Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea

Jnawali, Hum Nath; Hwang, Sung Chul; Park, Young Kil; Kim, Hye-Jin; Lee, Yeong Seon; Chung, Gyung Tae; Choe, Kang Hyeon; Ryoo, Sungweon

doi:10.1016/j.diagmicrobio.2013.02.035

Cited by 67 publications

(53 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the mutation frequencies in CAP-and KAN/AKM-resistant isolates (75.0% and 100.0%) were inconsistent with previous reports (19,(27)(28)(29)(30). One possible reason was that the number of CAP-and KAN/AKM-resistant isolates investigated in our study was very small.…”

Section: Discussioncontrasting

confidence: 55%

“…The mutation frequencies in SM-, EMB-, PZA-, and OFX-resistant isolates were 88.6%, 76.5%, 84.6%, and 77.8%, respectively, which were in agreement with the findings from many investigations (19,(26)(27)(28). However, the mutation frequencies in CAP-and KAN/AKM-resistant isolates (75.0% and 100.0%) were inconsistent with previous reports (19,(27)(28)(29)(30).…”

Section: Discussionsupporting

confidence: 41%

“…The most common mutations among these drug-resistant isolates were katG 315 , inhA15, rpoB 531 , rpoB 526 and rpoB 516 , rpsL 43 , rrs 514 , embB 306 , rrs 1401 , and gyrA 94 and gyrA 90 , as previously reported (19,(27)(28)(29)(30)33). For the pncA gene, although codon 96 was the location of major mutation, it was found in only 3 PZA-resistant isolates (11.5%).…”

Section: Discussionmentioning

confidence: 68%

See 2 more Smart Citations

Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium tuberculosis in Hunan, China

Zhao

Chen

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 55%

Section: Discussionsupporting

confidence: 41%

Section: Discussionmentioning

confidence: 68%

See 1 more Smart Citation

Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium tuberculosis in Hunan, China

Zhao

Chen

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Phenotypic drug susceptibility testing was performed on all 603 isolates by the absolute concentration method on LJ medium to determine the susceptibility to AMK and KAN using a critical concentration of 40 g/ml (the standard concentration used during 2012 when the isolates were tested) for both the antibiotics (27) at the International Tuberculosis Research Center (ITRC), South Korea. MICs of AMK and KAN for 173/603 samples were also evaluated using TREK Sensititre MycoTB MIC plates (MycoTB; TREK Diagnostic Systems, Cleveland, OH, USA) as described previously (28).…”

Section: Methodsmentioning

confidence: 99%

Genotypic Susceptibility Testing of Mycobacterium tuberculosis Isolates for Amikacin and Kanamycin Resistance by Use of a Rapid Sloppy Molecular Beacon-Based Assay Identifies More Cases of Low-Level Drug Resistance than Phenotypic Lowenstein-Jensen Testing

et al. 2015

View full text Add to dashboard Cite

eResistance to amikacin (AMK) and kanamycin (KAN) in clinical Mycobacterium tuberculosis strains is largely determined by specific mutations in the rrs gene and eis gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical M. tuberculosis DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including LowensteinJensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the rrs gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However, eis promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated eis promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the whiB7 5= untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these whiB7 5= UTR mutations in KAN resistance.T uberculosis (TB) was declared a global public emergency nearly 20 years ago (1). Although the rate of new cases of TB has been decreasing worldwide, the millennium developmental goal target of a 50% disease reduction by 2015 is unlikely to be achieved (1). An increase in the incidence of multidrug-resistant (MDR) and extensively drug resistant (XDR) TB is a serious threat to these reduction goals (1). Patients with drug-resistant TB are best identified as rapidly as possible so that appropriate infection control and treatments can be quickly initiated (2).Conventional phenotypic methods can take weeks to months to fully define the drug resistance pattern of Mycobacterium tuberculosis isolates due to the very slow growth of this bacterium (3-5). Molecular tests offer the promise of more rapid drug resistance detection. A number of tests are available to detect resistance to many of the first-line anti-TB drugs (6-8). However, there are fewer rapid tests available to test for resistance to the injectable second-line drugs amikacin (AMK), kanamycin (KAN), and capreomycin (CAP). DNA sequencing studies suggest that most cases of resistance to injectable drugs can be identified by detecting mutations in positions 1401, 1402, and 1484 in the M. tuberculosis 16S rRNA (rrs) gene and between nucleotides Ϫ...

show abstract

“…Prevalence of these mutations among the MDR-TB and XDR-TB isolates were reported in other countries also. [34][35][36][37] We analyzed the demographical background of the patients along with the phylogenetic profile of the isolates and corresponding mutations. Among the 13 patients with second-line drug resistance, 53.8% were immigrants.…”

Section: Discussionmentioning

confidence: 99%

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia

Varghese

Al‐Hajoj

2017

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. In Saudi Arabia, there were no nationwide screening studies conducted so far to determine the aminoglycoside and fluoroquinolone resistance among multidrug-resistant tuberculosis (MDR-TB) isolates. Therefore, as the first attempt in the country, a retrospective analysis has been conducted on a nationwide collection of 2,956 M. tuberculosis clinical isolates screened with phenotypic drug susceptibility testing to define MDR-TB. Enrolled MDR-TB isolates were subjected to second-line drug susceptibility testing, detection of mutations conferring resistance to aminoglycosides and fluoroquinolone, followed by 24-loci mycobacterial interspersed repetitive unitvariable number of tandem repeat typing and spoligotyping. Overall, 83 isolates were identified as MDR-TB, and 13 (15.7%) isolates showed resistance to second-line drugs. Moxifloxacin (low level) showed higher resistant rates (10.8%) followed by ofloxacin (7.2%), capreomycin (3.6%), kanamycin (3.6%), and amikacin (2.4%). Overall fluoroquinolone resistance was 12%, whereas aminoglycoside resistance was 7.2%. Predominant mutations conferring resistance to fluoroquinolone were found in gyrA A90V and D94G, whereas aminoglycoside resistance was observed only with rrs gene A1401G mutation. The corresponding strain lineages predominated with Indo-Oceanic and EastAfrican Indian origin. Interestingly, none of the isolates with second-line drug resistance was defined as extensively drug-resistant TB (XDR-TB). Surprisingly, many isolates (50.6%) were panresistant to first-line drugs. Saudi Arabia faces considerable burden of fluoroquinolone-and aminoglycoside-resistant MDR-TB. Higher incidence of panresistant MDR-TB reveals a threat for the emergence of XDR-TB strains in the near future.

show abstract

Characterization of mutations in multi- and extensive drug resistance among strains of Mycobacterium tuberculosis clinical isolates in Republic of Korea

Cited by 67 publications

References 35 publications

Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium tuberculosis in Hunan, China

Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium tuberculosis in Hunan, China

Genotypic Susceptibility Testing of Mycobacterium tuberculosis Isolates for Amikacin and Kanamycin Resistance by Use of a Rapid Sloppy Molecular Beacon-Based Assay Identifies More Cases of Low-Level Drug Resistance than Phenotypic Lowenstein-Jensen Testing

First Insight Into the Fluoroquinolone and Aminoglycoside Resistance of Multidrug-Resistant Mycobacterium tuberculosis in Saudi Arabia

Contact Info

Product

Resources

About