Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients
To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance. The susceptib...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2014-10, Vol.69 (10), p.2690-2698 |
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| creator | Sherrard, Laura J Schaible, Bettina Graham, Kathryn A McGrath, Stef J McIlreavey, Leanne Hatch, Joseph Wolfgang, Matthew C Muhlebach, Marianne S Gilpin, Deirdre F Schneiders, Thamarai Elborn, J Stuart Tunney, Michael M |
| description | To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance.
The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps.
Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P |
| doi_str_mv | 10.1093/jac/dku192 |
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The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps.
Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps.
This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dku192</identifier><identifier>PMID: 24917582</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Amino Acid Substitution ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Bacteroidaceae Infections - microbiology ; beta-Lactamases - genetics ; Case-Control Studies ; Ceftazidime - pharmacology ; Cephalosporin Resistance - genetics ; Cystic fibrosis ; Cystic Fibrosis - microbiology ; Drug resistance ; Drug Resistance, Microbial - genetics ; Enzymes ; Genes ; Genes, Bacterial ; Genotype ; Genotype & phenotype ; Humans ; Microbial Sensitivity Tests ; Mutation ; Original Research ; Prevotella - drug effects ; Prevotella - genetics ; Prevotella - isolation & purification ; Tetracycline - pharmacology ; Tetracycline Resistance - genetics ; United Kingdom</subject><ispartof>Journal of antimicrobial chemotherapy, 2014-10, Vol.69 (10), p.2690-2698</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford Publishing Limited(England) Oct 2014</rights><rights>The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-c183abe447737942b56d295a09b62117a931d9b9e7f2752974e8bcc3701ad7cd3</citedby><cites>FETCH-LOGICAL-c472t-c183abe447737942b56d295a09b62117a931d9b9e7f2752974e8bcc3701ad7cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24917582$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sherrard, Laura J</creatorcontrib><creatorcontrib>Schaible, Bettina</creatorcontrib><creatorcontrib>Graham, Kathryn A</creatorcontrib><creatorcontrib>McGrath, Stef J</creatorcontrib><creatorcontrib>McIlreavey, Leanne</creatorcontrib><creatorcontrib>Hatch, Joseph</creatorcontrib><creatorcontrib>Wolfgang, Matthew C</creatorcontrib><creatorcontrib>Muhlebach, Marianne S</creatorcontrib><creatorcontrib>Gilpin, Deirdre F</creatorcontrib><creatorcontrib>Schneiders, Thamarai</creatorcontrib><creatorcontrib>Elborn, J Stuart</creatorcontrib><creatorcontrib>Tunney, Michael M</creatorcontrib><title>Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>To investigate mechanisms of reduced susceptibility to commonly used antibiotics in Prevotella cultured from patients with cystic fibrosis (CF), patients with invasive infection and healthy control subjects and to determine whether genotype can be used to predict phenotypic resistance.
The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps.
Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps.
