Activity of aztreonam-avibactam, cefiderocol, and cefepime-taniborbactam - against a global collection of genetically characterized metallo-β-lactamase-producing Enterobacterales

Sep 30, 2026

We evaluated the activity of aztreonam-avibactam and multiple comparator agents against 490 metallo-β-lactamase (MBL)-producing Enterobacterales isolates collected from 27 countries during 2019–2022. NDM-1 was the most common MBL (307 isolates), followed by NDM-5 (68) and VIM-1 (53). Aztreonam-avibactam showed universal susceptibility using EUCAST/FDA breakpoints. Resistance mechanisms and genetic backgrounds revealed diversity across species and multiple concurrent mechanisms. Aztreonam-avibactam retained activity despite additional β-lactamases and permeability or efflux-related alterations, while cefiderocol and cefepime-taniborbactam showed variable effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Methods and isolate collection (2019–2022, 27 countries)

Key MBL genes and distribution

In vitro susceptibility results for tested agents

Resistance mechanisms and genetic diversity

Background on MBL biology and clinical unmet need

| Antimicrobial Chemotherapy | Full-Length Text Activity of aztreonam-avibactam, cefiderocol, and cefepimetaniborbactam against a global collection of genetically characterized metallo-β-lactamase-producing Enterobacterales Mariana Castanheira,1 John H. Kimbrough,1 Gina M. Morgan,1 Maura Karr,1 Helio S. Sader1 AUTHOR AFFILIATION See affiliation list on p. 10. ABSTRACT We evaluated the activity of aztreonam-avibactam and comparators tested against 490 MBL-producing Enterobacterales isolates collected in 27 countries during 2019–2022. The most common MBL was NDM-1, which was detected among 307 isolates. The genes encoding NDM-5 and VIM-1 were detected among 68 and 53 isolates, respectively. Other 14 MBL-encoding genes or combinations were detected among 62 isolates. Mexico, Turkey, and Greece had the highest number of isolates (60, 59, and 57, respectively) . All isolates were susceptible to aztreonam-avibactam (MIC 50/90, 0.12/0.5 mg/L) when applying the EUCAST or FDA recently approved breakpoints (≤4 mg/L susceptible) . Cefiderocol inhibited 66.7%/90.8% of the isolates when using EUCAST/FDA breakpoints. Cefepime-taniborbactam was active against 36.7%/55.5% of the isolates using the cefepime breakpoint for comparison purposes. Tigecycline and colistin inhibited 94.1% and 76.6% of the isolates (FDA and EUCAST breakpoints, respectively) . The analysis of resistance mechanisms and genetic background of the MBL-producing isolates demonstrated genetic diversity among main species and presence of multiple resistance mechanisms including other β-lactamases, porin changes, and disruptions of efflux pump repressors. Aztreonam-avibactam was active despite the presence of these additional resistance mechanisms, but cefiderocoland cefepime-taniborbactam displayed variable activity. PBP3 YRIN and YRIK insertions were observed among 30 MBL-producing E. coli isolates. Aztreonam-avibactam MIC values ranged from 0.03 to 4 mg/L for these isolates, including an isolate carrying blaNDM-7, blaCMY-42, and porin changes. MBL-producing organisms are still considered an unmet medical need. Aztreonam-avibactam was active against this large collection of MBL-producing isolates that had elevated MIC values for many comparator agents. KEYWORDS metallo-β-lactamases, Enterobacterales, new antimicrobial agents, susceptibility, resistance mechanisms A cquired metallo-β-lactamases (MBLs) emerged in the early 1990s with the description of IMP-1 in a Serratia marcescens isolate from Japan (1) . The description of this enzyme was followed by the report of a Pseudomonas aeruginosa isolate from Verona, Italy, that produced an MBL enzyme named VIM-1 (2) . Despite the many reports of MBL-producing isolates in the literature subsequent to the description of IMP- and VIM-producing isolates, their prevalence was low and somehow limited to certain geographic areas until the late 2000s (3, 4) . This scenario changed after reports of NDM-1 in 2009 (5) . This MBL was initially described in India, but a decade after its discovery, NDM-1 became the most common MBL worldwide (6) . Isolates producing NDM have been reported on all continents, and this gene has been reported among various Gram-negative species, but mainly among Enterobacterales species (7) . Editor Boudewijn L. de Jonge, Shionogi Inc., Florham Park, New Jersey, USA Address correspondence to Mariana Castanheira, [mariana.castanheira@element.com](mariana.castanheira@element.com). 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 Pharmaceut

FAQs

How many MBL-producing Enterobacterales isolates were analyzed and over what period?

490 MBL-producing Enterobacterales isolates were collected from 27 countries during 2019–2022 and evaluated for antimicrobial activity.

Which MBL gene was most prevalent among the isolates?

NDM-1 was the most common MBL, detected among 307 of the 490 isolates.

How did aztreonam-avibactam perform against the collection compared with other agents?

All isolates were susceptible to aztreonam-avibactam using EUCAST or FDA breakpoints, while cefiderocol and cefepime-taniborbactam showed variable activity; tigecycline and colistin had different inhibition rates.

Sep 30, 2026

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