High rates of acquired resistance to fluoroquinolones, bedaquiline and linezolid in patients failing treatment against drug-resistant tuberculosis in the Republic of Moldova.
Dumitru Chesov, Maja Reimann, Tishya Mukherjee, Krishan Tewatia, Olha Konstantynovska, Aliona David, Doina Rusu, Nelly Ciobanu, Valeriu Crudu, Christoph Lange
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引用次数: 0
Abstract
Objectives: Mycobacterium tuberculosis with rifampicin resistance rank among the four critical antimicrobial-resistant pathogens needing priority attention as identified by the World Health Organization (WHO) in 2024. Our objective was to identify causes of treatment failure in patients diagnosed with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) in a nation-wide cohort in the Republic of Moldova, a WHO high-burden country of MDR/RR-TB.
Methods: A retrospective cohort study analyzed national tuberculosis surveillance data (2021-2022) on patients diagnosed with MDR/RR-TB with available baseline and follow-up drug susceptibility testing for WHO Group A drugs. Treatment failure was defined as the absence of sputum culture conversion after six months. Logistic regression was used to identify risk factors associated with treatment failure.
Results: Of 1034 patients initiating MDR/RR-TB treatment, 55 (5.3%) experienced treatment, failure, while 693 (67.1%) were successfully treated. Baseline resistance to WHO Group A drugs was significantly higher in patients with treatment failure than in those with successful outcomes: fluoroquinolones ((32/48 (66.7%) vs. 86/471 (18.3%), p<0.0001), bedaquiline (6/42 (12.5%) vs. 3/468 (0.6%), p<0.0001), and linezolid (12/48 (25.0%) vs. 3/468 (0.6%), p<0.0001). Acquired resistance occurred in 19/48 (39.6%) of those failing treatment but none with successful outcomes, particularly to bedaquiline 13/42 (30.9%), linezolid 6/36 (16.7%), and fluoroquinolones 4/16 (25.0%). Baseline fluoroquinolone resistance (OR 4.7, 95% CI 2.0 - 11.2) and acquired resistance to any WHO Group A drug (OR 63.5, 95% CI 7.7 - 8311.7) were associated with treatment failure.
Conclusions: While frequencies of treatment failure in MDR/RR-TB are low on bedaquiline-containing treatment regimens, we find alarmingly high rates of baseline and acquired drug resistance to key second-line anti-TB drugs as a driver for treatment failure in MDR/RR-TB. Strengthening resistance monitoring, improving adherence, and optimizing individualized regimens are urgently needed to prevent the emergence of extensively drug-resistant (XDR)-TB in high-burden settings of MDR/RR-TB.
期刊介绍：
Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.
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