Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Antimicrobial Agents and Chemotherapy Pub Date : 2025-03-05 Epub Date: 2025-01-27 DOI:10.1128/aac.01258-24
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
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引用次数: 0

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 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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来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: 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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