Producción CyT
Libro de Resumenes del Keystone Symposia. Tuberculosis: Heterogeneity from Experimental Models to Human Disease (B1) - In-Vitro and Ex-vivo Activity of the Fluoroquinolone DC-159a during Mycobacterial Infection
Congreso
Fecha:
2025Editorial y Lugar de Edición:
Keystone Symposia 2025Resumen *
Antimicrobial resistance is a worldwide health problem and it could become the leading cause of death. In 2023, World Health Organization (WHO) estimated the number of incident cases of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) in 400 000. Besides, the emergence of fluoroquinolone resistant (FQ-R) M. tuberculosis (Mtb) is also a global concern, making MDR/RR-TB, pre-XDR-TB (MDR/RR-TB plus FQ-R) and XDR-TB (MDR-TB plus FQ, bedaquiline and/or linezolid-R) treatments difficult and with variable outcome. Moreover, mycobacterioses caused by non-tuberculous mycobacteria (NTM) are highly resistant to several drugs, including FQs. The worldwide incidence and prevalence of mycobacterioses remain unknown. NTM treatment is not well standardized and it has also variable outcomes.Therefore, it is necessary to find alternative drugs with bactericidal effect to treat MDR/pre-XDR/XDR-TB as well as mycobacterioses cases.DC-159a is a broad-spectrum 8-methoxy FQ with a potent antimicrobial activity against several mycobacteria including those FQ-R isolates carrying gyrA gene mutations. Therefore, 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-XDR, 2 XDR, 36 fully drug susceptible Mtb strains and 41 M. avium (MAC) isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), through the minimal inhibitory and bactericidal concentration (MIC and MBC). The DC-159a activity, inside the human macrophages and in the alveolar epithelial cells was also determined.Results showed that 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, pre-XDR, XDR-TB and in mycobacterioses cases. Información suministrada por el agente en SIGEVAPalabras Clave
Drogo-resistenciaDC-159aFluoroquinolonasMicobacterias