Breakpoints
The SIDP Podcast
7 months ago

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

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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