Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus
Abstract Background Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2019-01, Vol.74 (1), p.82-86 |
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| creator | Xhemali, Xhilda Smith, Jordan R Kebriaei, Razieh Rice, Seth A Stamper, Kyle C Compton, Matthew Singh, Nivedita B Jahanbakhsh, Seyedehameneh Rybak, Michael J |
| description | Abstract
Background
Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and time–kill assays against resistant phenotypes of Staphylococcus aureus.
Methods
S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five β-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each β-lactam to determine the effect of each β-lactam on dalbavancin MIC. Time–kill assays were performed with dalbavancin and β-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time–kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time.
Results
Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each β-lactam. In time–kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains.
Conclusions
Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with β-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted. |
| doi_str_mv | 10.1093/jac/dky376 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2113277071</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/jac/dky376</oup_id><sourcerecordid>2113277071</sourcerecordid><originalsourceid>FETCH-LOGICAL-c353t-61746858b7bcbb8c7a8a89dc7d040b7ffe7c3883b273e3a7929d005f2d641b343</originalsourceid><addsrcrecordid>eNp90MtKxDAUBuAgijNeNj6AZCOIUE2atmmXMniDARfqupykqRNtk9qkSte-kQ_iM5mho0tXh8P5-OH8CB1Rck5JwS5eQF5UryPj2Raa0yQjUUwKuo3mhJE04knKZmjPuRdCSJZm-S6aMRJnJCHFHH1evUMzgNfWYFvjChoB72CkNhgaaxQGU-GwSNsKbSb3of0Kf39FDUgPbRBeC229lg7DM2jjPO6V086HC-5Wylg_dsqt8x88dKuxsdJKOQQ-9GpwB2inhsapw83cR0_XV4-L22h5f3O3uFxGkqXMRxnlSZanueBCCpFLDjnkRSV5FV4RvK4VlyzPmYg5Uwx4ERcVIWkdV1lCBUvYPjqdcrvevg3K-bLVTqqmAaPs4MqYUhZzTjgN9GyisrfO9aouu1630I8lJeW69DKUXk6lB3y8yR1Eq6o_-ttyACcTsEP3X9APRYSOPA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2113277071</pqid></control><display><type>article</type><title>Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Xhemali, Xhilda ; Smith, Jordan R ; Kebriaei, Razieh ; Rice, Seth A ; Stamper, Kyle C ; Compton, Matthew ; Singh, Nivedita B ; Jahanbakhsh, Seyedehameneh ; Rybak, Michael J</creator><creatorcontrib>Xhemali, Xhilda ; Smith, Jordan R ; Kebriaei, Razieh ; Rice, Seth A ; Stamper, Kyle C ; Compton, Matthew ; Singh, Nivedita B ; Jahanbakhsh, Seyedehameneh ; Rybak, Michael J</creatorcontrib><description>Abstract
Background
Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and time–kill assays against resistant phenotypes of Staphylococcus aureus.
Methods
S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five β-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each β-lactam to determine the effect of each β-lactam on dalbavancin MIC. Time–kill assays were performed with dalbavancin and β-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time–kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time.
Results
Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each β-lactam. In time–kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains.
Conclusions
Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with β-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dky376</identifier><identifier>PMID: 30260409</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Anti-Bacterial Agents - pharmacology ; beta-Lactams - pharmacology ; Drug Interactions ; Drug Resistance, Bacterial - drug effects ; Microbial Sensitivity Tests ; Phenotype ; Staphylococcus aureus - drug effects ; Teicoplanin - analogs & derivatives ; Teicoplanin - pharmacology</subject><ispartof>Journal of antimicrobial chemotherapy, 2019-01, Vol.74 (1), p.82-86</ispartof><rights>The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-61746858b7bcbb8c7a8a89dc7d040b7ffe7c3883b273e3a7929d005f2d641b343</citedby><cites>FETCH-LOGICAL-c353t-61746858b7bcbb8c7a8a89dc7d040b7ffe7c3883b273e3a7929d005f2d641b343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30260409$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xhemali, Xhilda</creatorcontrib><creatorcontrib>Smith, Jordan R</creatorcontrib><creatorcontrib>Kebriaei, Razieh</creatorcontrib><creatorcontrib>Rice, Seth A</creatorcontrib><creatorcontrib>Stamper, Kyle C</creatorcontrib><creatorcontrib>Compton, Matthew</creatorcontrib><creatorcontrib>Singh, Nivedita B</creatorcontrib><creatorcontrib>Jahanbakhsh, Seyedehameneh</creatorcontrib><creatorcontrib>Rybak, Michael J</creatorcontrib><title>Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Background
Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and time–kill assays against resistant phenotypes of Staphylococcus aureus.
Methods
S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five β-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each β-lactam to determine the effect of each β-lactam on dalbavancin MIC. Time–kill assays were performed with dalbavancin and β-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time–kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time.
Results
Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each β-lactam. In time–kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains.
