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

The Journal of Antibiotics volume 77, pages 306–314 (2024)Cite this article

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Abstract

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.

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Acknowledgements

DC-159a was provided by Daiichi Sankyo Co., Ltd. (Tokyo, Japan). This work was financially supported by National Agency of Scientific and Technological Promotion (PICT 2020-1134).

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Authors and Affiliations

  1. Institute of Experimental Medicine (IMEX)-CONICET, National Academy of Medicine, Buenos Aires City, Argentina

    Belén R. Imperiale & Silvia de la Barrera

  2. Dr. Cetrángolo Hospital, Florida, Buenos Aires Province, Argentina

    María B. Mancino & Nora S. Morcillo

  3. IABIMO-CONICET, INTA CiCVyA, Hurlingham, Buenos Aires Province, Argentina

    Roberto D. Moyano

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Correspondence to Belén R. Imperiale.

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Imperiale, B.R., Mancino, M.B., Moyano, R.D. et al. In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria. J Antibiot 77, 306–314 (2024). https://doi.org/10.1038/s41429-024-00709-3

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