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.

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Main Authors: Imperiale, Belen Rocio, Mancino, María Belén, Moyano, Roberto Damian, de la Barrera, Silvia, Morcillo, Nora
Format: info:ar-repo/semantics/artículo biblioteca
Language:eng
Published: Japan Antibiotics Research Association 2024-05
Subjects:Antibiotics, Tuberculosis, Mycobacterium, Antimicrobial Resistance, Antibiótico, Resistencia a los Antimicrobianos,
Online Access:http://hdl.handle.net/20.500.12123/18738
https://www.nature.com/articles/s41429-024-00709-3
https://doi.org/10.1038/s41429-024-00709-3
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spelling oai:localhost:20.500.12123-187382024-08-01T10:14:36Z In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria Imperiale, Belen Rocio Mancino, María Belén Moyano, Roberto Damian de la Barrera, Silvia Morcillo, Nora Antibiotics Tuberculosis Mycobacterium Antimicrobial Resistance Antibiótico Resistencia a los Antimicrobianos 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 2024-08-01T10:06:25Z 2024-08-01T10:06:25Z 2024-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/18738 https://www.nature.com/articles/s41429-024-00709-3 1881-1469 https://doi.org/10.1038/s41429-024-00709-3 eng info:eu-repo/semantics/restrictedAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf Japan Antibiotics Research Association The Journal of Antibiotics 77 (5) : 306-314 (May 2024)
institution INTA AR
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country Argentina
countrycode AR
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libraryname Biblioteca Central del INTA Argentina
language eng
topic Antibiotics
Tuberculosis
Mycobacterium
Antimicrobial Resistance
Antibiótico
Resistencia a los Antimicrobianos
Antibiotics
Tuberculosis
Mycobacterium
Antimicrobial Resistance
Antibiótico
Resistencia a los Antimicrobianos
spellingShingle Antibiotics
Tuberculosis
Mycobacterium
Antimicrobial Resistance
Antibiótico
Resistencia a los Antimicrobianos
Antibiotics
Tuberculosis
Mycobacterium
Antimicrobial Resistance
Antibiótico
Resistencia a los Antimicrobianos
Imperiale, Belen Rocio
Mancino, María Belén
Moyano, Roberto Damian
de la Barrera, Silvia
Morcillo, Nora
In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
description 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.
format info:ar-repo/semantics/artículo
topic_facet Antibiotics
Tuberculosis
Mycobacterium
Antimicrobial Resistance
Antibiótico
Resistencia a los Antimicrobianos
author Imperiale, Belen Rocio
Mancino, María Belén
Moyano, Roberto Damian
de la Barrera, Silvia
Morcillo, Nora
author_facet Imperiale, Belen Rocio
Mancino, María Belén
Moyano, Roberto Damian
de la Barrera, Silvia
Morcillo, Nora
author_sort Imperiale, Belen Rocio
title In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
title_short In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
title_full In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
title_fullStr In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
title_full_unstemmed In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria
title_sort in vitro and ex vivo activity of the fluoroquinolone dc-159a against mycobacteria
publisher Japan Antibiotics Research Association
publishDate 2024-05
url http://hdl.handle.net/20.500.12123/18738
https://www.nature.com/articles/s41429-024-00709-3
https://doi.org/10.1038/s41429-024-00709-3
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