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

Abstract

Objectives Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine 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 isolates 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 undertaken 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 MIC50 and MIC90 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.

Efficacy and safety of intravenous and/or oral levonadifloxacin in the management of secondary bacterial pulmonary infections in COVID-19 patients: findings of a retrospective, real-world, multi-center study

“…The observation in the present study is in agreement with these published findings. 7,[17][18][19][20][21] In this study, the clinical success rate of levonadifloxacin was >90% irrespective of IV or oral regimen, which was comparable to pivotal phase 3 trial in which levonadifloxacin IV and oral regimens demonstrated 91% and 95.2% clinical cure rates. Furthermore, no AEs were encountered for the evaluated 154 patients.…”

“…16 It should be noted that, levonadifloxacin is the lone available oral option with comprehensive coverage (>90% susceptibility) of gram-positive pathogens including MRSA; bestowed with safety features enabling longer duration of therapy. 21,22 With respect to comorbidities, apart from SIRS, patients under assessment were reported to have several complications which included sepsis. In such scenarios, a potent bactericidal antibiotic such as levonadifloxacin could be an ideal choice as compared to a slowly cidal or bacteriostatic antibiotic agent.…”

Structural Characterization of the Millennial Antibacterial (Fluoro)Quinolones—Shaping the Fifth Generation

“…Levonadifloxacin ((12 S )-7-fluoro-8-(4-hydroxypiperidin-1-yl)-12-methyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid) is the active S (−) isomer of nadifloxacin recently approved in India ( Figure 9 ) [ 194 , 195 ]. The S (−) isomer of nadifloxacin, has been shown to be more potent than the R (+) isomer and twice as active as the racemic form of nadifloxacin against Gram-positive and Gram-negative bacteria.…”

Levonadifloxacin

“…As a result, there is a significant increase in the potency of LND in acidic environments. [7][8][9] This feature could be beneficial for intracellular activity and antibacterial action in infections with an acidic environment.…”

“…LND is S-(-)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1yl)-5-methyl-1-oxo-1H,5H-benzo; quinolizine-2-carboxylic acid L-arginine salt tetrahydrate is the active S(-) isomer of nadifloxacin recently approved in India. [8] LND exhibits potent in vitro activity against contemporary S. aureus isolates and Bengal Bay Clone, isolates collected from a large Indian tertiary care hospital. [9] The S(-) isomer of nadifloxacin has been shown to be more potent than the R(+) isomer and twice as active as the racemic form of nadifloxacin against Gram-positive and Gram-negative bacteria.…”