Assessment of In vitro activity of Levonadifloxacin against clinical bacterial isolates in patients admitted in ICU in a tertiary care hospital

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Abstract

Background: Levonadifloxacin, a benzoquinolizine subclass of fluoroquinolones, has demonstrated potent activity against methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant S. aureus (QRSA), vancomycin-intermediate and vancomycin-resistant S. aureus . Its mechanism—preferential inhibition of DNA gyrase with high affinity for topoisomerase IV—enhances its efficacy against resistant Gram-positive bacteria. Despite its approval in India for treating skin and soft tissue infections, data on its activity against Gram-negative organisms remains limited. This study aimed to assess the in vitro activity of levonadifloxacin against clinical bacterial isolates from ICU patients using broth microdilution. Material and Method: This descriptive study was conducted at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, between March 27 and May 25, 2025. A total of 135 non-duplicate clinical isolates from ICU patients (blood, pus, urine, catheter tips, and sterile fluids) were analysed. Isolates were identified via Gram stain, biochemical tests, and MALDI-TOF MS. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Minimum inhibitory concentrations (MICs) for levonadifloxacin were determined using the broth microdilution method as per CLSI 2025 guidelines, with interpretation based on proposed pharmacokinetic/pharmacodynamic breakpoints (≤ 4 µg/ml). Result: Among 135 isolates, 85 (62.96%) were Gram-negative bacilli and 50 (37.04%) were Gram-positive cocci. The most frequent isolates were K. pneumoniae (21.28%), E. coli (17.77%), CONS (17.77%), and P. aeruginosa (15.55%). Methicillin resistance was observed in 47% of S. aureus and 79.16% of CONS. A total of 76.29% of isolates were resistant to levofloxacin; however, all Gram-positive isolates (including MRSA, MRCONS, and vancomycin resistant E. faecalis ) were susceptible to levonadifloxacin. Among Gram-negative bacilli, levonadifloxacin showed limited efficacy and was active only against strains that were already susceptible to levofloxacin. Conclusion: Levonadifloxacin exhibited excellent in vitro activity against Gram-positive cocci, including multidrug-resistant MRSA and VRE, supporting its role in treating ICU-acquired infections. Its oral and IV availability and lack of renal/hepatic dose adjustments make it a valuable therapeutic option. However, its limited efficacy against Gram-negative bacilli highlights the need for further studies and resistance mechanism evaluation.

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