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

IMPERIALE, BELÉN R.; MANCINO, MARÍA B.; MOYANO, ROBERTO D.; DE LA BARRERA, SILVIA; MORCILLO, NORA S.

JOURNAL OF ANTIBIOTICS

JAPAN ANTIBIOTICS RESEARCH ASSOC

Año: 2024

0021-8820

Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistanttuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and theemergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult andwith variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and toexplore 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 isolateswere included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimalinhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonaryepithelial cells were also determined.DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, nocross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that werealready resistant to LX/MOX.DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.