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Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization
To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR). Susceptibility testing by broth microdilution was performed on 30 MRSA...
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| Published in: | Journal of antimicrobial chemotherapy 2012-12, Vol.67 (12), p.2814-2820 |
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| cites | cdi_FETCH-LOGICAL-c414t-9fe96099b0a1d4f473c3452a41bb79a0cdf1a63d5c408e91b596ba1bbf240a893 |
| container_end_page | 2820 |
| container_issue | 12 |
| container_start_page | 2814 |
| container_title | Journal of antimicrobial chemotherapy |
| container_volume | 67 |
| creator | REMY, Joan M TOW-KEOGH, Cheryl A MCCONNELL, Timothy S DALTON, James M DEVITO, Joseph A |
| description | To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR).
Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined.
Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to |
| doi_str_mv | 10.1093/jac/dks307 |
| format | article |
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Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined.
Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to <9.5 × 10(-11). Delafloxacin MPCs were one to four times the MIC for any isolate, lower than those of comparator quinolones. Some delafloxacin-selected mutants showed a fitness cost when co-cultured with the parent strain.
Delafloxacin demonstrates excellent antibacterial potency and exhibits a low probability for the selection of resistant mutants in MRSA. Although mutants can be selected at low frequencies in vitro from quinolone-resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can be observed. Consequently delafloxacin warrants further investigation for the potential treatment of drug-resistant MRSA infections.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dks307</identifier><identifier>PMID: 22875850</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Agar ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Bacterial diseases ; Biological and medical sciences ; Cell migration ; Cells ; Clinical isolates ; DNA Mutational Analysis ; DNA, Bacterial - genetics ; Drug resistance ; Drug Resistance, Bacterial ; Fitness ; Growth rate ; Human bacterial diseases ; Humans ; Infection ; Infectious diseases ; Medical sciences ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Methicillin-Resistant Staphylococcus aureus - growth & development ; Microbial Sensitivity Tests ; Minimum inhibitory concentration ; Mutation ; Pharmacology. Drug treatments ; Polymerase Chain Reaction ; Quinolones ; Quinolones - pharmacology ; Resistant mutant ; Selection, Genetic ; Staphylococcal infections, streptococcal infections, pneumococcal infections ; Staphylococcus aureus ; Staphylococcus infections</subject><ispartof>Journal of antimicrobial chemotherapy, 2012-12, Vol.67 (12), p.2814-2820</ispartof><rights>2014 INIST-CNRS</rights><rights>Copyright Oxford Publishing Limited(England) Dec 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-9fe96099b0a1d4f473c3452a41bb79a0cdf1a63d5c408e91b596ba1bbf240a893</citedby><cites>FETCH-LOGICAL-c414t-9fe96099b0a1d4f473c3452a41bb79a0cdf1a63d5c408e91b596ba1bbf240a893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26646601$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22875850$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>REMY, Joan M</creatorcontrib><creatorcontrib>TOW-KEOGH, Cheryl A</creatorcontrib><creatorcontrib>MCCONNELL, Timothy S</creatorcontrib><creatorcontrib>DALTON, James M</creatorcontrib><creatorcontrib>DEVITO, Joseph A</creatorcontrib><title>Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR).
Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined.
Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to <9.5 × 10(-11). Delafloxacin MPCs were one to four times the MIC for any isolate, lower than those of comparator quinolones. Some delafloxacin-selected mutants showed a fitness cost when co-cultured with the parent strain.
