Using Enzyme Inhibitors to Assess the Potential for Antimicrobial Resistance

Early tests revealed that MK-3402, an experimental metallo-beta-lactamase inhibitor, was well tolerated after administration to healthy individuals. The trials were carried out by researchers at Merck in partnership with researchers at Ghent University Hospital in Belgium.

Additional clinical trials are required to assess the potential of intravenous MK-3402 for usage in combination with other drugs to treat bacterial infections that are resistant to antibiotics. The results will be presented at ASM Microbe 2023, the American Society for Microbiology’s annual meeting.

The public's health is seriously threatened by antimicrobial resistance. Since they manufacture the metallo-beta-lactamase enzyme, some bacteria are immune to therapy, rendering the beta-lactam class of antibiotics ineffective.

When used in conjunction with an antibacterial drug (and another type of blocking drug against other types of beta-lactamase enzymes produced by bacteria), K-3402 is made to block metallo-beta-lactamase enzymes, allowing the antibacterial drugs to still be effective against bacteria that are otherwise resistant.

MK-3402 and a placebo were the subjects of two experiments, each of which used a different dosage and number of doses. Participants and study staff were unaware of who was getting the trial medicine and who was receiving a placebo.

Blood tests, electrocardiograms, blood pressure, heart rate, temperature, breathing rate, and participant-reported adverse effects findings were all checked to ensure safety.

The MK-3402 blood levels determined in these trials will aid in the development of a dosage regimen that should deliver sufficient MK-3402 blood levels to inhibit bacterial metallo-beta-lactamase. However, a more thorough analysis of MK-3402’s safety and efficacy in combination with other antibacterial medications is required.