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Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States
Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Marylan...
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description | Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities. Whole-genome sequencing identified extended-spectrum β-lactamase (ESBL) and
genes both in bacterial chromosomes (c-
) and on plasmids (p-
). Mutations in promoter or attenuator regions of the
c-
gene (i.e.,
gene) with the potential to result in
derepression were investigated. The presence of ESBL or
genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and
genes. ESBL families were identified among 398 (80%) patients:
(
= 370),
(
= 17),
(
= 14), and
(
= 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following:
(67%),
(24%),
(4%),
(2%),
complex (2%),
(1%),
( |
doi_str_mv | 10.1128/aac.01258-24 |
format | article |
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genes both in bacterial chromosomes (c-
) and on plasmids (p-
). Mutations in promoter or attenuator regions of the
c-
gene (i.e.,
gene) with the potential to result in
derepression were investigated. The presence of ESBL or
genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and
genes. ESBL families were identified among 398 (80%) patients:
(
= 370),
(
= 17),
(
= 14), and
(
= 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following:
(67%),
(24%),
(4%),
(2%),
complex (2%),
(1%),
(<1%), and
(<1%). c-
genes were identified in 374 (75%) of the 500 isolates. Only 7% of
isolates with mutations in the promoter or attenuator region of the c-
gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-
genes were confirmed in 25 (5%) of the 500 isolates:
(72%) and
(28%; confined to
[92%] and
[8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and
genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the
c-
gene do not appear to contribute significantly to increased AmpC production in this species.</description><identifier>ISSN: 0066-4804</identifier><identifier>ISSN: 1098-6596</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/aac.01258-24</identifier><identifier>PMID: 39868794</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Clinical Microbiology ; Editor’s Pick ; Epidemiology and Surveillance</subject><ispartof>Antimicrobial agents and chemotherapy, 2025-01, p.e0125824</ispartof><rights>Copyright © 2025 Hareza et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a1654-830ae84407ca04befdfef18af4437848ee3abc730a430a9b9bc9cfeb75eb46e43</cites><orcidid>0000-0001-6134-151X ; 0000-0002-4143-6324</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.01258-24$$EPDF$$P50$$Gasm2$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/aac.01258-24$$EHTML$$P50$$Gasm2$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3175,27901,27902,52726,52727,52728</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39868794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Doernberg, Sarah</contributor><creatorcontrib>Hareza, Dariusz A</creatorcontrib><creatorcontrib>Bergman, Yehudit</creatorcontrib><creatorcontrib>Jacobs, Emily</creatorcontrib><creatorcontrib>Lu, Jennifer</creatorcontrib><creatorcontrib>Hanson, Nancy D</creatorcontrib><creatorcontrib>Conzemius, Rick</creatorcontrib><creatorcontrib>Cosgrove, Sara E</creatorcontrib><creatorcontrib>Harris, Anthony D</creatorcontrib><creatorcontrib>Simner, Patricia J</creatorcontrib><creatorcontrib>Tamma, Pranita D</creatorcontrib><title>Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities. Whole-genome sequencing identified extended-spectrum β-lactamase (ESBL) and
genes both in bacterial chromosomes (c-
) and on plasmids (p-
). Mutations in promoter or attenuator regions of the
c-
gene (i.e.,
gene) with the potential to result in
derepression were investigated. The presence of ESBL or
genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and
genes. ESBL families were identified among 398 (80%) patients:
(
= 370),
(
= 17),
(
= 14), and
(
= 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following:
(67%),
(24%),
(4%),
(2%),
complex (2%),
(1%),
(<1%), and
(<1%). c-
genes were identified in 374 (75%) of the 500 isolates. Only 7% of
isolates with mutations in the promoter or attenuator region of the c-
gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-
genes were confirmed in 25 (5%) of the 500 isolates:
(72%) and
(28%; confined to
[92%] and
[8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and
genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the
c-
