Second-line drug susceptibilities of multidrug-resistant tuberculosis strains isolated in Thailand: an update

Chaiprasert, Angkana; Srimuang, S; Tingtoy, Nipa; Makhao, Nampueng; Sirirudeeporn, Parach; Tomnongdee, N; Theankeaw, Orathai; Charoensook, S; Leechawengwongs, Manoon; Prammananan, Therdsak

doi:10.5588/ijtld.13.0197

Cited by 7 publications

(5 citation statements)

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“…Five of the six second-line drugs did not present a significant decline between 2008 and 2013. Resistance to OFX among MDR-TB patients ranked second in 2008 (28.9%) and first in 2013 (27.7%), with figures higher than those of the Chinese national average (25.4%), Thailand (15.0%), South Africa (4.8%) and India (9.0%) [ 2 , 20 – 22 ]. OFX is a broad-spectrum antibiotic which is usually used in clinical treatment for many other infections [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999–2013

Zhang

Liu

et al. 2017

Global Health Action

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Background: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) hinder the progress of TB control.Objective: To track the trend of drug-resistant tuberculosis (DR-TB) prevalence in Zhejiang Province from 1999 to 2013, and identify risk factors of resistance to second-line drugs among MDR-TB patients.Design: Four DR-TB surveys had been done in Zhejiang Province in 1999, 2004, 2008 and 2013 through questionnaires, in which demographic and epidemiological items were included. After questionnaires, drug susceptibility testing (DST) targeted at four first-line drugs was done for all TB patients and DST targeted at six second-line drugs (only in 2008 and 2013) for MDR-TB patients. The drug resistance trend over time was analyzed using the Cochran–Armitage test. The factors associated with resistance to second-line drugs among MDR-TB patients were examined by a multivariate logistic regression model.Results: Of 936 patients enrolled, 27 (3.21%) and 20 (21.28%) MDR-TB cases were registered as new and previously treated cases, respectively. MDR-TB showed a decreasing trend (Z = −3.31, p < 0.01) while resistance to any first-line drugs showed an increasing trend (Z = 5.22, p < 0.001), from 1999 to 2013. The highest resistance rate was shown to ofloxacin among MDR-TB patients both in 2008 (28.8%) and in 2013 (27.7%), while resistance to para-aminosalicylate decreased significantly (Z = −2.06, p = 0.04) between 2008 and 2013. MDR-TB patients aged 45–65 years (OR = 5.00, p = 0.02) were more likely to be resistant to any second-line drugs.Conclusions: DR-TB including MDR-TB remains a major public health problem in Zhejiang Province. Further efforts on MDR-TB control should be conducted to hinder drug resistance, including critical clinical use of anti-TB antibiotics and preventing transmission.

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Section: Discussionmentioning

confidence: 99%

Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999–2013

Zhang

Liu

et al. 2017

Global Health Action

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“…The emergence of drug-resistant TB, including MDR-TB, QR-TB and XDR-TB, is continuously reported in Thailand (Chaiprasert et al, 2014;World Health Organization, 2014). Elucidation of the mechanisms underlying this problem is required for the development of appropriate control strategies.…”

Section: Discussionmentioning

confidence: 99%

“…We analyzed data from routine second-line drug susceptibility testing of MDR-TB between 2003 and 2011. During this eight years period, quinolone-resistant tuberculosis (QR-TB), which is one form of pre-XDR-TB, increased from 9% to 15% of MDR-TB isolates, while XDR-TB isolates, which are resistant to quinolone and a second-line injectable drug, comprised 4% of MDR-TB isolates (Chaiprasert et al, 2014). Elucidation of the factors driving the emergence of drug-resistant TB is required to optimize strategies for TB control.…”

Section: Introductionmentioning

confidence: 99%

Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant Mycobacterium tuberculosis isolates in Thailand

