Development and Clinical Evaluation of Novel Metallo-Β-Lactamase Inhibitors

Article Sidebar

PDF HTML
Published: Mar 1, 2024
DOI: https://doi.org/10.29070/hv5vbh32
Keywords:
novel b-lactamase, avibactam, carbapenemases, clinical studies

Main Article Content

Authors

R. S. Tomar

Research Scholar, Department of Chemistry, Mewar University, Chittorgarh, Rajasthan

Dr. Prashant Kumar Sharma

Supervisor, Department of Chemistry, Mewar University, Chittorgarh, Rajasthan

Abstract

Resistant to carbapenems the very restricted treatment options for Enterobacteriaceae make them one of the most dreaded groups of infections. Three new blactamase inhibitors have been discovered to combat this danger and keep our present antimicrobial treatments going strong. Currently, clinical studies are showing promising results for the azole antibiotics the inhibitor medications avibactam, vaborbactam, and relebactam have a high affinity for Ambler class A and C blactamases. While these medicines have some fundamental commonalities, they also have some distinct distinctions that might have significant therapeutic ramifications. We take a look at the pharmacokinetics, microbiologic spectra, and important clinical studies for these new drugs. We take a look at a possible therapeutic function and some new possible combinations.

Downloads

Download data is not yet available.

Article Details

Issue

Vol. 21 No. 1 (2024): Journal of Advances in Science and Technology (JAST)

Section

Articles

References

  1. Nahar, Lutfun, Hideharu Hagiya, Kazuyoshi Gotoh, Md Asaduzzaman, and Fumio Otsuka. (2024). "New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review" Journal of Clinical Medicine 13, no. 14: 4199. https://doi.org/10.3390/jcm13144199
  2. Lee, J. H., Kim, S. G., Jang, K. M., Shin, K., Jin, H., Kim, D. W., … Lee, S. H. (2024). Elucidation of critical chemical moieties of metallo-β-lactamase inhibitors and prioritisation of target metallo-β-lactamases. Journal of Enzyme Inhibition and Medicinal Chemistry, 39(1). https://doi.org/10.1080/14756366.2024.2318830
  3. Shungube M, Hlophe AK, Girdhari L, Sabe VT, Peters BB, Reddy N, Omolabi KF, Chetty L, (2023), Synthesis and biological evaluation of novel β-lactam-metallo β-lactamase inhibitors. RSC Adv. 2023 Jun 22;13(28):18991-19001. doi: 10.1039/d3ra02490c. PMID: 37362332; PMCID: PMC10285615.
  4. Essack, S.Y. (2021), The Development of β-Lactam Antibiotics in Response to the Evolution of β-Lactamases. Pharm Res 18, 1391–1399. https://doi.org/10.1023/A:1012272403776
  5. Spyrakis, F., Santucci, M., Maso, L. et al. (2020), Virtual screening identifies broad-spectrum β-lactamase inhibitors with activity on clinically relevant serine- and metallo-carbapenemases. Sci Rep 10, 12763. https://doi.org/10.1038/s41598-020-69431-y
  6. Papp-Wallace KM, Winkler ML, Taracila MA, Bonomo RA. Variants of b-lactamase KPC-2 that are resistant to inhibition by avibactam. Antimicrob Agents Chemother. 2015;59(7):3710–7.
  7. Shields RK, Potoski BA, Haidar G, Hao B, Doi Y, Chen L, et al. Clinical outcomes, drug toxicity and emergence of ceftazidime– avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections. Clin Infect Dis. 2016;63(12):1615–8.
  8. Shields RK, Chen L, Cheng S, Chavda KD, Press EG, Snyder A, et al. Emergence of ceftazidime–avibactam resistance due to plasmid-borne blaKPC-3 mutations during treatment of carbapenem-resistant Klebsiella pneumoniae infections. Antimicrob Agents Chemother. 2017;61(3). pii: e02097-16.
  9. Sader HS, Huband MD, Castanheira M, Flamm RK. Antimicrobial susceptibility of Pseudomonas aeruginosa: results from four years (2012–2015) of the International Network for Optimal Resistance Monitoring (INFORM) Program in the United States. Antimicrob Agents Chemother. 2017;61(3). pii: e02252-16.
  10. Citron DM, Tyrrell KL, Merriam V, Goldstein EJ. In vitro activity of ceftazidime-NXL104 against 396 strains of beta-lactamase-producing anaerobes. Antimicrob Agents Chemother. 2021;55(7):3616–20.
  11. Merdjan H, Tarral A, Das S, Li J. Phase 1 study assessing the pharmacokinetic profile and safety of avibactam in patients with renal impairment. J Clin Pharmacol. 2017;57(2):211–8.
  12. Nicolau DP, Siew L, Armstrong J, Li J, Edeki T, Learoyd M, et al. Phase 1 study assessing the steady-state concentration of ceftazidime and avibactam in plasma and epithelial lining fluid following two dosing regimens. J Antimicrob Chemother. 2015;70(10):2862–9.
  13. Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother. 2023;68(5):1183–92.
  14. Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, et al. Ceftazidime–avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016;63(6):754–62.
  15. Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, et al. Ceftazidime–avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomized, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016;16(6):661–73.