Novel Macrolide Antibiotic Nafithromycin for Tackling Emerging Resistance in Respiratory Pathogens Encountered in India.

IF 2.6 3区 生物学 Q3 MICROBIOLOGY
Swati Paliwal, Kajal Chaudhary, Uma Agarwal, Rajiv Kumar Tonk
{"title":"Novel Macrolide Antibiotic Nafithromycin for Tackling Emerging Resistance in Respiratory Pathogens Encountered in India.","authors":"Swati Paliwal, Kajal Chaudhary, Uma Agarwal, Rajiv Kumar Tonk","doi":"10.1007/s00284-025-04455-z","DOIUrl":null,"url":null,"abstract":"<p><p>Nafithromycin (WCK 4873), is India's first approved macrolide antibiotic by DCGI(Drug Controller General of India), represents a significant advancement in combating antimicrobial resistance (AMR) and multidrug-resistant (MDR) pathogens. After three decades of research and development, supported by BIRAC, Wockhardt Ltd. successfully developed this innovative lactone- ketolide antibiotic which demonstrates superior efficacy against respiratory pathogens, particularly drug-resistant Streptococcus pneumoniae. Its unique structural modifications at the C-3 position and enhanced side chain configurations improve its pharmacological profile compared to previous generation macrolides. Nafithromycin binds to both domains II and V of 23 s rRna, thereby circumventing the resistance mechanisms which impacts older macrolide due to their single target binding. Owing to dual binding of nafithromycin, it is more potent than the older macrolides. Additionally, nafithromycin exhibits immunomodulatory effects in acute lung injury models, suggesting potential therapeutic benefits beyond its antimicrobial activity. Moreover, Phase I and II trials demonstrate its safety and tolerability, with minimal drug-drug interactions due to reduced CYP3A4/5 inhibition. Phase III results show that nafithromycin is effective against a wide variety of respiratory infections as well as intracellular atypical pathogens which can be difficult to treat other ways. No significant AEs were encountered. In this comprehensive review, the adverse effects of other antibiotics are examined, along with the benefits of nafithromycin over other medications, its development, mechanism of action, structure-activity relationships, clinical efficacy, drug delivery strategies via various routes to overcome antimicrobial resistance, strategies to combat antimicrobial resistance, and future perspectives in addressing the global antimicrobial resistance challenges.</p>","PeriodicalId":11360,"journal":{"name":"Current Microbiology","volume":"82 10","pages":"465"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s00284-025-04455-z","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Nafithromycin (WCK 4873), is India's first approved macrolide antibiotic by DCGI(Drug Controller General of India), represents a significant advancement in combating antimicrobial resistance (AMR) and multidrug-resistant (MDR) pathogens. After three decades of research and development, supported by BIRAC, Wockhardt Ltd. successfully developed this innovative lactone- ketolide antibiotic which demonstrates superior efficacy against respiratory pathogens, particularly drug-resistant Streptococcus pneumoniae. Its unique structural modifications at the C-3 position and enhanced side chain configurations improve its pharmacological profile compared to previous generation macrolides. Nafithromycin binds to both domains II and V of 23 s rRna, thereby circumventing the resistance mechanisms which impacts older macrolide due to their single target binding. Owing to dual binding of nafithromycin, it is more potent than the older macrolides. Additionally, nafithromycin exhibits immunomodulatory effects in acute lung injury models, suggesting potential therapeutic benefits beyond its antimicrobial activity. Moreover, Phase I and II trials demonstrate its safety and tolerability, with minimal drug-drug interactions due to reduced CYP3A4/5 inhibition. Phase III results show that nafithromycin is effective against a wide variety of respiratory infections as well as intracellular atypical pathogens which can be difficult to treat other ways. No significant AEs were encountered. In this comprehensive review, the adverse effects of other antibiotics are examined, along with the benefits of nafithromycin over other medications, its development, mechanism of action, structure-activity relationships, clinical efficacy, drug delivery strategies via various routes to overcome antimicrobial resistance, strategies to combat antimicrobial resistance, and future perspectives in addressing the global antimicrobial resistance challenges.

新型大环内酯类抗生素纳红霉素用于解决印度呼吸道病原体新出现的耐药性。
Nafithromycin (WCK 4873)是印度首个获得印度药品监督管理局(DCGI)批准的大环内酯类抗生素,代表着在抗击抗菌素耐药性(AMR)和多重耐药(MDR)病原体方面取得的重大进展。在BIRAC的支持下,经过三十年的研究和开发,Wockhardt有限公司成功开发出这种创新的内酯酮内酯抗生素,对呼吸道病原体,特别是耐药肺炎链球菌具有卓越的疗效。与上一代大环内酯相比,其在C-3位置的独特结构修饰和增强的侧链构型改善了其药理学特征。Nafithromycin结合23s rRna的结构域II和V,从而绕过了由于单靶标结合而影响旧大环内酯类药物的耐药机制。由于非红霉素的双重结合,它比旧的大环内酯类药物更有效。此外,非红霉素在急性肺损伤模型中表现出免疫调节作用,表明其潜在的治疗益处超出其抗菌活性。此外,I期和II期试验证明了其安全性和耐受性,由于减少了CYP3A4/5的抑制作用,药物之间的相互作用最小。III期研究结果表明,nafithromycin对多种呼吸道感染以及细胞内非典型病原体有效,而其他方法很难治疗。没有遇到明显的ae。本文综述了其他抗生素的不良反应,以及nafithromycin相对于其他药物的益处,nafithromycin的发展,作用机制,构效关系,临床疗效,通过各种途径克服抗生素耐药性的给药策略,对抗抗生素耐药性的策略,以及应对全球抗生素耐药性挑战的未来展望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current Microbiology
Current Microbiology 生物-微生物学
CiteScore
4.80
自引率
3.80%
发文量
380
审稿时长
2.5 months
期刊介绍: Current Microbiology is a well-established journal that publishes articles in all aspects of microbial cells and the interactions between the microorganisms, their hosts and the environment. Current Microbiology publishes original research articles, short communications, reviews and letters to the editor, spanning the following areas: physiology, biochemistry, genetics, genomics, biotechnology, ecology, evolution, morphology, taxonomy, diagnostic methods, medical and clinical microbiology and immunology as applied to microorganisms.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信