This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.</description><subject>Amino Acid Substitution</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Bacteroidaceae Infections - microbiology</subject><subject>beta-Lactamases - genetics</subject><subject>Case-Control Studies</subject><subject>Ceftazidime - pharmacology</subject><subject>Cephalosporin Resistance - genetics</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - microbiology</subject><subject>Drug resistance</subject><subject>Drug Resistance, Microbial - genetics</subject><subject>Enzymes</subject><subject>Genes</subject><subject>Genes, Bacterial</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Microbial Sensitivity Tests</subject><subject>Mutation</subject><subject>Original Research</subject><subject>Prevotella - drug effects</subject><subject>Prevotella - genetics</subject><subject>Prevotella - isolation & purification</subject><subject>Tetracycline - pharmacology</subject><subject>Tetracycline Resistance - genetics</subject><subject>United Kingdom</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc2KFDEUhYMoTju68QEk4EaFcvJb6WwGpLFVGNGFrkMquTWTtjopk9RAP4sva9oeB13dxf3OOfdyEHpOyVtKNL_YWXfhfyxUswdoRUVPOkY0fYhWhBPZKSH5GXpSyo4Q0st-_RidMaGpkmu2Qr8-g7uxMZR9wWnEGfziwOOyFAdzDUOYQj1gGz2-hpjqYQ4Oz40KroYUjxIbj1iqbZGhhFJtdIBDxF8z3KYK02RxKGmytfmOOe2xO5QjPYYhpybArzbb138iYordZotnWwPEWp6iR6OdCjy7m-fo-_b9t83H7urLh0-bd1edE4rVztE1twMIoRRXWrBB9p5paYkeekapsppTrwcNamRKMq0ErAfnuCLUeuU8P0eXJ995GfbgXcvOdjJzDnubDybZYP7fxHBjrtOtEbQXVJBm8PLOIKefC5RqdmnJsd1sqGyIJD1XjXpzolx7u2QY7xMoMcciTSvSnIps8It_b7pH_zbHfwNC_535</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Sherrard, Laura J</creator><creator>Schaible, Bettina</creator><creator>Graham, Kathryn A</creator><creator>McGrath, Stef J</creator><creator>McIlreavey, Leanne</creator><creator>Hatch, Joseph</creator><creator>Wolfgang, Matthew C</creator><creator>Muhlebach, Marianne S</creator><creator>Gilpin, Deirdre F</creator><creator>Schneiders, Thamarai</creator><creator>Elborn, J Stuart</creator><creator>Tunney, Michael M</creator><general>Oxford Publishing Limited (England)</general><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>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>5PM</scope></search><sort><creationdate>20141001</creationdate><title>Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients</title><author>Sherrard, Laura J ; 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The susceptibility of 157 Prevotella isolates to seven antibiotics was compared, with detection of resistance genes (cfxA-type gene, ermF and tetQ), mutations within the CfxA-type β-lactamase and expression of efflux pumps.
Prevotella isolates positive for a cfxA-type gene had higher MICs of amoxicillin and ceftazidime compared with isolates negative for this gene (P < 0.001). A mutation within the CfxA-type β-lactamase (Y239D) was associated with ceftazidime resistance (P = 0.011). The UK CF isolates were 5.3-fold, 2.7-fold and 5.7-fold more likely to harbour ermF compared with the US CF, UK invasive and UK healthy control isolates, respectively. Higher concentrations of azithromycin (P < 0.001) and clindamycin (P < 0.001) were also required to inhibit the growth of the ermF-positive isolates compared with ermF-negative isolates. Furthermore, tetQ-positive Prevotella isolates had higher MICs of tetracycline (P = 0.001) and doxycycline (P < 0.001) compared with tetQ-negative isolates. Prevotella spp. were also shown, for the first time, to express resistance nodulation division (RND)-type efflux pumps.
This study has demonstrated that Prevotella isolated from various sources harbour a common pool of resistance genes and possess RND-type efflux pumps, which may contribute to tetracycline resistance. The findings indicate that antibiotic resistance is common in Prevotella spp., but the genotypic traits investigated do not reflect phenotypic antibiotic resistance in every instance.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>24917582</pmid><doi>10.1093/jac/dku192</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amino Acid Substitution Anti-Bacterial Agents - pharmacology Antibiotics Bacteroidaceae Infections - microbiology beta-Lactamases - genetics Case-Control Studies Ceftazidime - pharmacology Cephalosporin Resistance - genetics Cystic fibrosis Cystic Fibrosis - microbiology Drug resistance Drug Resistance, Microbial - genetics Enzymes Genes Genes, Bacterial Genotype Genotype & phenotype Humans Microbial Sensitivity Tests Mutation Original Research Prevotella - drug effects Prevotella - genetics Prevotella - isolation & purification Tetracycline - pharmacology Tetracycline Resistance - genetics United Kingdom |
| title | Mechanisms of reduced susceptibility and genotypic prediction of antibiotic resistance in Prevotella isolated from cystic fibrosis (CF) and non-CF patients |
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