In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria

Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult and with variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and to explore the cross-resistance with the currently used FQs. A total of 12 pre-extensively drug-resistant (XDR) Mtb, 2 XDR, 36 fully drug susceptible strains and 41 NTM isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimal inhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonary epithelial cells were also determined. DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, no cross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that were already resistant to LX/MOX. DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.

Instituto de Biotecnología

Fil: Imperiale, Belen Rocio. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina

Fil: Imperiale, Belen Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Fil: Mancino, María Belén. Hospital Dr. Antonio A. Cetrángolo. Laboratorio de Referencia del Programa de Control de la Tuberculosis de la provincia de Buenos Aires; Argentina

Fil: Moyano, Roberto Damian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina

Fil: Moyano, Roberto Damian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Fil: de la Barrera, Silvia. Academia Nacional de Medicina. Instituto de Medicina Experimental (IMEX); Argentina

Fil: de la Barrera, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Fil: Morcillo, Nora. Hospital Dr. Antonio A. Cetrángolo. Laboratorio de Referencia del Programa de Control de la Tuberculosis de la provincia de Buenos Aires; Argentina