Afabicin is an antibiotic targeting Staphylococcus aureus, exhibiting highly effective inhibitory activity against both susceptible and methicillin-resistant (MRSA) S. aureus strains. It is used to treat acute bacterial skin and skin structure infections. Afabicin is the prodrug of Debio1452.

Afabicin (Debio1450) is the prodrug of Debio1452, which specifically targets staphylococci with minimal activity against other bacteria. Debio1452 acts by inhibiting the fatty acid synthesis enzyme FabI and shows potent activity against Staphylococcus aureus, with MIC₅₀ and MIC₉₀ values of 0.004 and 0.008 μg/mL, respectively.

Methods:
To evaluate the in vivo antibacterial activity of Afabicin against Staphylococcus aureus, including MRSA, particularly under immunosuppressed conditions, a neutropenic mouse thigh infection model was established. Female ICR or Swiss Webster mice were rendered immunosuppressed by cyclophosphamide treatment, followed by intramuscular injection of 9 S. aureus strains into the left thigh. Afabicin treatment began 2 hours post-infection via intravenous or intraperitoneal injection, using either a single dose of 129 mg/kg or repeated doses every 6 hours (ranging from 0.011 to 190 mg/kg). Thigh tissues were collected at multiple time points for bacterial colony counting to assess efficacy.
Results:
Afabicin significantly reduced bacterial burden at the infection site and demonstrated potent in vivo activity against S. aureus, including MRSA, with MIC values ranging from 0.004 to 0.06 mg/L. [2]