Aztreonam-Avibactam Holds Activity as MBL-Producing CRE Rise in US

Aztreonam-avibactam (Emblaveo; AbbVie) inhibited 97.7% of metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) from US medical centers, as MBL producers more than doubled their share of CRE between 2021 and 2025.¹ Helio S. Sader, MD, PhD, of Element Iowa City (JMI Laboratories), presented the surveillance data at IDWeek 2026, held October 21-24 in Washington, DC. Two posters from India reported weaker activity against carbapenem-resistant Escherichia coli and NDM-producing Pseudomonas aeruginosa.^2,3

The FDA approved aztreonam-avibactam in February 2025, and the combination has shown potent activity against MBL-producing Enterobacterales.¹ Rising MBL prevalence has narrowed options for CRE in US hospitals, a central challenge in antimicrobial resistance management.¹

US Surveillance of Aztreonam-Avibactam Activity Against CRE by Resistance Mechanism

The investigators tested 514 CRE isolates collected consecutively from 67 US medical centers from 2021 to 2025, defining CRE as resistant to meropenem or imipenem at an MIC of 4 mg/L or higher.¹ Whole-genome sequencing was performed on all isolates to screen for β-lactamases and characterize resistance mechanisms, and results were stratified by year and carbapenemase type.¹

Aztreonam-avibactam was the most active agent overall (MIC50/90, 0.25/1 mg/L), with yearly susceptibility from 94.2% in 2024 to 100% in 2023.¹ Cefiderocol susceptibility ranged from 91.8% in 2025 to 95.5% in 2022.¹ Both agents held activity regardless of the carbapenem resistance mechanism, unlike the other β-lactamase inhibitor combinations tested.¹

The share of MBL producers among CRE climbed from 20.4% in 2021 to 48.6% in 2025, while KPC producers declined from 56.1% to 30.1%.¹ Against MBL producers, only aztreonam-avibactam (97.7% susceptible; MIC50/90, 0.12/1 mg/L) and cefiderocol (85.6%; MIC50/90, 2/8 mg/L) retained good activity.¹

As a result, the activity of ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam fell markedly over the study period.¹ All β-lactamase inhibitor combinations and cefiderocol remained potent against KPC producers.¹

The authors attributed the declines to the growing share of MBL producers rather than to changes within each genotype.¹ They called for comprehensive surveillance to guide therapy and infection control as resistance mechanisms shift, given how quickly the epidemiology of β-lactam resistance is moving.¹

Aztreonam-Avibactam Gaps in Carbapenem-Resistant E coli and NDM-Producing P aeruginosa

At 3 sites in India within the CDC Global Action in Healthcare Network, investigators tested 116 carbapenem-resistant E coli and 140 carbapenem-resistant Klebsiella pneumoniae isolates.² Aztreonam-avibactam was active against 100% of K pneumoniae isolates but only 52% of E coli isolates (P < .001). Cefiderocol showed a similar species gap (93% vs 69%; P = .007), whereas plazomicin was more active against E coli (62% vs 29%).²

Susceptibility also varied by carbapenemase genotype.² Among 71 NDM-producing E coli isolates, aztreonam-avibactam was active against 49%, compared with 100% of 32 NDM-producing K pneumoniae isolates.²

Ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam were active against 1% or fewer NDM-producing E coli isolates.² Against OXA-48-like producers, most agents performed better, with ceftazidime-avibactam active against 86% of K pneumoniae isolates.²

Among 115 NDM-producing P aeruginosa isolates from 6 tertiary hospitals in India, aztreonam-avibactam inhibited 40.9% at 8 mg/L or lower with avibactam at 4 mg/L, rising to 64.3% with avibactam at 8 mg/L.³ Aztreonam paired with relebactam or vaborbactam inhibited roughly 10% or fewer.³

First-line agents including cefepime, meropenem, imipenem, amikacin, and ciprofloxacin had MIC50 and MIC90 values above 64 mg/L.³ Aztreonam alone inhibited 8.7% of isolates at 8 mg/L or lower, and meropenem and imipenem inhibited none at their breakpoints.³

The authors attributed the limited activity to overexpressed efflux pumps in P aeruginosa, which can render β-lactamase inhibitor pairings ineffective against nonenzymatic resistance.³ Cefepime-zidebactam inhibited all 115 isolates at its investigational breakpoint of 64 mg/L. The study included a coauthor from Wockhardt, which develops cefepime-zidebactam, and AbbVie, which markets aztreonam-avibactam in the US, had a coauthor on the US surveillance poster.^1,3

References

1. Sader HS, Papp-Wallace KM, Debabov D, Kimbrough JH, Castanheira M. Aztreonam-avibactam activity against carbapenem-resistant Enterobacterales from United States medical centers stratified by year and resistance mechanism (2021-2025). Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-6.

2. Basu S, Kambli P, Singh S, et al. Comparative in vitro activity of novel antimicrobials against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae from three sites in India. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-30.

3. Shindikar A, Mahesh R, Phute S, et al. Activity of aztreonam combined with avibactam or relebactam or vaborbactam against NDM-producing Pseudomonas aeruginosa collected from tertiary hospitals in India. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-26.