Delafloxacin demonstrates excellent antibacterial potency and exhibits a low probability for the selection of resistant mutants in MRSA. Although mutants can be selected at low frequencies in vitro from quinolone-resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can be observed. Consequently delafloxacin warrants further investigation for the potential treatment of drug-resistant MRSA infections.</description><subject>Agar</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Cell migration</subject><subject>Cells</subject><subject>Clinical isolates</subject><subject>DNA Mutational Analysis</subject><subject>DNA, Bacterial - genetics</subject><subject>Drug resistance</subject><subject>Drug Resistance, Bacterial</subject><subject>Fitness</subject><subject>Growth rate</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infection</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>Methicillin-Resistant Staphylococcus aureus - drug effects</subject><subject>Methicillin-Resistant Staphylococcus aureus - growth & development</subject><subject>Microbial Sensitivity Tests</subject><subject>Minimum inhibitory concentration</subject><subject>Mutation</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymerase Chain Reaction</subject><subject>Quinolones</subject><subject>Quinolones - pharmacology</subject><subject>Resistant mutant</subject><subject>Selection, Genetic</subject><subject>Staphylococcal infections, streptococcal infections, pneumococcal infections</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus infections</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqF0U2LFDEQBuAgijuuXvwB0iCCCO1WPruzt2XxCxY8qOemOp04GTOdMUmr468348wqePFUkHp4IfUS8pjCSwqaX2zQXExfMofuDllRoaBloOldsgIOsu2E5GfkQc4bAFBS9ffJGWN9J3sJK_L9yhT_zZd9E10z2YAuxB9o_NzgZ_RzLs3WlrU3PgQ_t8lmnwvOpflQcLfeh2iiMUtucEl2yZfNLTC2yTbYmh1r0jw1Zo0JTbHJ_8TD40Nyz2HI9tFpnpNPr199vH7b3rx_8-766qY1gorSame1Aq1HQDoJJzpuuJAMBR3HTiOYyVFUfJJGQG81HaVWI9alYwKw1_ycPD_m7lL8uthchq3PxoaAs41LHiirZ9CMKvZ_SiXtABj0lT79h27ikub6kd-Kd1Tog3pxVCbFnJN1wy75Lab9QGE4NDfU5oZjcxU_OUUu49ZOf-htVRU8OwHMBoNL9co-_3VKCaWA8l_u76Ou</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>REMY, Joan M</creator><creator>TOW-KEOGH, Cheryl A</creator><creator>MCCONNELL, Timothy S</creator><creator>DALTON, James M</creator><creator>DEVITO, Joseph A</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><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>20121201</creationdate><title>Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization</title><author>REMY, Joan M ; TOW-KEOGH, Cheryl A ; MCCONNELL, Timothy S ; DALTON, James M ; DEVITO, Joseph A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-9fe96099b0a1d4f473c3452a41bb79a0cdf1a63d5c408e91b596ba1bbf240a893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Agar</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Bacterial diseases</topic><topic>Biological and medical sciences</topic><topic>Cell migration</topic><topic>Cells</topic><topic>Clinical isolates</topic><topic>DNA Mutational Analysis</topic><topic>DNA, Bacterial - genetics</topic><topic>Drug resistance</topic><topic>Drug Resistance, Bacterial</topic><topic>Fitness</topic><topic>Growth rate</topic><topic>Human bacterial diseases</topic><topic>Humans</topic><topic>Infection</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>Methicillin-Resistant Staphylococcus aureus - drug effects</topic><topic>Methicillin-Resistant Staphylococcus aureus - growth & development</topic><topic>Microbial Sensitivity Tests</topic><topic>Minimum inhibitory concentration</topic><topic>Mutation</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymerase Chain Reaction</topic><topic>Quinolones</topic><topic>Quinolones - pharmacology</topic><topic>Resistant mutant</topic><topic>Selection, Genetic</topic><topic>Staphylococcal infections, streptococcal infections, pneumococcal infections</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus infections</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>REMY, Joan M</creatorcontrib><creatorcontrib>TOW-KEOGH, Cheryl A</creatorcontrib><creatorcontrib>MCCONNELL, Timothy S</creatorcontrib><creatorcontrib>DALTON, James M</creatorcontrib><creatorcontrib>DEVITO, Joseph A</creatorcontrib><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>REMY, Joan M</au><au>TOW-KEOGH, Cheryl A</au><au>MCCONNELL, Timothy S</au><au>DALTON, James M</au><au>DEVITO, Joseph A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>67</volume><issue>12</issue><spage>2814</spage><epage>2820</epage><pages>2814-2820</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><coden>JACHDX</coden><abstract>To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR).
Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined.
Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to <9.5 × 10(-11). Delafloxacin MPCs were one to four times the MIC for any isolate, lower than those of comparator quinolones. Some delafloxacin-selected mutants showed a fitness cost when co-cultured with the parent strain.
Delafloxacin demonstrates excellent antibacterial potency and exhibits a low probability for the selection of resistant mutants in MRSA. Although mutants can be selected at low frequencies in vitro from quinolone-resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can be observed. Consequently delafloxacin warrants further investigation for the potential treatment of drug-resistant MRSA infections.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22875850</pmid><doi>10.1093/jac/dks307</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antimicrobial chemotherapy, 2012-12, Vol.67 (12), p.2814-2820 |
| issn | 0305-7453 1460-2091 |
| language | eng |
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| source | Oxford Journals Online |
| subjects | Agar Anti-Bacterial Agents - pharmacology Antibiotics Antibiotics. Antiinfectious agents. Antiparasitic agents Bacterial diseases Biological and medical sciences Cell migration Cells Clinical isolates DNA Mutational Analysis DNA, Bacterial - genetics Drug resistance Drug Resistance, Bacterial Fitness Growth rate Human bacterial diseases Humans Infection Infectious diseases Medical sciences Methicillin-Resistant Staphylococcus aureus - drug effects Methicillin-Resistant Staphylococcus aureus - growth & development Microbial Sensitivity Tests Minimum inhibitory concentration Mutation Pharmacology. Drug treatments Polymerase Chain Reaction Quinolones Quinolones - pharmacology Resistant mutant Selection, Genetic Staphylococcal infections, streptococcal infections, pneumococcal infections Staphylococcus aureus Staphylococcus infections |
| title | Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization |
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