Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro activity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital Yamuna Devi Bakthavatchalam 1 , Abirami Shankar 1 , Rajeshwari Muniyasamy 1 , John Victor Peter 2 , Zervos Marcus 3 , Hariharan Triplicane Dwarakanathan 4 , Karthik Gunasekaran 5 , Ramya Iyadurai 5 and Balaji Veeraraghavan 1 * 1 Department of Clinical Microbiology, Christian Medical College, Vellore 632004, India; 2 Department of Critical Care Medicine, Christian Medical College, Vellore 632004, India; 3 Division of Infectious Disease, Henry Ford Health System, Detroit, MI 48202, USA; 4 Department of Orthopaedics, Christian Medical College, Vellore 63200, India; 5 Department of Medicine, Unit V, Christian Medical College, Vellore 632004, India *Corresponding author. E-mail: vbalaji@cmcvellore.ac.in Received 16 December 2019; returned 18 February 2020; revised 9 March 2020; accepted 20 March 2020 Objectives: Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoqui- nolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus iso- lates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. Methods: Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013–19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was under- taken to detect the Bengal Bay clone. Results: Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC 50 and MIC 90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. Conclusions: The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections. Introduction In India, MRSA infections continue to be therapeutically challeng- ing both in hospitals and in the community. 1 Vancomycin, teico- planin and linezolid are the standard-of-care antibiotics for nosocomial MRSA infections despite lacking features of a ‘work- horse antibiotic’ such as potent bactericidal action and a favour- able safety profile. High-dose vancomycin is often needed in order to tackle ‘MIC creep’. However, this requires therapeutic drug moni- toring to reduce the risk of nephrotoxicity, especially in renally impaired patients. 2 Although linezolid offers the convenience of oral administration, longer therapy is often associated with myelo- suppression, requiring monitoring of blood parameters. Recent reports suggest overexposure-driven safety concerns with linezolid in patients with renal impairment. 3 Furthermore, owing to the poor bactericidal activity, linezolid is not preferred in immunosup- pressed and bacteraemia patients. Daptomycin, though bacteri- cidal, is ineffective in pneumonia and associated bacteraemia. Thus, patients with hospital-acquired pneumonia, bloodstream infections, bone and joint infections and diabetic foot infections are in need of novel workhorse anti-MRSA therapies with an oral option for switch-over convenience. V C The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com. 2156 J Antimicrob Chemother 2020; 75: 2156–2159 doi:10.1093/jac/dkaa142 Advance Access publication 3 May 2020 Downloaded from https://academic.oup.com/jac/article/75/8/2156/5828350 by guest on 20 August 2022