Meningitis, Bacterial - blood</topic><topic>Meningitis, Bacterial - drug therapy</topic><topic>Penicillin Resistance - drug effects</topic><topic>Penicillin Resistance - physiology</topic><topic>Penicillins - pharmacology</topic><topic>Penicillins - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>pneumococcal meningitis</topic><topic>Quinolones - pharmacology</topic><topic>Quinolones - therapeutic use</topic><topic>Rabbits</topic><topic>resistance</topic><topic>Staphylococcal infections, streptococcal infections, pneumococcal infections</topic><topic>Streptococcus pneumoniae</topic><topic>Streptococcus pneumoniae - drug effects</topic><topic>Streptococcus pneumoniae - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stucki, Armin</creatorcontrib><creatorcontrib>Gerber, Peter</creatorcontrib><creatorcontrib>Acosta, Fernando</creatorcontrib><creatorcontrib>Cottagnoud, Marianne</creatorcontrib><creatorcontrib>Cottagnoud, Philippe</creatorcontrib><creatorcontrib>Jiang, Lijiang</creatorcontrib><creatorcontrib>Nguyen, Phong</creatorcontrib><creatorcontrib>Wachtel, Derek</creatorcontrib><creatorcontrib>Wang, Guoqiang</creatorcontrib><creatorcontrib>Phan, Ly T.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stucki, Armin</au><au>Gerber, Peter</au><au>Acosta, Fernando</au><au>Cottagnoud, Marianne</au><au>Cottagnoud, Philippe</au><au>Jiang, Lijiang</au><au>Nguyen, Phong</au><au>Wachtel, Derek</au><au>Wang, Guoqiang</au><au>Phan, Ly T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>61</volume><issue>3</issue><spage>665</spage><epage>669</epage><pages>665-669</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><coden>JACHDX</coden><abstract>Objectives To test the efficacy of EDP-420, a new ketolide, in experimental pneumococcal meningitis and to determine its penetration into the CSF. Methods The experimental rabbit model was used in this study and EDP-420 was tested against a penicillin-resistant and a penicillin- and quinolone-resistant mutant. EDP-420 was also tested against both strains in time-killing assays over 8 h in vitro. Results In experimental meningitis, EDP-420 produced a bactericidal activity comparable to the standard regimen based on a combination of vancomycin with ceftriaxone against a penicillin-resistant Streptococcus pneumoniae and a penicillin- and quinolone-resistant S. pneumoniae isolate. The penetration of EDP-420 into inflamed meninges was 38% after an iv injection of 10 mg/kg. The bactericidal activity of EDP-420 was also confirmed in in vitro time-killing assays. Conclusions EDP-420 is an efficacious alternative treatment in pneumococcal meningitis, especially when resistant strains are suspected.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>18222952</pmid><doi>10.1093/jac/dkm505</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Antibiotics Antibiotics. Antiinfectious agents. Antiparasitic agents Bacteria Bacterial diseases Biological and medical sciences Bridged-Ring Compounds - pharmacology Bridged-Ring Compounds - therapeutic use Chemotherapy Disease Models, Animal Drug resistance Human bacterial diseases Infectious diseases ketolide Macrolides - pharmacology Macrolides - therapeutic use Medical sciences Meningitis Meningitis, Bacterial - blood Meningitis, Bacterial - drug therapy Penicillin Resistance - drug effects Penicillin Resistance - physiology Penicillins - pharmacology Penicillins - therapeutic use Pharmacology. Drug treatments pneumococcal meningitis Quinolones - pharmacology Quinolones - therapeutic use Rabbits resistance Staphylococcal infections, streptococcal infections, pneumococcal infections Streptococcus pneumoniae Streptococcus pneumoniae - drug effects Streptococcus pneumoniae - physiology |
| title | Effects of EDP-420 on penicillin-resistant and quinolone- and penicillin-resistant pneumococci in the rabbit meningitis model |
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