gene do not appear to contribute significantly to increased AmpC production in this species.</description><subject>Clinical Microbiology</subject><subject>Editor’s Pick</subject><subject>Epidemiology and Surveillance</subject><issn>0066-4804</issn><issn>1098-6596</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNp1kUFPFjEQhhujkQ_0xpn0qAnFdre72z0SgkCC8aCcm2l3iiXd7UfbTeQv-HP8If4mCx9y8zCZTPLMm3feIeRQ8BMhGvUJwJ5w0XSKNfIV2Qg-KtZ3Y_-abDjveyYVl3tkP-c7Xudu5G_JXjuqXg2j3JBfX2JAuwZIFLd-wtnHEG8faHT0z28WwBaYIWOmfqEWXUkefsYFWcLsc4Gl0POlYIqmkpggVNKEGKdcEsJctxza4uPyJFB-IJ39xE5LqJve0pvFF5zotwIF8zvyxkHI-P65H5Cbz-ffzy7Z9deLq7PTawai7yRTLQdUUvLBApcG3eTQCQVOynZQUiG2YOxQKVlrNKOxo3Vohg6N7FG2B-TDTneb4v2KuejZZ4uhesK4Zt2KnvOhUbKt6PEOtSnmnNDpbfIzpActuH5MX9f09VP6unlU_rjDIc-NvotrWuoh_2OPnl2sZsbpRfjfa9q_iEKR-A</recordid><startdate>20250127</startdate><enddate>20250127</enddate><creator>Hareza, Dariusz A</creator><creator>Bergman, Yehudit</creator><creator>Jacobs, Emily</creator><creator>Lu, Jennifer</creator><creator>Hanson, Nancy D</creator><creator>Conzemius, Rick</creator><creator>Cosgrove, Sara E</creator><creator>Harris, Anthony D</creator><creator>Simner, Patricia J</creator><creator>Tamma, Pranita D</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6134-151X</orcidid><orcidid>https://orcid.org/0000-0002-4143-6324</orcidid></search><sort><creationdate>20250127</creationdate><title>Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States</title><author>Hareza, Dariusz A ; Bergman, Yehudit ; Jacobs, Emily ; Lu, Jennifer ; Hanson, Nancy D ; Conzemius, Rick ; Cosgrove, Sara E ; Harris, Anthony D ; Simner, Patricia J ; Tamma, Pranita D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a1654-830ae84407ca04befdfef18af4437848ee3abc730a430a9b9bc9cfeb75eb46e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Clinical Microbiology</topic><topic>Editor’s Pick</topic><topic>Epidemiology and Surveillance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hareza, Dariusz A</creatorcontrib><creatorcontrib>Bergman, Yehudit</creatorcontrib><creatorcontrib>Jacobs, Emily</creatorcontrib><creatorcontrib>Lu, Jennifer</creatorcontrib><creatorcontrib>Hanson, Nancy D</creatorcontrib><creatorcontrib>Conzemius, Rick</creatorcontrib><creatorcontrib>Cosgrove, Sara E</creatorcontrib><creatorcontrib>Harris, Anthony D</creatorcontrib><creatorcontrib>Simner, Patricia J</creatorcontrib><creatorcontrib>Tamma, Pranita D</creatorcontrib><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>Hareza, Dariusz A</au><au>Bergman, Yehudit</au><au>Jacobs, Emily</au><au>Lu, Jennifer</au><au>Hanson, Nancy D</au><au>Conzemius, Rick</au><au>Cosgrove, Sara E</au><au>Harris, Anthony D</au><au>Simner, Patricia J</au><au>Tamma, Pranita D</au><au>Doernberg, Sarah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2025-01-27</date><risdate>2025</risdate><spage>e0125824</spage><pages>e0125824-</pages><issn>0066-4804</issn><issn>1098-6596</issn><eissn>1098-6596</eissn><abstract>Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities. Whole-genome sequencing identified extended-spectrum β-lactamase (ESBL) and
genes both in bacterial chromosomes (c-
) and on plasmids (p-
). Mutations in promoter or attenuator regions of the
c-
gene (i.e.,
gene) with the potential to result in
derepression were investigated. The presence of ESBL or
genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and
genes. ESBL families were identified among 398 (80%) patients:
(
= 370),
(
= 17),
(
= 14), and
(
= 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following:
(67%),
(24%),
(4%),
(2%),
complex (2%),
(1%),
(<1%), and
(<1%). c-
genes were identified in 374 (75%) of the 500 isolates. Only 7% of
isolates with mutations in the promoter or attenuator region of the c-
gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-
genes were confirmed in 25 (5%) of the 500 isolates:
(72%) and
(28%; confined to
[92%] and
[8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and
genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the
c-
gene do not appear to contribute significantly to increased AmpC production in this species.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>39868794</pmid><doi>10.1128/aac.01258-24</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6134-151X</orcidid><orcidid>https://orcid.org/0000-0002-4143-6324</orcidid><oa>free_for_read</oa></addata></record> |
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source | American Society for Microbiology |
subjects | Clinical Microbiology Editor’s Pick Epidemiology and Surveillance |
title | Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States |
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