Rising Threat of Metallo-β-Lactamases Drives Demand for Novel Therapeutics

Metallo-β-lactamases (MβLs), including New Delhi metallo-β-lactamase (NDM), continue to emerge as a growing antimicrobial resistance threat worldwide, according to Emily Heil, PharmD, MS, FIDP, BCIDP, AAHIVP, professor in the Department of Practice, Sciences, and Health Outcomes Research at the University of Maryland School of Pharmacy. She also serves as the pharmacy director of the Antimicrobial Stewardship Program at the University of Maryland Medical Center. Heil spoke about this topic during the recent MAD-ID and SIDP 2026 annual meeting. Although serine β-lactamases such as Klebsiella pneumoniae carbapenemase remain more common in the United States, Heil emphasized that clinicians are seeing a steady rise in MβL-producing organisms, making rapid and specific carbapenemase detection increasingly important for guiding treatment decisions.

“Over the last few years, we have seen a distinct rise in our MβLs, so they are still far and away the least common kind of set of β-lactamases that we see in the United States, but they are on the rise, specifically the NDM or New Delhi metallo-β-lactamase,” Heil said.

New Combination Therapies Offer Hope Against MβL Resistance

Heil explained that therapeutic strategies for MβL infections are rapidly evolving as new agents enter the market. One key advancement is the combination of aztreonam and avibactam, which leverages aztreonam’s stability against MβL hydrolysis while avibactam protects against serine β-lactamases. She noted that when ceftazidime-avibactam is paired with aztreonam as an alternative strategy, simultaneous prolonged infusions are critical to maximize pharmacokinetic and pharmacodynamic success.

“That's the best way that they're going to see that optimal activity,” Heil said.

Heil also highlighted promising investigational agents, including cefepime-zidebactam and cefiderocol combinations with novel β-lactamase inhibitors, which may expand future treatment options for highly resistant NDM-producing pathogens.