Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics

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.