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Войти в исследования Frontiers in cellular and infection microbiology · 2026
Alarming levels of fluoroquinolone resistance among MDR-TB patients in Poland: molecular and phenotypic analysis.
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Kozińska Monika, Głogowska Agnieszka, Minias Alina, Dziadek Jarosław, Augustynowicz-Kopeć Ewa
Аннотация
BACKGROUND: Fluoroquinolones (FQs) are a cornerstone of modern multidrug-resistant tuberculosis (MDR-TB) treatment, particularly within the WHO-recommended all-oral BPaLM regimen. The emergence of FQ-resistant Mycobacterium tuberculosis (MTB) poses a critical threat to these life-saving therapies. While the global proportion of FQ resistance among MDR/RR-TB cases is estimated at 19%, phenotypic and molecular data from low-incidence countries in Central and Eastern Europe remain limited. This study aimed to comprehensively assess the FQ resistance profile of MDR/RR-TB strains isolated in Poland between 2022 and 2024.
METHODS: We analyzed 240 drug-resistant MTB isolates (228 MDR and 12 rifampicin-resistant) collected nationwide. Phenotypic drug susceptibility testing (DST) was performed using the Bactec MGIT 960 system. Isolates demonstrating resistance to levofloxacin and/or moxifloxacin (n = 104) were further analyzed using Deeplex-Myc TB targeted next-generation sequencing (tNGS) to identify mutations within the quinolone resistance-determining region (QRDR) and determine strain spoligotypes.
RESULTS: Phenotypic FQ resistance was detected in an alarming 43.0% (104/240) of isolates. Mutational analysis revealed eight variants in the gyrA gene and two variants in the gyrB gene. The most frequent mutations were D94G (44.2%), D94N (18.3%), and D94A (12.5%). Genome sequencing allowed the identification of 11 molecular families (spoligotypes), with the Beijing genotype being by far the dominant one and accounting for 91.0% of all isolates.
CONCLUSIONS: Our findings demonstrate a substantial and concerning burden of FQ resistance among MDR-TB strains in Poland, significantly exceeding global averages. The high prevalence of QRDR mutations and the dominance of the Beijing genotype highlight the urgent need for systematic molecular surveillance and rapid NGS-based diagnostics. Such measures are essential to ensure the effectiveness of the BPaLM regimen and prevent the further spread of highly drug-resistant TB.
METHODS: We analyzed 240 drug-resistant MTB isolates (228 MDR and 12 rifampicin-resistant) collected nationwide. Phenotypic drug susceptibility testing (DST) was performed using the Bactec MGIT 960 system. Isolates demonstrating resistance to levofloxacin and/or moxifloxacin (n = 104) were further analyzed using Deeplex-Myc TB targeted next-generation sequencing (tNGS) to identify mutations within the quinolone resistance-determining region (QRDR) and determine strain spoligotypes.
RESULTS: Phenotypic FQ resistance was detected in an alarming 43.0% (104/240) of isolates. Mutational analysis revealed eight variants in the gyrA gene and two variants in the gyrB gene. The most frequent mutations were D94G (44.2%), D94N (18.3%), and D94A (12.5%). Genome sequencing allowed the identification of 11 molecular families (spoligotypes), with the Beijing genotype being by far the dominant one and accounting for 91.0% of all isolates.
CONCLUSIONS: Our findings demonstrate a substantial and concerning burden of FQ resistance among MDR-TB strains in Poland, significantly exceeding global averages. The high prevalence of QRDR mutations and the dominance of the Beijing genotype highlight the urgent need for systematic molecular surveillance and rapid NGS-based diagnostics. Such measures are essential to ensure the effectiveness of the BPaLM regimen and prevent the further spread of highly drug-resistant TB.