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In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes
We describe the emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing r...
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| Published in: | Antimicrobial agents and chemotherapy 2024-12, Vol.68 (12), p.e0130724 |
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| Main Authors: | , , , , , , , , , , , , |
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| container_issue | 12 |
| container_start_page | e0130724 |
| container_title | Antimicrobial agents and chemotherapy |
| container_volume | 68 |
| creator | Rodríguez-Pallares, Salud Blanco-Martín, Tania Lence, Emilio Aja-Macaya, Pablo Sánchez-Peña, Lucía González-Pinto, Lucía Rodríguez-Mayo, María Fernández-González, Ana Galán-Sánchez, Fátima Beceiro, Alejandro González-Bello, Concepción Bou, Germán Arca-Suárez, Jorge |
| description | We describe the
emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical
isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype. |
| doi_str_mv | 10.1128/aac.01307-24 |
| format | article |
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emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical
isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype.</description><identifier>ISSN: 0066-4804</identifier><identifier>ISSN: 1098-6596</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/aac.01307-24</identifier><identifier>PMID: 39503481</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Anti-Bacterial Agents - pharmacology ; Antimicrobial Chemotherapy ; Azabicyclo Compounds - pharmacology ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; beta-Lactamases - genetics ; beta-Lactamases - metabolism ; Ceftazidime - pharmacology ; Drug Combinations ; Drug Resistance, Multiple, Bacterial - genetics ; Enterobacter aerogenes - drug effects ; Enterobacter aerogenes - enzymology ; Enterobacter aerogenes - genetics ; Humans ; Klebsiella Infections - drug therapy ; Klebsiella Infections - microbiology ; Mechanisms of Resistance ; Microbial Sensitivity Tests ; Mutation ; Whole Genome Sequencing</subject><ispartof>Antimicrobial agents and chemotherapy, 2024-12, Vol.68 (12), p.e0130724</ispartof><rights>Copyright © 2024 American Society for Microbiology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a212t-fe8c2c710bdb5d6d7b5f0014367cd5bb5a318b18c163909eaf6625962af8978c3</cites><orcidid>0000-0002-4248-503X ; 0000-0003-0101-6701 ; 0000-0001-8837-0062 ; 0000-0002-8270-0259 ; 0000-0002-6340-7815</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.asm.org/doi/pdf/10.1128/aac.01307-24$$EPDF$$P50$$Gasm2$$H</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/aac.01307-24$$EHTML$$P50$$Gasm2$$H</linktohtml><link.rule.ids>314,780,784,3188,27924,27925,52751,52752,52753</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39503481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Poirel, Laurent</contributor><creatorcontrib>Rodríguez-Pallares, Salud</creatorcontrib><creatorcontrib>Blanco-Martín, Tania</creatorcontrib><creatorcontrib>Lence, Emilio</creatorcontrib><creatorcontrib>Aja-Macaya, Pablo</creatorcontrib><creatorcontrib>Sánchez-Peña, Lucía</creatorcontrib><creatorcontrib>González-Pinto, Lucía</creatorcontrib><creatorcontrib>Rodríguez-Mayo, María</creatorcontrib><creatorcontrib>Fernández-González, Ana</creatorcontrib><creatorcontrib>Galán-Sánchez, Fátima</creatorcontrib><creatorcontrib>Beceiro, Alejandro</creatorcontrib><creatorcontrib>González-Bello, Concepción</creatorcontrib><creatorcontrib>Bou, Germán</creatorcontrib><creatorcontrib>Arca-Suárez, Jorge</creatorcontrib><title>In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>We describe the
emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical
isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antimicrobial Chemotherapy</subject><subject>Azabicyclo Compounds - pharmacology</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>beta-Lactamases - genetics</subject><subject>beta-Lactamases - metabolism</subject><subject>Ceftazidime - pharmacology</subject><subject>Drug Combinations</subject><subject>Drug Resistance, Multiple, Bacterial - genetics</subject><subject>Enterobacter aerogenes - drug effects</subject><subject>Enterobacter aerogenes - enzymology</subject><subject>Enterobacter aerogenes - genetics</subject><subject>Humans</subject><subject>Klebsiella Infections - drug therapy</subject><subject>Klebsiella Infections - microbiology</subject><subject>Mechanisms of Resistance</subject><subject>Microbial Sensitivity Tests</subject><subject>Mutation</subject><subject>Whole Genome Sequencing</subject><issn>0066-4804</issn><issn>1098-6596</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp1kc9uFDEMxiMEokvhxhnlCBLT5t9kMsdqBaWiEhc4R07GaVNNJksysxI8AA_Eg_BMne0WbpwsWz_bnz8T8pqzM86FOQfwZ4xL1jVCPSEbznrT6LbXT8mGMa0bZZg6IS9qvWNr3vbsOTmRfcukMnxDfl1NdB_3mWLCcoOTR5oDLVhjneGQzZl6DDP8jENMeA776MDPkOh8W_Jyc0tTHmKIHuaYp0OvX-sp15xgpBdpt6V_fjfjQwtUpHGin0d0NeI4AgUseV2K9SV5FmCs-OoxnpJvHz983X5qrr9cXm0vrhsQXMxNQOOF7zhzg2sHPXSuDYxxJXXnh9a5FiQ3jhvPtexZjxC0FqsXAoLpO-PlKXl7nLsr-fuCdbYpVn_QMmFeqpVcKN0LpfiKvj-ivuRaCwa7KzFB-WE5swfn7eq8fXDeCrXi74441CTsXV7KtB7yP_bNo4rFJRz-Df77FnkP3VOOmA</recordid><startdate>20241205</startdate><enddate>20241205</enddate><creator>Rodríguez-Pallares, Salud</creator><creator>Blanco-Martín, Tania</creator><creator>Lence, Emilio</creator><creator>Aja-Macaya, Pablo</creator><creator>Sánchez-Peña, Lucía</creator><creator>González-Pinto, Lucía</creator><creator>Rodríguez-Mayo, María</creator><creator>Fernández-González, Ana</creator><creator>Galán-Sánchez, Fátima</creator><creator>Beceiro, Alejandro</creator><creator>González-Bello, Concepción</creator><creator>Bou, Germán</creator><creator>Arca-Suárez, Jorge</creator><general>American Society for Microbiology</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><orcidid>https://orcid.org/0000-0002-4248-503X</orcidid><orcidid>https://orcid.org/0000-0003-0101-6701</orcidid><orcidid>https://orcid.org/0000-0001-8837-0062</orcidid><orcidid>https://orcid.org/0000-0002-8270-0259</orcidid><orcidid>https://orcid.org/0000-0002-6340-7815</orcidid></search><sort><creationdate>20241205</creationdate><title>In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes</title><author>Rodríguez-Pallares, Salud ; Blanco-Martín, Tania ; Lence, Emilio ; Aja-Macaya, Pablo ; Sánchez-Peña, Lucía ; González-Pinto, Lucía ; Rodríguez-Mayo, María ; Fernández-González, Ana ; Galán-Sánchez, Fátima ; Beceiro, Alejandro ; González-Bello, Concepción ; Bou, Germán ; Arca-Suárez, Jorge</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a212t-fe8c2c710bdb5d6d7b5f0014367cd5bb5a318b18c163909eaf6625962af8978c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antimicrobial Chemotherapy</topic><topic>Azabicyclo Compounds - pharmacology</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>beta-Lactamases - genetics</topic><topic>beta-Lactamases - metabolism</topic><topic>Ceftazidime - pharmacology</topic><topic>Drug Combinations</topic><topic>Drug Resistance, Multiple, Bacterial - genetics</topic><topic>Enterobacter aerogenes - drug effects</topic><topic>Enterobacter aerogenes - enzymology</topic><topic>Enterobacter aerogenes - genetics</topic><topic>Humans</topic><topic>Klebsiella Infections - drug therapy</topic><topic>Klebsiella