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Evolution of resistance to new drugs in high tuberculosis burden country.

N Ciobanu(1,2) A Codreanu(1) N Turcan(1) E Noroc(1,2) D Chesov(1,2) D Rusu(1,2) A Donica(1) V Crudu(1,2)

1:Institute of Phthisiopneumology, Chisinau, Moldova; 2:State University of Medicine and Pharmacy, Chisinau, Moldova

Background: Drug resistance remains a significant challenge in TB treatment and control programs. New agents have shown promising results for MDR/XDR-TB patients, improving the culture conversion rate, reducing mortality. However, in recent years, an increasing number of cases with acquired resistance to new anti-tb drugs have been reported.

Aim: to assess the emergence of resistance to the new antituberculosis drugs: bedaquiline, clofazimine, delamanid and linezolid.

Method: A total of 1037 MDR-TB patients who underwent treatment between January - December 2020 in 3 TB hospitals from Moldova were examined. M.tuberculosis isolates were tested for resistance to fluoroquinolone, bedaquiline, clofazimine, delamanid and linezolid by phenotypic (BACTEC MGIT 960) and molecular (Hain) methods.

Results: Among the 534 new TB cases and 503 previously treated cases, correspondingly 79.1% (n=422) and 60.4 (n=304), were susceptible. Pre-XDR TB was detected in 11.6% (n=62) new cases and 24.5%% (n=123) previously treated cases. XDR TB was present in only 2 patients among new cases and 7.5% % (n=38) previous cases. Any BDQ resistance – 0.4% new cases and 5.7% previously treated cases, any LZ resistance – 4.2% previously treated cases, any CLF resistance –1.9% previously treated cases, any DLM resistance – 0.9% new cases and 3.8% previously treated cases.

Conclusions: The emergence of BQ&DLM resistance is alarming as it may lead to the rapid loss of these new drugs. The development of molecular assays for systematic surveillance of new anti-TB compounds is urgently needed to monitor the emergence of resistance and should be a higher priority when new drugs are introduced.

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