New Delhi metallo-β-lactamase (NDM-1): an update

Area of Science:

• Microbiology
• Molecular Biology
• Antimicrobial Resistance

Background:

• New Delhi metallo-β-lactamase (NDM-1) is a significant carbapenemase.
• NDM-1 producers often exhibit resistance to all β-lactams due to co-produced aztreonam-hydrolyzing enzymes.
• The bla(NDM-1) gene encodes a distinct 269-amino acid protein with limited homology to other metallo-β-lactamases.

Purpose of the Study:

• To provide an updated review of the scientific literature on NDM-1.
• To propose a therapeutic strategy against NDM-1 producing pathogens.
• To recommend surveillance for specific antibiotic combinations.

Main Methods:

• Literature review of NDM-1 enzyme and resistance mechanisms.
• Analysis of enzyme characteristics and genetic information.
• Proposal of a combination therapy strategy based on existing literature and expert recommendations.

Main Results:

• NDM-1 inactivates most β-lactams, but aztreonam remains active.
• Co-production of aztreonamases leads to pan-β-lactam resistance.
• Limited sequence identity of NDM-1 to other metallo-β-lactamases (e.g., VIM-1/VIM-2 at 32.4%).

Conclusions:

• A combination of aztreonam and a versatile inhibitor targeting prevalent aztreonamases is a potential strategy against NDM-1 producers.
• Surveillance studies evaluating the aztreonam/NXL-104 combination are strongly recommended globally.