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. 2025 Mar 5;69(3):e0125824.
doi: 10.1128/aac.01258-24. Epub 2025 Jan 27.

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

Dariusz A Hareza  1 , Yehudit Bergman  2   3 , Emily Jacobs  2 , Jennifer Lu  2 , Nancy D Hanson  4 , Rick Conzemius  5 , Sara E Cosgrove  1 , Anthony D Harris  6 , Patricia J Simner #  1   2 , Pranita D Tamma #  3
Affiliations

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

Dariusz A Hareza et al. Antimicrob Agents Chemother. .

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.

Keywords: CMY; CTX-M; DHA; EC; ESBLs; SHV; ampC.

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Conflict of interest statement

P.J.S. reports receiving grants and personal fees from Accelerate Diagnostics, OpGen, and BD Diagnostics; grants from bioMerieux, Inc., Affinity Biosensors, and Hardy Diagnostics; and personal fees from Roche Diagnostics, Shionogi, Inc., and GeneCapture outside the submitted work. R.C. is an employee of Ares Genetics. S.E.C. reports receiving personal fees from the Duke Clinical Research Institute and Debiopharm, outside of the submitted work. All other authors report no disclosures.

Figures

Fig 1
Fig 1
A deeper investigation into c-ampC genes in E. coli.
See this image and copyright information in PMC

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