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New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant Mycobacterium tuberculosis .
- Source :
-
Journal of medical microbiology [J Med Microbiol] 2024 Jul; Vol. 73 (7). - Publication Year :
- 2024
-
Abstract
- Introduction. Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ. Hypothesis. Sfx is more active against drug-resistant Mycobacterium tuberculosis (Mtb) isolates. Aim. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb. Methods. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes. Results. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC <subscript>50</subscript> of 0.0313 µg ml <superscript>-1</superscript> and MIC <subscript>90</subscript> of 0.125 µg ml <superscript>-1</superscript> , which was lower than that of Mfx (MIC <subscript>50</subscript> = 0.0625 µg ml <superscript>-1</superscript> , MIC <subscript>90</subscript> = 1 µg ml <superscript>-1</superscript> ) and Lfx (MIC <subscript>50</subscript> = 0.125 µg ml <superscript>-1</superscript> , MIC <subscript>90</subscript> = 2 µg ml <superscript>-1</superscript> ). We determined the tentative epidemiological cut-off values as 0.5 µg ml <superscript>-1</superscript> for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in gyrA or gyrB , 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident. Conclusion. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.
- Subjects :
- Humans
Whole Genome Sequencing
Fluoroquinolones pharmacology
Mycobacterium tuberculosis drug effects
Mycobacterium tuberculosis genetics
Moxifloxacin pharmacology
Levofloxacin pharmacology
Microbial Sensitivity Tests
Tuberculosis, Multidrug-Resistant microbiology
Tuberculosis, Multidrug-Resistant drug therapy
Drug Resistance, Multiple, Bacterial
Antitubercular Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5644
- Volume :
- 73
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of medical microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 39028256
- Full Text :
- https://doi.org/10.1099/jmm.0.001825