Activity of novel lactone ketolide nafithromycin against multicentric invasive and non-invasive pneumococcal isolates collected in India. Issue 2 (1st June 2021)

• Record Type: Journal Article
• Authors: Veeraraghavan, Balaji; Varghese, Rosemol; Saigal, Karnika; Balasubramanian, S; Bai, P Sulochana Putli; Lal Y, Binesh; Neeravi, Ayyanraj; Baskar, Pavithra; Anandhan, Kavipriya; Kumar, C P Girish; Jayaraman, Yuvraj; Nag, Vijaya Lakshmi; Baveja, Sujata; J, Bhavana; Joshi, Shrikrishna A; Iyer, Ranganathan
• Is Part Of: JAC-antimicrobial resistance. Volume 3:Issue 2(2021)
• Publication Date: 2021-06-01
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; Drug resistance in microorganisms -- Periodicals; 616.9041
• DOI: 10.1093/jacamr/dlab066
• Languages: English
• ISSNs: 2632-1823

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.