Dariusz A Hareza, Yehudit Bergman, Emily Jacobs, Jennifer Lu, Nancy D Hanson, Rick Conzemius, Sara E Cosgrove, Anthony D Harris, Patricia J Simner, Pranita D Tamma
{"title":"美国中大西洋地区头孢曲松耐药肠杆菌血流感染中β-内酰胺酶的分子流行病学研究","authors":"Dariusz A Hareza, Yehudit Bergman, Emily Jacobs, Jennifer Lu, Nancy D Hanson, Rick Conzemius, Sara E Cosgrove, Anthony D Harris, Patricia J Simner, Pranita D Tamma","doi":"10.1128/aac.01258-24","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>ampC</i> genes both in bacterial chromosomes (c-<i>ampC</i>) and on plasmids (p-<i>ampC</i>). Mutations in promoter or attenuator regions of the <i>Escherichia coli</i> c-<i>ampC</i> gene (i.e., <i>bla</i><sub>EC</sub> gene) with the potential to result in <i>ampC</i> derepression were investigated. The presence of ESBL or <i>ampC</i> genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and <i>ampC</i> genes. ESBL families were identified among 398 (80%) patients: <i>bla</i><sub>CTX-M</sub> (<i>n</i> = 370), <i>bla</i><sub>SHV</sub> (<i>n</i> = 17), <i>bla</i><sub>OXY</sub> (<i>n</i> = 14), and <i>bla</i><sub>VEB</sub> (<i>n</i> = 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following: <i>E. coli</i> (67%), <i>Klebsiella pneumoniae</i> (24%), <i>Klebsiella oxytoca</i> (4%), <i>Proteus mirabilis</i> (2%), <i>Enterobacter cloacae</i> complex (2%), <i>Klebsiella aerogenes</i> (1%), <i>Providencia stuartii</i> (<1%), and <i>Serratia marcescens</i> (<1%). c-<i>ampC</i> genes were identified in 374 (75%) of the 500 isolates. Only 7% of <i>E. coli</i> isolates with mutations in the promoter or attenuator region of the c-<i>ampC</i> gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-<i>ampC</i> genes were confirmed in 25 (5%) of the 500 isolates: <i>bla</i><sub>CMY-59</sub> (72%) and <i>bla</i><sub>DHA-1</sub> (28%; confined to <i>E. coli</i> [92%] and <i>K. pneumoniae</i> [8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and <i>ampC</i> genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the <i>E. coli</i> c-<i>ampC</i> gene do not appear to contribute significantly to increased AmpC production in this species.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0125824"},"PeriodicalIF":4.1000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881560/pdf/","citationCount":"0","resultStr":"{\"title\":\"Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States.\",\"authors\":\"Dariusz A Hareza, Yehudit Bergman, Emily Jacobs, Jennifer Lu, Nancy D Hanson, Rick Conzemius, Sara E Cosgrove, Anthony D Harris, Patricia J Simner, Pranita D Tamma\",\"doi\":\"10.1128/aac.01258-24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>ampC</i> genes both in bacterial chromosomes (c-<i>ampC</i>) and on plasmids (p-<i>ampC</i>). Mutations in promoter or attenuator regions of the <i>Escherichia coli</i> c-<i>ampC</i> gene (i.e., <i>bla</i><sub>EC</sub> gene) with the potential to result in <i>ampC</i> derepression were investigated. The presence of ESBL or <i>ampC</i> genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and <i>ampC</i> genes. ESBL families were identified among 398 (80%) patients: <i>bla</i><sub>CTX-M</sub> (<i>n</i> = 370), <i>bla</i><sub>SHV</sub> (<i>n</i> = 17), <i>bla</i><sub>OXY</sub> (<i>n</i> = 14), and <i>bla</i><sub>VEB</sub> (<i>n</i> = 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following: <i>E. coli</i> (67%), <i>Klebsiella pneumoniae</i> (24%), <i>Klebsiella oxytoca</i> (4%), <i>Proteus mirabilis</i> (2%), <i>Enterobacter cloacae</i> complex (2%), <i>Klebsiella aerogenes</i> (1%), <i>Providencia stuartii</i> (<1%), and <i>Serratia marcescens</i> (<1%). c-<i>ampC</i> genes were identified in 374 (75%) of the 500 isolates. Only 7% of <i>E. coli</i> isolates with mutations in the promoter or attenuator region of the c-<i>ampC</i> gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-<i>ampC</i> genes were confirmed in 25 (5%) of the 500 isolates: <i>bla</i><sub>CMY-59</sub> (72%) and <i>bla</i><sub>DHA-1</sub> (28%; confined to <i>E. coli</i> [92%] and <i>K. pneumoniae</i> [8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and <i>ampC</i> genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the <i>E. coli</i> c-<i>ampC</i> gene do not appear to contribute significantly to increased AmpC production in this species.</p>\",\"PeriodicalId\":8152,\"journal\":{\"name\":\"Antimicrobial Agents and Chemotherapy\",\"volume\":\" \",\"pages\":\"e0125824\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-03-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881560/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Antimicrobial Agents and Chemotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1128/aac.01258-24\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antimicrobial Agents and Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/aac.01258-24","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
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 Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities. Whole-genome sequencing identified extended-spectrum β-lactamase (ESBL) and ampC genes both in bacterial chromosomes (c-ampC) and on plasmids (p-ampC). Mutations in promoter or attenuator regions of the Escherichia coli c-ampC gene (i.e., blaEC gene) with the potential to result in ampC derepression were investigated. The presence of ESBL or ampC genes was confirmed in 497 (99.4%) isolates. Two hundred seventy-nine (55.8%) isolates had both ESBL and ampC genes. ESBL families were identified among 398 (80%) patients: blaCTX-M (n = 370), blaSHV (n = 17), blaOXY (n = 14), and blaVEB (n = 5). Ceftriaxone-resistant Enterobacterales species carrying ESBL genes included the following: E. coli (67%), Klebsiella pneumoniae (24%), Klebsiella oxytoca (4%), Proteus mirabilis (2%), Enterobacter cloacae complex (2%), Klebsiella aerogenes (1%), Providencia stuartii (<1%), and Serratia marcescens (<1%). c-ampC genes were identified in 374 (75%) of the 500 isolates. Only 7% of E. coli isolates with mutations in the promoter or attenuator region of the c-ampC gene exhibited resistance to cefoxitin, a proxy for increased AmpC production. Two p-ampC genes were confirmed in 25 (5%) of the 500 isolates: blaCMY-59 (72%) and blaDHA-1 (28%; confined to E. coli [92%] and K. pneumoniae [8%]). Until comprehensive β-lactamase molecular testing is available, the species-specific prevalence of ESBL and ampC genes in ceftriaxone-resistant Enterobacterales should be considered to promote effective albeit judicious antibiotic prescribing. Mutations in promoter or attenuator regions of the E. coli c-ampC gene do not appear to contribute significantly to increased AmpC production in this species.
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Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
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