Infections - microbiology</topic><topic>Mechanisms of Resistance</topic><topic>Microbial Sensitivity Tests</topic><topic>Mutation</topic><topic>Whole Genome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodríguez-Pallares, Salud</creatorcontrib><creatorcontrib>Blanco-Martín, Tania</creatorcontrib><creatorcontrib>Lence, Emilio</creatorcontrib><creatorcontrib>Aja-Macaya, Pablo</creatorcontrib><creatorcontrib>Sánchez-Peña, Lucía</creatorcontrib><creatorcontrib>González-Pinto, Lucía</creatorcontrib><creatorcontrib>Rodríguez-Mayo, María</creatorcontrib><creatorcontrib>Fernández-González, Ana</creatorcontrib><creatorcontrib>Galán-Sánchez, Fátima</creatorcontrib><creatorcontrib>Beceiro, Alejandro</creatorcontrib><creatorcontrib>González-Bello, Concepción</creatorcontrib><creatorcontrib>Bou, Germán</creatorcontrib><creatorcontrib>Arca-Suárez, Jorge</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>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodríguez-Pallares, Salud</au><au>Blanco-Martín, Tania</au><au>Lence, Emilio</au><au>Aja-Macaya, Pablo</au><au>Sánchez-Peña, Lucía</au><au>González-Pinto, Lucía</au><au>Rodríguez-Mayo, María</au><au>Fernández-González, Ana</au><au>Galán-Sánchez, Fátima</au><au>Beceiro, Alejandro</au><au>González-Bello, Concepción</au><au>Bou, Germán</au><au>Arca-Suárez, Jorge</au><au>Poirel, Laurent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2024-12-05</date><risdate>2024</risdate><volume>68</volume><issue>12</issue><spage>e0130724</spage><pages>e0130724-</pages><issn>0066-4804</issn><issn>1098-6596</issn><eissn>1098-6596</eissn><abstract>We describe the
emergence of resistance to ceftazidime/avibactam via modification of AmpC in a clinical
isolate during therapy with this combination. Paired ceftazidime/avibactam-susceptible/resistant isolates were obtained before and during ceftazidime/avibactam treatment. Whole genome sequencing revealed a differential mutation in AmpC (R148W) in the ceftazidime/avibactam-resistant isolate. Molecular cloning and structural studies confirmed the impact of this substitution, which affects the architecture of the H10 helix, on the evolved resistant phenotype.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>39503481</pmid><doi>10.1128/aac.01307-24</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4248-503X</orcidid><orcidid>https://orcid.org/0000-0003-0101-6701</orcidid><orcidid>https://orcid.org/0000-0001-8837-0062</orcidid><orcidid>https://orcid.org/0000-0002-8270-0259</orcidid><orcidid>https://orcid.org/0000-0002-6340-7815</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0066-4804 |
| ispartof | Antimicrobial agents and chemotherapy, 2024-12, Vol.68 (12), p.e0130724 |
| issn | 0066-4804 1098-6596 1098-6596 |
| language | eng |
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| source | American Society for Microbiology Journals |
| subjects | Anti-Bacterial Agents - pharmacology Antimicrobial Chemotherapy Azabicyclo Compounds - pharmacology Bacterial Proteins - genetics Bacterial Proteins - metabolism beta-Lactamases - genetics beta-Lactamases - metabolism Ceftazidime - pharmacology Drug Combinations Drug Resistance, Multiple, Bacterial - genetics Enterobacter aerogenes - drug effects Enterobacter aerogenes - enzymology Enterobacter aerogenes - genetics Humans Klebsiella Infections - drug therapy Klebsiella Infections - microbiology Mechanisms of Resistance Microbial Sensitivity Tests Mutation Whole Genome Sequencing |
| title | In vivo emergence of resistance to ceftazidime/avibactam through modification of chromosomal AmpC β-lactamase in Klebsiella aerogenes |
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