Conclusions
Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with β-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>beta-Lactams - pharmacology</subject><subject>Drug Interactions</subject><subject>Drug Resistance, Bacterial - drug effects</subject><subject>Microbial Sensitivity Tests</subject><subject>Phenotype</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Teicoplanin - analogs & derivatives</subject><subject>Teicoplanin - pharmacology</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90MtKxDAUBuAgijNeNj6AZCOIUE2atmmXMniDARfqupykqRNtk9qkSte-kQ_iM5mho0tXh8P5-OH8CB1Rck5JwS5eQF5UryPj2Raa0yQjUUwKuo3mhJE04knKZmjPuRdCSJZm-S6aMRJnJCHFHH1evUMzgNfWYFvjChoB72CkNhgaaxQGU-GwSNsKbSb3of0Kf39FDUgPbRBeC229lg7DM2jjPO6V086HC-5Wylg_dsqt8x88dKuxsdJKOQQ-9GpwB2inhsapw83cR0_XV4-L22h5f3O3uFxGkqXMRxnlSZanueBCCpFLDjnkRSV5FV4RvK4VlyzPmYg5Uwx4ERcVIWkdV1lCBUvYPjqdcrvevg3K-bLVTqqmAaPs4MqYUhZzTjgN9GyisrfO9aouu1630I8lJeW69DKUXk6lB3y8yR1Eq6o_-ttyACcTsEP3X9APRYSOPA</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Xhemali, Xhilda</creator><creator>Smith, Jordan R</creator><creator>Kebriaei, Razieh</creator><creator>Rice, Seth A</creator><creator>Stamper, Kyle C</creator><creator>Compton, Matthew</creator><creator>Singh, Nivedita B</creator><creator>Jahanbakhsh, Seyedehameneh</creator><creator>Rybak, Michael J</creator><general>Oxford University Press</general><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>7X8</scope></search><sort><creationdate>20190101</creationdate><title>Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus</title><author>Xhemali, Xhilda ; Smith, Jordan R ; Kebriaei, Razieh ; Rice, Seth A ; Stamper, Kyle C ; Compton, Matthew ; Singh, Nivedita B ; Jahanbakhsh, Seyedehameneh ; Rybak, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-61746858b7bcbb8c7a8a89dc7d040b7ffe7c3883b273e3a7929d005f2d641b343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>beta-Lactams - pharmacology</topic><topic>Drug Interactions</topic><topic>Drug Resistance, Bacterial - drug effects</topic><topic>Microbial Sensitivity Tests</topic><topic>Phenotype</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Teicoplanin - analogs & derivatives</topic><topic>Teicoplanin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xhemali, Xhilda</creatorcontrib><creatorcontrib>Smith, Jordan R</creatorcontrib><creatorcontrib>Kebriaei, Razieh</creatorcontrib><creatorcontrib>Rice, Seth A</creatorcontrib><creatorcontrib>Stamper, Kyle C</creatorcontrib><creatorcontrib>Compton, Matthew</creatorcontrib><creatorcontrib>Singh, Nivedita B</creatorcontrib><creatorcontrib>Jahanbakhsh, Seyedehameneh</creatorcontrib><creatorcontrib>Rybak, Michael J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xhemali, Xhilda</au><au>Smith, Jordan R</au><au>Kebriaei, Razieh</au><au>Rice, Seth A</au><au>Stamper, Kyle C</au><au>Compton, Matthew</au><au>Singh, Nivedita B</au><au>Jahanbakhsh, Seyedehameneh</au><au>Rybak, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>74</volume><issue>1</issue><spage>82</spage><epage>86</epage><pages>82-86</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Background
Emergence of reduced susceptibility to vancomycin warrants the development of new antimicrobial agents for the treatment of MRSA. We evaluated the activity of dalbavancin, a novel lipoglycopeptide antibiotic, both alone and combined with β-lactams, in combination MIC testing and time–kill assays against resistant phenotypes of Staphylococcus aureus.
Methods
S. aureus isolates included 50 organisms with varying susceptibility patterns. Dalbavancin was tested alone and in combination with five β-lactams: cefazolin, cefepime, ceftaroline, ertapenem and oxacillin. MIC values of the antibiotics were determined for all isolates. After initial MIC testing, dalbavancin MICs were determined in the presence of 0.5 × MIC of each β-lactam to determine the effect of each β-lactam on dalbavancin MIC. Time–kill assays were performed with dalbavancin and β-lactams tested at 0.5 × MIC for randomly selected organisms representing each MRSA phenotype. Time–kill curves were generated by plotting mean colony counts (log10 cfu/mL) versus time.
Results
Dalbavancin MIC50 was 0.0313 mg/L and MIC90 was 0.0625 mg/L. Dalbavancin MICs decreased by zero to greater than five 2-fold dilutions in combination with each β-lactam. In time–kill assays, dalbavancin was synergistic with cefazolin, cefepime and ertapenem against all strains and the combination of dalbavancin and ceftaroline was synergistic against all but one. The combination of dalbavancin and oxacillin was synergistic against 5/8 strains.
Conclusions
Dalbavancin was active against all MRSA strains tested, including heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, daptomycin-non-susceptible and linezolid-resistant isolates. The synergy demonstrated against these organisms supports the use of dalbavancin in combination with β-lactams against resistant phenotypes of S. aureus. Further evaluation is warranted.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>30260409</pmid><doi>10.1093/jac/dky376</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antimicrobial chemotherapy, 2019-01, Vol.74 (1), p.82-86 |
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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 | Anti-Bacterial Agents - pharmacology beta-Lactams - pharmacology Drug Interactions Drug Resistance, Bacterial - drug effects Microbial Sensitivity Tests Phenotype Staphylococcus aureus - drug effects Teicoplanin - analogs & derivatives Teicoplanin - pharmacology |
| title | Evaluation of dalbavancin alone and in combination with β-lactam antibiotics against resistant phenotypes of Staphylococcus aureus |
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