#86 – The Robin to Your Batman: Ensuring Adequate Beta-lactamase Inhibitor Exposure to Restore Beta-lactam Activity

#86 – The Robin to Your Batman: Ensuring Adequate Beta-lactamase Inhibitor Exposure to Restore Beta-lactam Activity

Author: Society of Infectious Diseases Pharmacists October 20, 2023 Duration: 1:19:32
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Episode Notes

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.

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References

  1. SIDP Insight on Tazobactam for ESBLs: Monogue M, et al. Pharmacotherapy. 2021 Oct;41(10):864-880. doi: 10.1002/phar.2623. PMID 34689349.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. New boronate drugs and NDM: Lomovskaya O, et al. Antimicrob Agents Chemother. 2023 Aug 31:e0057923. doi: 10.1128/aac.00579-23. PMID: 37650617.
  9. Helpful BLI PK-PD review: Crass R, Pai MP. Pharmacotherapy. 2019 Feb;39(2):182–195. doi: 10.1002/phar.2210. PMID 30589457.
  10. 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.
  11. 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.
  12. 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)
  13. 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)
  14. 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.
  15. 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.
  16. Electric Telescope, 52 Class 530 Series 1080p LCD/HD; Samsung Group, Seoul, South Korea, available at: https://www.samsung.com/ca/support/model/LN52C530F1FXZC/
  17. 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.

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Hosted by the Society of Infectious Diseases Pharmacists, Breakpoints is a podcast dedicated to the intricate and ever-evolving world of antimicrobial therapy. Each episode delves into the practical challenges and scientific nuances faced by pharmacists on the front lines of patient care, from interpreting susceptibility data and optimizing dosing strategies to navigating the complexities of antimicrobial stewardship. The conversations in this podcast bridge the gap between groundbreaking infectious diseases research and its direct application in clinical settings, offering insights that are both academically rigorous and immediately useful. You’ll hear expert discussions on new resistance patterns, evolving treatment guidelines, and the real-world implementation of life-saving protocols. Designed for healthcare professionals committed to precision medicine, Breakpoints provides a deeper understanding of how to effectively manage infections and improve patient outcomes. Tune in for thoughtful analysis and forward-thinking dialogue that defines the critical role of specialized pharmacists in public health.
Author: Language: en-us Episodes: 100

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