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Antimicrobial activities of aztreonam-avibactam and comparator agents tested against Enterobacterales from European hospitals analysed by geographic region and infection type (2019–2020)

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Abstract

The purpose of this study is to evaluate the activities of aztreonam-avibactam and comparator agents against Enterobacterales isolates from European medical centres as well as the occurrence of carbapenemases (CPEs). A total of 11,655 Enterobacterales isolates were collected consecutively in 2019–2020 from 38 medical centres located in Western Europe (W-EU; n = 8,784; 25 centres in 10 countries) and the Eastern European and Mediterranean region (E-EU; n = 2,871; 13 centres in 10 countries). Isolates were susceptibility tested by broth microdilution methods in a monitoring laboratory. The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by geographic region and infection type. Isolates that showed resistance to carbapenems (CRE) and/or elevated MICs (> 8 mg/L) for aztreonam-avibactam were screened for β-lactamase-encoding genes by whole-genome sequencing. Aztreonam-avibactam inhibited 99.9% of Enterobacterales at ≤ 8 mg/L (MIC50/90, ≤ 0.03/0.12 mg/L) and retained potent activity against CRE (MIC50/90, 0.25/0.5 mg/L), multidrug-resistant isolates (MDR; MIC50/90, 0.12/0.5 mg/L), and extensively drug-resistant (XDR) isolates (MIC50/90, 0.25/0.5 mg/L). Susceptibility to comparator agents was consistently lower among isolates from E-EU compared to W-EU for all infection types evaluated. CRE rates varied from 0.6% (urinary tract infection [UTI]) to 2.3% (bloodstream infection) in W-EU, and from 6.1% (UTI) to 17.0% (pneumonia) in E-EU. A CPE-encoding gene was identified in 360 of 424 (84.9%) CRE isolates, and the most common CPEs were blaKPC (36.3% of CRE), blaOXA-48 type (27.1% of CRE), and the MBLs (25.7% of CRE). All CPE producers were inhibited at an aztreonam-avibactam concentration of ≤ 8 mg/L. Aztreonam-avibactam demonstrated potent activity across the evaluated geographic regions and infection types.

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Acknowledgements

The authors thank all participants of the SENTRY Antimicrobial Surveillance Program for their work in providing isolates. Editorial support was provided by Amy Chen and Judy Oberholser at JMI Laboratories and was funded by Pfizer.

Funding

This study was supported by Pfizer Inc. Helio S. Sader, Rodrigo E. Mendes, S. J. Ryan Arends, Cecilia G. Carvalhaes, and Mariana Castanheira are employees of JMI Laboratories, which was a paid consultant to Pfizer in connection with the development of this manuscript.

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  1. JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA, 52317, USA

    Helio S. Sader, Rodrigo E. Mendes, S. J. Ryan Arends, Cecilia G. Carvalhaes & Mariana Castanheira

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  1. Helio S. Sader
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  2. Rodrigo E. Mendes
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Correspondence to Helio S. Sader.

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JMI Laboratories contracted to perform services in 2018–2021 for Achaogen, Inc., Affinity Biosensors, Albany College of Pharmacy and Health Sciences, Allecra Therapeutics, Allergan, Amicrobe Advanced Biomaterials, Inc., American Proficiency Institute, AmpliPhi Biosciences Corp., Amplyx Pharma, Antabio, Arietis Corp., Arixa Pharmaceuticals, Inc., Artugen Therapeutics USA, Inc., Astellas Pharma Inc., Athelas, Becton, Basilea Pharmaceutica Ltd., Bayer AG, Becton, Beth Israel Deaconess Medical Center, BIDMC, bioMerieux, Inc., bioMerieux SA, BioVersys Ag, Boston Pharmaceuticals, Bugworks Research Inc., CEM-102 Pharmaceuticals, Cepheid, Cidara Therapeutics, Inc., Cipla, Contrafect, Cormedix Inc., Crestone, Inc., Curza, CXC7, DePuy Synthes, Destiny Pharma, Dickinson and Company, Discuva Ltd., Dr. Falk Pharma GmbH, Emery Pharma, Entasis Therapeutics, Eurofarma Laboratorios SA, Fedora Pharmaceutical, F. Hoffmann-La Roche Ltd., Fimbrion Therapeutics, US Food and Drug Administration, Fox Chase Chemical Diversity Center, Inc., Gateway Pharmaceutical LLC, GenePOC Inc., Geom Therapeutics, Inc., GlaxoSmithKline plc, Guardian Therapeutics, Hardy Diagnostics, Harvard University, Helperby, HiMedia Laboratories, ICON plc, Idorsia Pharmaceuticals Ltd., IHMA, Iterum Therapeutics plc, Janssen Research & Development, Johnson & Johnson, Kaleido Biosciences, KBP Biosciences, Laboratory Specialists, Inc., Luminex, Matrivax, Mayo Clinic, Medpace, Meiji Seika Pharma Co., Ltd., Melinta Therapeutics, Inc., Menarini, Merck & Co., Inc., Meridian Bioscience Inc., Micromyx, Microchem Laboratory, MicuRx Pharmaceutics, Inc., Mutabilis Co., N8 Medical, Nabriva Therapeutics plc, National Institutes of Health, NAEJA-RGM, National University of Singapore, North Bristol NHS Trust, Novartis AG, Novome Biotechnologies, Oxoid Ltd., Paratek Pharmaceuticals, Inc., Pfizer, Inc., Pharmaceutical Product Development, LLC, Polyphor Ltd., Prokaryotics Inc., QPEX Biopharma, Inc., Ra Pharmaceuticals, Inc., Rhode Island Hospital, RIHML, Roche, Roivant Sciences, Ltd., Safeguard Biosystems, Salvat, Scynexis, Inc., SeLux Diagnostics, Inc., Shionogi and Co., Ltd., SinSa Labs, Specific Diagnostics, Spero Therapeutics, Summit Pharmaceuticals International Corp., SuperTrans Medical LT, Synlogic, T2 Biosystems, Taisho Pharmaceutical Co., Ltd., TenNor Therapeutics Ltd., Tetraphase Pharmaceuticals, The Medicines Company, The University of Queensland, Theravance Biopharma, Thermo Fisher Scientific, Tufts Medical Center, Universite de Sherbrooke, University of Colorado, University of Southern California-San Diego, University of Iowa, University of Iowa Hospitals and Clinics, University of North Texas Health Science Center, University of Wisconsin, UNT System College of Pharmacy, URMC, UT Southwestern, VenatoRx, Viosera Therapeutics, Vyome Therapeutics Inc., Wayne State University, Wockhardt, Yukon Pharmaceuticals, Inc., Zai Lab, and Zavante Therapeutics, Inc. There are no speakers’ bureaus or stock options to declare.

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Sader, H.S., Mendes, R.E., Arends, S.J.R. et al. Antimicrobial activities of aztreonam-avibactam and comparator agents tested against Enterobacterales from European hospitals analysed by geographic region and infection type (2019–2020). Eur J Clin Microbiol Infect Dis 41, 477–487 (2022). https://doi.org/10.1007/s10096-022-04400-z

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