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. 2025 May 27;14(6):544.
doi: 10.3390/antibiotics14060544.

Activity of β-Lactamase Inhibitor Combinations Against Enterobacterales Isolated from Patients with Intra-Abdominal Infection from United States Medical Centres (2019-2023)

Helio S Sader  1 , John H Kimbrough  1 , Marisa L Winkler  1 , Rodrigo E Mendes  1 , Mariana Castanheira  1
Affiliations

Activity of β-Lactamase Inhibitor Combinations Against Enterobacterales Isolated from Patients with Intra-Abdominal Infection from United States Medical Centres (2019-2023)

Helio S Sader et al. Antibiotics (Basel). .

Abstract

Objective: To evaluate the antimicrobial susceptibility of Enterobacterales isolated from patients with intra-abdominal infections (IAI) in United States (US) medical centres. Methods: A total of 2036 isolates (1/patient) were consecutively collected from patients with IAI in 63 US hospitals in 2019-2023 and susceptibility tested by broth microdilution. Carbapenem-resistant Enterobacterales (CRE) were screened for carbapenemases by whole genome sequencing. Results: The most common Enterobacterales species were E. coli (47.1%), K. pneumoniae (18.7%), and E. cloacae species complex (9.8%). The most active agents were aztreonam-avibactam (MIC50/90, ≤0.03/0.12 mg/L), ceftazidime-avibactam (MIC50/90, 0.12/0.25 mg/L), and meropenem-vaborbactam (MIC50/90, 0.03/0.06 mg/L) with 99.9% susceptibility. A multidrug-resistant (MDR) phenotype (nonsusceptibility to ≥3 classes) was observed in 21.4% of Enterobacterales (n = 436). Piperacillin-tazobactam was active against 87.2% of Enterobacterales overall and 50.2% of MDR isolates, and meropenem was active against 99.2% of Enterobacterales and 96.1% of MDR isolates. Only 51.6% of Enterobacterales were susceptible to ampicillin-sulbactam. An acquired broad-spectrum β-lactamase gene was identified in 207 (10.2%) isolates and included extended-spectrum β-lactamases (ESBL; n = 182), transferable AmpC (n = 24) and carbapenemases (n = 9). Eight isolates produced two β-lactamase classes. Conclusions: Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam exhibited almost complete activity (99.9% susceptibility) against Enterobacterales causing IAI in US hospitals. In contrast, piperacillin-tazobactam exhibited limited activity against these organisms, especially those with a MDR phenotype.

Keywords: CRE; MDR; antimicrobial resistance; aztreonam-avibactam; beta-lactamase inhibitor combination; carbapenem-resistant Enterobacterales.

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Conflict of interest statement

None of the authors has a conflict of interest. Element Iowa City (JMI Laboratories) was contracted to perform services in 2022–2024 for AimMax Therapeutics, Amicrobe, Inc., Appili Therapeutics, Armata Pharmaceuticals, Astellas Pharma, Inc., Basilea Pharmaceutica AG, Biosergen AB, Bugworks, Cerba Research NV, Cidara Therapeutics, Cipla USA Inc., ContraFect Corporation, CorMedix Inc., Crestone, Inc., Curza Global, LLC, Diamond V, Discuva Ltd., Entasis Therapeutics, Enveda Biosciences, Evopoint Biosciences, Fedora Pharmaceuticals, Fox Chase Chemical Diversity Center, Genentech, Gilead Sciences, Inc., GSK plc, Iterum Therapeutics plc, Janssen Biopharma, Johnson & Johnson, Kaleido Biosciences, LifeMine Therapeutics, Medpace, Inc, Lysovant Sciences, Inc, Meiji Seika Pharma, Melinta Therapeutics, Menarini Group, Merck & Co., MicuRx Pharmaceutical Inc., Mundipharma International Ltd., Mutabilis, Nabriva Therapeutics, National Cancer Institute, National Institutes of Health, Ohio State University, Omnix Medical Ltd., Paratek Pharmaceuticals, Pfizer, PolyPid Ltd., PPD, Prokaryotics, Inc., Pulmocide Ltd., Qpex Biopharma, Revagenix, Roche Holding AG, Roivant Sciences, Scynexis, Inc., Shionogi & Co., Ltd., Sinovent Pharmaceuticals, Inc., Spero Therapeutics, Sumitovant Biopharma, Inc., TenNor Therapeutics, U.S. Food and Drug Administration, VenatoRx Pharmaceuticals, Washington University, Watershed Medical, LLC, Wockhardt, and Zoetis, Inc.

Figures

Figure 1
Figure 1
Yearly trend of Enterobacterales (n = 2036) susceptibility to selected antimicrobial agents.
See this image and copyright information in PMC

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