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. 2023 Jan 27;10(2):ofad038.
doi: 10.1093/ofid/ofad038. eCollection 2023 Feb.

Trends of β-Lactamase Occurrence Among Escherichia coli and Klebsiella pneumoniae in United States Hospitals During a 5-Year Period and Activity of Antimicrobial Agents Against Isolates Stratified by β-Lactamase Type

Mariana Castanheira  1 , John H Kimbrough  1 , Sean DeVries  1 , Rodrigo E Mendes  1 , Helio S Sader  1
Affiliations

Trends of β-Lactamase Occurrence Among Escherichia coli and Klebsiella pneumoniae in United States Hospitals During a 5-Year Period and Activity of Antimicrobial Agents Against Isolates Stratified by β-Lactamase Type

Mariana Castanheira et al. Open Forum Infect Dis. .

Abstract

Background: The temporal and longitudinal trends of β-lactamases and their associated susceptibility patterns were analyzed for Escherichia coli and Klebsiella pneumoniae isolates consecutively collected in 56 United States hospitals during 2016-2020.

Methods: Isolates (n = 19 453) were susceptibility tested by reference broth microdilution methods. Isolates that displayed minimum inhibitory concentration (MIC) values ≥2 mg/L for at least 2 of the following compounds-ceftazidime, ceftriaxone, aztreonam, or cefepime-or resistance to the carbapenems were submitted to whole genome sequencing for identification of β-lactamases. Longitudinal and temporal trends were determined by slope coefficient. New CTX-M and OXA-1 variants were characterized.

Results: Extended-spectrum β-lactamases (ESBLs) were detected among 88.0% of the isolates that displayed elevated cephalosporin/aztreonam MICs without carbapenem resistance. bla CTX-M-15 was detected among 55.5% of the ESBL producers. ESBL rates were stable over time, but significant increases were noted among bloodstream infection and K pneumoniae isolates, mainly driven by an increase in bla CTX-M. Carbapenem resistance and carbapenemase genes were noted among 166 and 145 isolates, respectively, including 137 bla KPC, 6 bla SME, 3 bla OXA-48-like, and 3 bla NDM. Ceftazidime-avibactam and carbapenems were very active (>99% susceptibility) against ESBL producers without carbapenem resistance. Ceftazidime-avibactam inhibited 97.0% of the carbapenem-resistant isolates. This agent and meropenem-vaborbactam inhibited 96.4% and 85.0% of the 2020 isolates, respectively.

Conclusions: Overall, ESBL-producing isolates were stable, but an increase was noted for K pneumoniae isolates driven by CTX-M production. Carbapenem-resistant Enterobacterales rates decreased in the study period. The prevalence of metallo-β-lactamases and OXA-48-like remains low. Continuous surveillance of β-lactamase-producing isolates is prudent.

Keywords: ESBL; United States; carbapenemase; trends; β-lactamases.

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Conflict of interest statement

Potential conflicts of interest. JMI Laboratories contracted to perform services in 2021 for AbbVie, Affinity Biosensors, AimMax Therapeutics, Alterity Therapeutics, Amicrobe, Arietis Pharma, Armata Pharmaceuticals, Astellas Pharma, Basilea Pharmaceutica AG, Becton, Dickinson and Company, bioMérieux, Boost Biomes, Brass Dome Ventures, Bravos Biosciences, Bugworks Research, Centers for Disease Control and Prevention, Cerba Research, Cidara Therapeutics, Cipla, ContraFect, CXC7, DiamondV, Enveda Biosciences, Fedora Pharmaceuticals, Fimbrion Therapeutics, First Light Diagnostics, Forge Therapeutics, Fox Chase Cancer Center, GlaxoSmithKline, Harvard University, Institute for Clinical Pharmacodynamics, International Health Management Associates, Iterum Therapeutics, Janssen Research & Development, Johnson & Johnson, Kaleido Biosciences, Laboratory Specialists, Meiji Seika Pharma Co, Melinta Therapeutics, Menarini Group, Merck & Co, MicuRx Pharmaceuticals, Mutabilis, Nabriva Therapeutics, National Institutes of Health, Novome Biotechnologies, Omnix Medical, Paratek Pharma, Pattern Bioscience, Pfizer, Prokaryotics, Pulmocide, QPEX Biopharma, Roche Holding AG, Roivant Sciences, SeLux Diagnostics, Shionogi, Sinovent Pharmaceuticals, SNIPR Biome ApS, Spero Therapeutics, Summit Therapeutics, T2 Biosystems, TenNor Therapeutics, Thermo Fisher Scientific, University of Southern California, University of Wisconsin, US Committee on Antimicrobial Susceptibility Testing, US Food and Drug Administration, Venatorx Pharmaceutics, Weill Cornell Medicine, and Wockhardt.

Figures

Figure 1.
Figure 1.
Trend analysis of extended-spectrum β-lactamase (ESBL)–producing, CTX-M–producing, carbapenem-resistant, and Klebsiella pneumoniae carbapenem (KPC)–producing isolates collected during 2016–2020. *Statistically significant.
Figure 2.
Figure 2.
Antimicrobial activity of antimicrobial agents tested against β-lactamase–producing isolates during 2016–2020. aCarbapenemase producers not included. Abbreviation: ESBL, extended-spectrum β-lactamase.
Figure 3.
Figure 3.
Antimicrobial activity of antimicrobial agents tested against carbapenem-resistant isolates from 2020. aImipenem, piperacillin-tazobactam, and ceftriaxone displayed no activity against carbapenem-resistant isolates. *% intermediate.
See this image and copyright information in PMC

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