Synergistic interactions of indole-2-carboxamides and β-lactam antibiotics against Mycobacterium abscessus

Clement Raynaud (1) , Wassim Daher (1) , Françoise Roquet-Banères (1) , Matt Johansen (1) , Jozef Stec (2) , Oluseye Onajole (3) , Diane Ordway (4) , Alan Kozikowski (5) , Laurent Kremer (1, 6)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 MBKU - Marshall B. Ketchum University [Fullerton, CA, USA]
3 Roosevelt University [Chicago]
4 CSU - Colorado State University [Fort Collins]
5 Starwise Therapeutics LLC [Chicago]
6 INSERM - Institut National de la Santé et de la Recherche Médicale

New drugs or therapeutic combinations are urgently needed against Mycobacterium abscessus Previously, we demonstrated the potent activity of indole-2-carboxamides 6 and 12 against M. abscessus. We show here that these compounds act synergistically with imipenem and cefoxitin in vitro and increase the bactericidal activity of the β-lactams against M. abscessus In addition, compound 12 also displays synergism with imipenem and cefoxitin within infected macrophages. The clinical potential of these new drug combinations requires further evaluation.

Mots clés: Bëta-lactam; MmpL3; drug 28 synergism; macrophage; therapeutic activity; Mycobacterium abscessus; indole-2-carboxamide

Domaines: Sciences du Vivant [q-bio]; Microbiologie et Parasitologie

Clement Raynaud, Wassim Daher, Françoise Roquet-Banères, Matt Johansen, Jozef Stec, et al.. Synergistic interactions of indole-2-carboxamides and β-lactam antibiotics against Mycobacterium abscessus. Antimicrobial Agents and Chemotherapy, 2020, [Epub ahead of print] (5), pp.AAC.02548-19. ⟨10.1128/AAC.02548-19⟩. ⟨hal-02479144⟩