PO Box 1488
Warrenville, IL 60555
Phone: 331.248.7888
Email: sidp@affinity-strategies.com
Drs. Paul Ambrose and Michael Dudley (@MikeMndudley) join Dr. Julie Ann Justo (@julie_justo) for a review of beta-lactamase inhibitor (BLI) pharmacokinetics & pharmacodynamics. They discuss factors affecting BLI’s restorative activity, the convoluted math behind establishing exposure-response relationships for BLIs, some geeky medicinal chemistry, and a little-known easter egg in the published literature.
References
- SIDP Insight on Tazobactam for ESBLs: Monogue M, et al. Pharmacotherapy. 2021 Oct;41(10):864-880. doi: 10.1002/phar.2623. PMID 34689349.
- Tazobactam with cefepime: VanScoy BD, et al. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01052-17. doi: 10.1128/AAC.01052-17. PMID: 28947475.
- Another great review of BLIs: Ambrose PG, et al. Curr Opin Pharmacol. 2017 Oct;36:86-93. doi: 10.1016/j.coph.2017.09.001. PMID: 29096172.
- Meropenem-vaborbactam target attainment: Bhavnani SM, et al. Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0213021. doi: 10.1128/aac.02130-21. PMID: 36374023.
- Meropenem-vaborbactam pulmonary exposures: Wenzler E, et al. Antimicrob Agents Chemother. 2015 Dec;59(12):7232-9. doi: 10.1128/AAC.01713-15. PMID: 26349830.
- Stand-alone BLI discussion based on CB-618: Ambrose PG, et al.. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00630-17. doi: 10.1128/AAC.00630-17. PMID: 28947474.
- NDM-9 resistance to taniborbactam: Le Terrier C, et al. Lancet Infect Dis. 2023 Apr;23(4):401-402. doi: 10.1016/S1473-3099(23)00069-5. PMID: 36796395.
- New boronate drugs and NDM: Lomovskaya O, et al. Antimicrob Agents Chemother. 2023 Aug 31:e0057923. doi: 10.1128/aac.00579-23. PMID: 37650617.
- Helpful BLI PK-PD review: Crass R, Pai MP. Pharmacotherapy. 2019 Feb;39(2):182–195. doi: 10.1002/phar.2210. PMID 30589457.
- Discovery of QPX7728 (Xeruborbactam): Hecker SJ, et al. J Med Chem. 2020 Jul 23;63(14):7491-7507. doi: 10.1021/acs.jmedchem.9b01976. PMID 32150407.
- Xeruborbactam binding to PBPs directly: Lomovskaya O, et al. Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0216821. doi: 10.1128/AAC.02168-21. PMID: 34902261.
- Xeruborbactam predicted best by fAUC/MIC with oral ceftibuten: Tarazi Z, et al. Open Forum Infect Dis. Volume 9, Issue Supplement_2, December 2022, ofac492.666, https://doi.org/10.1093/ofid/ofac492.666 (Poster 614)
- Xeruborbactam predicted best by fAUC/MIC with meropenem: Tarazi Z, et al. Open Forum Infect Dis. Volume 9, Issue Supplement_2, December 2022, ofac492.667, https://doi.org/10.1093/ofid/ofac492.667 (Poster 615)
- First 2013 AAC paper on tazobactam with ceftolozane from Ambrose group: VanScoy B, et al. Antimicrob Agents Chemother. 2013 Jun;57(6):2809-14. doi: 10.1128/AAC.02513-12. PMID: 23629705.
- Second 2013 AAC paper on tazobactam with ceftolozane from Ambrose group: Vanscoy B, et al. Antimicrob Agents Chemother. 2013 Dec;57(12):5924-30. doi: 10.1128/AAC.00656-13. PMID: 24041895.
- Electric Telescope, 52 Class 530 Series 1080p LCD/HD; Samsung Group, Seoul, South Korea, available at: https://www.samsung.com/ca/support/model/LN52C530F1FXZC/
- Tazobactam with Piperacillin from Ambrose group: Nicasio AM, et al. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2075-80. doi: 10.1128/AAC.02747-15. PMID: 26787689.
Paul Ambrose, PharmD, FIDSA
Dr. Paul Ambrose is the president of the Institute for Clinical Pharmacodynamics. He has worked in drug development for over 25 years and heavily focuses on anti-infective translational science and pharmacokinetic-pharmacodynamic principles. He is also sits on the executive committee of The United States Committee on Antimicrobial Susceptibility Testing
Mike Dudley, PharmD
Dr. Mike Dudley is the President and CEO of Qpex Biopharma. Mike has more than 40 years of experience in anti-infective research, development and commercialization. He is a fellow of the Infectious Diseases Society of America (FIDSA). Prior to his career in industry, Mike held academic appointments at the University of Rhode Island College of Pharmacy and Brown University School of Medicine in Providence, Rhode Island. He has published more than 160 scientific papers and book chapters on the discovery, preclinical/clinical evaluation and use of anti-infectives. Mike completed undergraduate work in biology at Pepperdine University in Malibu, California. He earned a Doctor of Pharmacy and completed his residency at the University of California, San Francisco (UCSF). Mike completed a fellowship in infectious disease at Hartford Hospital in Hartford, Connecticut.