Disratthakit

Meada

Prammananan

et al. 2015

Infection, Genetics and Evolution

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Drug-resistant tuberculosis (TB), which includes multidrug-resistant (MDR-TB), quinolone-resistant (QR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is a serious threat to TB control. We aimed to characterize the genotypic diversity of drug-resistant TB clinical isolates collected in Thailand to establish whether the emergence of drug-resistant TB is attributable to transmitted resistance or acquired resistance. We constructed the first molecular phylogeny of MDR-TB (n=95), QR-TB (n=69) and XDR-TB (n=28) in Thailand based on spoligotyping and proposed 24-locus multilocus variable-number of tandem repeat analysis (MLVA). Clustering analysis was performed using the unweighted pair group method with arithmetic mean. Spoligotyping identified the Beijing strain (SIT1) as the most predominant genotype (n=139; 72.4%). The discriminatory power of 0.9235 Hunter-Gaston Discriminatory Index (HGDI) with the 15-locus variable-number tandem repeats of mycobacterial interspersed repetitive units typing was improved to a 0.9574 HGDI with proposed 24-locus MLVA, thereby resulting in the subdivision of a large cluster of Beijing strains (SIT1) into 17 subclusters. We identified the spread of drug-resistant TB clones caused by three different MLVA types in the Beijing strain (SIT1) and a specific clone of XDR-TB caused by a rare genotype, the Manu-ancestor strain (SIT523). Overall, 49.5% of all isolates were clustered. These findings suggest that a remarkable transmission of drug-resistant TB occurred in Thailand. The remaining 50% of drug-resistant TB isolates were unique genotypes, which may have arisen from the individual acquisition of drug resistance. Our results suggest that transmitted and acquired resistance have played an equal role in the emergence of drug-resistant TB. Further characterization of whole genome sequences of clonal strains could help to elucidate the mycobacterial genetic factors relevant for drug resistance, transmissibility and virulence.

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“…Resistance to quinolones can pave the way for the emergence of XDR-TB. In Thailand, the quinolone resistance rates among MDR-TB cases increased from 9% in 2005 to 15% in 2011 (10,11). Early detection of quinolone-resistant tuberculosis will help in choosing the proper regimen for the treatment of MDR-TB and in preventing the development of XDR-TB.…”

mentioning

confidence: 99%

Role of gyrB Mutations in Pre-extensively and Extensively Drug-Resistant Tuberculosis in Thai Clinical Isolates

Disratthakit

Prammananan

Tribuddharat

et al. 2016

Antimicrob Agents Chemother

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DNA gyrase mutations are a major cause of quinolone resistance in Mycobacterium tuberculosis. We therefore conducted the first comprehensive study to determine the diversity of gyrase mutations in pre-extensively drug-resistant (pre-XDR) (n ‫؍‬ 71) and extensively drug-resistant (XDR) (n ‫؍‬ 30) Thai clinical tuberculosis (TB) isolates. All pre-XDR-TB and XDR-TB isolates carried at least one mutation within the quinolone resistance-determining region of GyrA ( . MIC and DNA gyrase supercoiling inhibition assays were performed to determine the role of gyrase mutations in quinolone resistance. Compared to the MICs against M. tuberculosis H37Rv, the levels of resistance to all quinolones tested in the isolates that carried GyrA-D94G or GyrB-N538D (8-to 32-fold increase) were significantly higher than those in isolates bearing GyrA-D94A or GyrA-A90V (2-to 8-fold increase) (P < 0.01). Intriguingly, GyrB-E540D led to a dramatic resistance to later-generation quinolones, including moxifloxacin, gatifloxacin, and sparfloxacin (8-to 16-fold increases in MICs and 8.3-to 11.2-fold increases in 50% inhibitory concentrations [IC 50 s]). However, GyrB-E540D caused low-level resistance to early-generation quinolones, including ofloxacin, levofloxacin, and ciprofloxacin (2-to 4-fold increases in MICs and 1.5-to 2.0-fold increases in IC 50 s). In the present study, DC159a was the most active antituberculosis agent and was little affected by the gyrase mutations described above. Our findings suggest that although they are rare, gyrB mutations have a notable role in quinolone resistance, which may provide clues to the molecular basis of estimating quinolone resistance levels for drug and dose selection.

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Second-line drug susceptibilities of multidrug-resistant tuberculosis strains isolated in Thailand: an update

Cited by 7 publications

References 1 publication

Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999–2013

Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999–2013

Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant Mycobacterium tuberculosis isolates in Thailand

Role of gyrB Mutations in Pre-extensively and Extensively Drug-Resistant Tuberculosis in Thai Clinical Isolates

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