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Gram-negative resistance is beautifully intricate, scientifically elegant, and very complex. Nothing is more exciting than the recently approved and bursting pipeline of beta-lactamase inhibitors. Listen to Drs. Sam Aitken and Christophe Le Terrier, along with host Dr. Erin McCreary, describe the nuanced enzymology and other antibacterial properties of beta-lactamase inhibitors. This episode also discusses the concepts of stand-alone inhibitors, resistance development, and more. If you want to learn more about sulbactam, clavulanic acid, tazobactam, avibactam, relebactam, vaborbactam, durlobactam, enmetazobactam, zidebactam, nacubactam, ledaborbactam, taniborbactam, and xeruborbactam – this episode is for you!
Funding for this podcase was provided by Shionogi Inc
References:
1. Le Terrier C, Nordmann P, Buchs C, et al. Wide dissemination of Gram-negative bacteria producing the taniborbactam-resistant NDM-9 variant: a One Health concern. J Antimicrob Chemother. 2023;78(9):2382-2384. doi:10.1093/jac/dkad210
2. Le Terrier C, Nordmann P, Buchs C, Poirel L. Effect of modification of penicillin-binding protein 3 on susceptibility to ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and cefiderocol of Escherichia coli strains producing broad-spectrum β-lactamases. Antimicrob Agents Chemother. 2024;68(4):e0154823. doi:10.1128/AAC.01548-23
3. Le Terrier C, Freire S, Viguier C, Findlay J, Nordmann P, Poirel L. Relative inhibitory activities of the broad-spectrum β-lactamase inhibitor xeruborbactam in comparison with taniborbactam against metallo-β-lactamases produced in Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2024;68(6):e0157023. doi:10.1128/AAC.01570-23
4. Le Terrier C, Mlynarcik P, Sadek M, Nordmann P, Poirel L. Relative inhibitory activities of newly developed diazabicyclooctanes, boronic acid derivatives, and penicillin-based sulfone β-lactamase inhibitors against broad-spectrum AmpC β-lactamases. Antimicrob Agents Chemother. 2024;68(11):e0077524. doi:10.1128/AAC.00775-24
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guests
Christophe Le Terrier, MD, PhD, is an intensive care physician and researcher in medical and molecular microbiology in Switzerland. His research focuses on antimicrobial resistance, particularly carbapenemase-producing Gram-negative bacteria, novel β-lactam/β-lactamase inhibitor combinations, and emerging resistance mechanisms. He contributed to the characterization of resistance mechanisms affecting several next-generation β-lactamase inhibitors, including taniborbactam, zidebactam, and xeruborbactam and he is particularly interested in bridging molecular microbiology and critical care medicine to improve the management of multidrug-resistant infections.
Dr. Aitken is a Clinical Pharmacist Specialist in Infectious Diseases at Michigan Medicine, Adjunct Clinical Professor of Pharmacy at The University of Michigan College of Pharmacy, and Adjunct Clinical Professor of Infectious Diseases at the University of Michigan Medical School. Dr. Aitken’s clinical practice is focused on immunocompromised infectious diseases and his research is focused on gaining an understanding of the mechanisms, epidemiology, and treatment of mutidrug-resistant bacterial infections. Dr. Aitken enjoys most foods and travel destinations that would be highlighted in a good infectious diseases consult note.
