Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin

J. Nowakowska1, D. R. Cameron¹, A. De Martino², J. Kühn¹, S. Le Fresne-Languille², S. Leuillet², Y. Amouzou²,
F. Wittke³, T. Carton², F. Le Vacon², R. L. Chaves³, V. Nicolas-Metral¹ and G. Vuagniaux¹

¹ Translational Medicine Department, Debiopharm International SA, Chemin Messidor 5-7, 1006 Lausanne, Switzerland
²Research and Development Department, Biofortis SAS, 3 route de la Chatterie, 44800 Saint-Herblain, France
³Clinical Development Department, Debiopharm International SA, Chemin Messidor 5-7, 1006 Lausanne, Switzerland

Journal of Antimicrobial Chemotherapy, available online on June 9th, 2023, dkad181

Background
Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation.

Objectives
To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota.