Abstract
Accurate and timely detection of drug resistance can minimize the risk of further resistance development and lead to effective treatment. The aim of this study was to determine the resistance to first/second-line anti-tuberculosis drugs in rifampicin/multidrug-resistant Mycobacterium tuberculosis (RR/MDR-MTB) isolates. Molecular epidemiology of strains was determined using whole genome sequencing (WGS)-based genotyping. A total of 35 RR/MDR-MTB isolates were subjected to drug susceptibility testing against first/second-line drugs using 7H9 Middlebrook in broth microdilution method. Illumina technology was used for paired-end WGS applying a Maxwell 16 Cell DNA Purification kit and the NextSeq platform. Data analysis and single nucleotide polymorphism calling were performed using MTBseq pipeline. The genome-based resistance to each drug among the resistant phenotypes was as follows: rifampicin (97.1%), isoniazid (96.6%), ethambutol (100%), levofloxacin (83.3%), moxifloxacin (83.3%), amikacin (100%), kanamycin (100%), capreomycin (100%), prothionamide (100%), D-cycloserine (11.1%), clofazimine (20%), bedaquiline (0.0%), and delamanid (44.4%). There was no linezolid-resistant phenotype, and a bedaquiline-resistant strain was wild type for related genes. The Beijing, Euro-American, and Delhi-CAS were the most populated lineage/sublineages. Drug resistance-associated mutations were mostly linked to minimum inhibitory concentration results. However, the role of well-known drug-resistant genes for D-cycloserine, clofazimine, bedaquiline, and delamanid was found to be more controversial.
Highlights
Multidrug-resistant tuberculosis (MDR-TB), with a wide range of prevalence around the world is considered as a global public health concern [1]
M. tuberculosis was identified by biochemical tests after positive primary culture on Lowenstein Jensen (LJ) medium [13]
Based on the minimum inhibitory concentrations (MICs) results, 35 out of 37 examined strains were confirmed as rifampicin-resistant, and the remaining two isolates, which were susceptible to RIF, were excluded from further analysis
Summary
Multidrug-resistant tuberculosis (MDR-TB), with a wide range of prevalence around the world is considered as a global public health concern [1]. In 2017, approximately 558,000 (483,000–639,000) rifampicin-resistant tuberculosis (RR-TB) cases were estimated, of which 82% were MDR. 3.5% of new cases and 18% of previously treated cases were RR/MDR-TB and reported to be 1.3% and 8.3%, respectively, in Iran [2]. Drug resistance in the neighboring countries of Iran is remarkably higher, as in Afghanistan, Armenia, and Azerbaijan, MDR incidence was 4.1%, 11%, and 13% among new cases, and it was 16%, 47%, and 39% among previously treated patients, respectively [2]. Treatment of patients with MDR-TB is more time-consuming and requires expensive drugs with more toxicity, compared to drug-susceptible TB. Accurate drug susceptibility testing (DST) is required to achieve effective treatment and minimize the risk of further resistance development [4]
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