Afabicin, a first-in-class anti-staphylococcal antibiotic, in the treatment of acute bacterial skin and skin structure infections: clinical non-inferiority to vancomycin/linezolid.

Afabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono, an enoyl-acyl carrier protein reductase (FabI) inhibitor, and is a first-in-class antibiotic with novel mode of action to specifically target fatty acid synthesis in Staphylococcus spp. The efficacy, safety and tolerability of afabicin were compared with vancomycin/linezolid in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) due to staphylococci in this multicenter, parallel group, double-blind and double-dummy phase 2 study. Randomized patients (1:1:1) received either: low dose (LD) afabicin (IV 80 mg, then oral 120 mg, BID); high dose (HD) afabicin (IV 160 mg, then oral 240 mg, BID); or vancomycin/linezolid (IV vancomycin 1 g or 15 mg/kg, then oral linezolid 600 mg, BID). The most frequent baseline pathogen was Staphylococcus aureus (97.5% of microbiological intent-to-treat [mITT] population), and 50.4% of patients had methicillin-resistant S. aureus Clinical response rates at 48-72 h post-randomization in the mITT population were comparable among treatment groups (94.6%, 90.1% and 91.1%, respectively). Both LD and HD afabicin were non-inferior to vancomycin/linezolid (differences: -3.5%, 95% CI [-10.8%, 3.9%] and 1.0%, 95% CI [-7.3%, 9.2%], respectively). Most common treatment-emergent adverse events were mild, and were headache (9.1% and 16.8%) and nausea (6.4% and 8.4%) with LD and HD afabicin, respectively.Afabicin was efficacious and well-tolerated in the treatment of ABSSSI due to staphylococci, and these data support further development of afabicin for the treatment of ABSSSI and potentially other types of staphylococcal infections.