In Vivo Pharmacokinetic/Pharmacodynamic Targets of Levonadifloxacin against Staphylococcus aureus in a Neutropenic Murine Lung Infection Model

  • Antimicrob Agents Chemother. 2019 Jul 25;63(8):e00909-19. doi: 10.1128/AAC.00909-19.
Sachin S Bhagwat  1 ,  Hariharan Periasamy  2 ,  Swapna S Takalkar  2 ,  Rajesh Chavan  2 ,  Pavan Tayde  2 ,  Amol Kulkarni  2 ,  Jaikumar Satav  2 ,  Vineet Zope  2 ,  Mahesh Patel  2
Affiliations
  • 1. Wockhardt Research Centre, Aurangabad, India [email protected].
  • 2. Wockhardt Research Centre, Aurangabad, India.
PMID: 31208999 DOI: 10.1128/AAC.00909-19
Abstract

Levonadifloxacin is a novel benzoquinolizine subclass of fluoroquinolone, active against quinolone-resistant Staphylococcus aureus A phase 3 trial for levonadifloxacin and its oral prodrug was recently completed. The present study identified area under the concentration-time curve for the free, unbound fraction of a drug divided by the MIC (fAUC/MIC) as an efficacy determinant for levonadifloxacin in a neutropenic murine lung Infection model. Mean plasma fAUC/MIC requirement for static and 1 log10 kill effects against 9 S. aureus were 8.1 ± 6.0 and 25.8 ± 12.3, respectively. These targets were employed in the selection of phase 3 doses.

Keywords
ABSSSIs; MRSA; levonadifloxacin.
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