Emblaveo Potent Against Difficult-to-Treat Enterobacterales

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The antibiotic aztreonam-avibactam (Emblaveo, AbbVie) maintains good activity against antimicrobial-resistant organisms, outperforming other agents against difficult-to-treat resistant (DTR) Enterobacterales, as well as Enterobacterales resistant to other drugs, in isolates from U.S. medical centers, according to a trio of posters presented at IDWeek 2025, in Atlanta.

“The results were consistent with previous data and highlight aztreonam-avibactam’s in vitro activity,” said Todd Riccobene, PhD, the senior scientific director of anti-infectives and infectious diseases at AbbVie. The drug “was specifically designed to have activity against some of the most resistant gram-negative bacteria, including metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).”

Testing Drug Potency

In the first study (abstract P-1316), investigators analyzed 42,295 Enterobacterales isolates collected from 85 U.S. medical centers for the 2020-2024 period. The collection included 450 CRE and 307 DTR isolates, screened for beta-lactamases by whole-genome sequencing.

Aztreonam-avibactam was active (minimum inhibitory concentration [MIC] =4 mg/L) against 98% of DTR (MIC_50/90, 0.25/1 mg/L) and 97.1% of CRE (MIC_50/90, 0.25/1 mg/L) isolates, and retained potent activity against DTR isolates nonsusceptible (NS) to ceftazidime-avibactam (Avycaz, AbbVie) (95.5% susceptible; MIC_50/90, 0.25/1 mg/L), meropenem-vaborbactam (Vabomere, Melinta) (96.2% susceptible; MIC_50/90, 0.25/1 mg/L), and cefiderocol (Fetroja, Shionogi) (90% susceptible; MIC_50/90, 0.5/4 mg/L). Cefiderocol was active against 93.5% of DTR isolates, where the other agents exhibited limited activity. Aztreonam-avibactam and cefiderocol were active against 97.7% and 86.4% of MBL producers, respectively.

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Similar findings were seen in a second study (abstract P-1319), where aztreonam-avibactam preformed well against isolates NS to ceftazidime-avibactam, meropenem-vaborbactam, and MBL producers. A third study (abstract P-1320) found that while the drug maintained potent activity against Stenotrophomonas maltophilia, other agents performed better against the pathogen.

More Research Needed

Appropriate assessment of breakpoints for these organisms is urgently needed to provide better guidance of antimicrobial therapy for these infections, the authors wrote.

The percentage of CRE that produces MBLs “has been increasing dramatically across the U.S. in recent years [Ann Intern Med 2025;178(12):1818-1821],” Dr. Riccobene said, and has begun to compromise the activity of some newer agents.

“The thing that is extremely striking to me is the disconnect between cefiderocol and aztreonam-avibactam, where aztreonam-avibactam is in some cases almost 15% better,” commented James S. Lewis II, PharmD, the clinical supervisor for infectious disease at Oregon Health & Science University, in Portland. Mechanistically, he said he would like a better understanding of what is happening in these isolates. “Are these mechanisms we would have expected, or are we seeing something that is emerging here? What is driving that 15% delta?”

The studies were sponsored by AbbVie. Dr. Lewis reported that he had served as a consultant to AbbVie during Emblaveo’s development and has served as a consultant to Shionogi. Dr. Riccobene reported no relevant financial disclosures beyond his employment.