title: Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics.
abstract: AFN-1252, a potent enoyl-ACP reductase (FabI) inhibitor, is under development for the treatment of Staphylococcus aureus infections. The activity of AFN-1252 against two isolates of S. aureus, MSSA 26213 and MRSA S186, was studied in an in vitro pharmacodynamic  model simulating AFN-1252 pharmacokinetics in man. Reductions in bacterial viable count over the first 6 hours were generally 1-2 logs and maximal reductions in viable count were generally achieved at fAUC/MIC ratios of 100-200. Maximum reductions in viable count against  MSSA 29213 and MRSA S186 were approximately 4 logs, achieved by 450 mg q12h (fAUC/MIC = 1875) dosing at 28 hours. Staphylococcal resistance to AFN-1252 did not develop throughout the 48-hour experiments. As multidrug resistance continues to increase, these studies support  the continued investigation of AFN-1252 as a targeted therapeutic for staphylococcal infections.
authors: Laboratory for Antimicrobial Pharmacodynamics, The New York State Center of Excellence in Bioinformatics, University at Buffalo, State University of New York, NY14203, USA. btsuji@buffalo.edu
authors: Brian T
authors: BT
authors: Tsuji
authors: Yoriko
authors: Y
authors: Harigaya
authors: Alan J
authors: AJ
authors: Lesse
authors: Alan
authors: A
authors: Forrest
authors: Dung
authors: D
authors: Ngo
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011753:Pyrones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: C521531:API 1252; D000900:Anti-Bacterial Agents; D001572:Benzofurans; D011753:Pyrones