Activity of novel lactone ketolide nafithromycin against multicentric invasive and non-invasive pneumococcal isolates collected in India

Author:

Veeraraghavan Balaji1,Varghese Rosemol1,Saigal Karnika2,Balasubramanian S3,Bai P Sulochana Putli4,Lal Y Binesh1,Neeravi Ayyanraj1,Baskar Pavithra1,Anandhan Kavipriya1,Kumar C P Girish4,Jayaraman Yuvraj4,Nag Vijaya Lakshmi5,Baveja Sujata6,J Bhavana7,Joshi Shrikrishna A8,Iyer Ranganathan9

Affiliation:

1. Christian Medical College, Vellore, Tamil Nadu, India

2. Chacha Nehru Bal Chikitsalaya, New Delhi, India

3. Kanchi Kamakoti Children’s Trust Hospital, Chennai, Tamil Nadu, India

4. ICMR-National Institute of Epidemiology, Chennai, Tamil Nadu, India

5. All India Institute of Medical Science, Jodhpur, Rajasthan, India

6. Lokmanya Tilak Municipal Medical College and Hospital, Sion, Mumbai, India

7. Indira Gandhi Institute of Child Health, Bengaluru, India

8. Central Clinical Microbiology Laboratory, Navi, Mumbai, India

9. Global Hospitals, Hyderabad, India

Abstract

Abstract Background India is among the nations reporting substantial healthcare burden linked to pneumococcal infections. Nafithromycin is a novel lactone ketolide antibiotic, which recently entered Phase 3 development in India for the indication of community-acquired bacterial pneumonia (CABP). Objectives To assess the in vitro activity of nafithromycin against serotyped invasive and non-invasive Streptococcus pneumoniae isolates, collected from nine medical centres across India. Methods A total of 534 isolates of S. pneumoniae were collected during 2015–20 and serotyped as per CDC protocol. A subset of erythromycin-non-susceptible S. pneumoniae (n = 200) was screened for the presence of erm(B) and mef(A/E) genes. A subset of MDR isolates (n = 54) were also subjected to MLST. The MICs of antibiotics were determined by the reference agar-dilution method (CLSI). Susceptibilities of the comparators were interpreted as per CLSI criteria. Results Fifty-nine distinct serotypes were identified among the 534 isolates. Among erythromycin-non-susceptible isolates, erm(B) and mef(A/E) genes were found in 49% and 59% strains respectively, while MLST showed clonal diversity. Azithromycin (67.6% non-susceptible) and clindamycin (31.8% non-susceptible) showed limited activity. Penicillin (for non-meningitis) or quinolone non-susceptibility was low (<11% and <6%, respectively). Nafithromycin showed potent activity with MIC50 and MIC90 of 0.015–0.03 and 0.06 mg/L, respectively, regardless of the macrolide resistance mechanisms. Conclusions Indian pneumococcal isolates show poor susceptibilities to macrolides, in concordance with the global trend. Nafithromycin overcomes erm as well as mef-mediated macrolide resistance mechanisms expressed individually or concurrently in S. pneumoniae. This study supports continued clinical development of nafithromycin for pneumococcal infections including CABP.

Funder

Wockhardt Ltd

Publisher

Oxford University Press (OUP)

Subject

General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3