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Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

ABSTRACT: Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.

SUBMITTER: Kurbatova EV

PROVIDER: S-EPMC4451908 | biostudies-other | 2015 Jun

REPOSITORIES: biostudies-other

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Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

Kurbatova Ekaterina V EV Dalton Tracy T Ershova Julia J Tupasi Thelma T Caoili Janice Campos JC Van Der Walt Martie M Kvasnovsky Charlotte C Yagui Martin M Bayona Jaime J Contreras Carmen C Leimane Vaira V Via Laura E LE Kim HeeJin H Akksilp Somsak S Kazennyy Boris Y BY Volchenkov Grigory V GV Jou Ruwen R Kliiman Kai K Demikhova Olga V OV Cegielski J Peter JP

Emerging infectious diseases 20150601 6

Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line inj ...[more]

PMID: 25988299

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Project description:ObjectiveTo determine the extent of drug resistance in multidrug-resistant tuberculosis (MDR-TB) cases, we conducted a retrospective, population-based analysis using drug susceptibility testing (DST) results of MDR Mycobacterium tuberculosis complex isolates obtained from 2007-2014 in Taiwan.MethodsM. tuberculosis isolates collected from 1,331 MDR-TB cases were included in this survey. Treatment histories, age, sex, chest radiograph and bacteriological results of patients were analyzed. Standard DST was performed to assess resistance to the following drugs: isoniazid (INH), rifampicin (RIF), streptomycin (SM), ethambutol (EMB), amikacin (AM), kanamycin (KM), capreomycin (CAP), ofloxacin (OFX), moxifloxacin (MOX), levofloxacin (LVX), gatifloxacin (GAT), para-aminosalicylate (PAS), ethionamide (EA), and pyrazinamide (PZA). The Cochran-Armitage trend test was used for statistical analysis.ResultsWe observed a significant increasing trend in portion of new MDR-TB cases, from 59.5% to 80.2% (p < 0.0001), and significant decreasing trend of portion in the 15-44-year-old age group (p < 0.05). Of the MDR M. tuberculosis isolates tested, 6.2% were resistant to AM, 8.6% were resistant to KM, 4.6% were resistant to CAP, 19.5% were resistant to OFX, 17.1% were resistant to MOX, 16.0% were resistant to LVX, 5.8% were resistant to GAT, 9.5% were resistant to PAS, 28.5% were resistant to EA and 33.3% were resistant to PZA. Fifty (3.8%) extensively drug-resistant TB cases were identified. No significant differences were found in drug resistance frequencies between new and previously treated MDR cases. However, we observed significant decreases in the rates of AM resistance (p < 0.05), OFX resistance (p < 0.00001), PAS resistance (p < 0.00001), EA resistance (p < 0.05) and PZA resistance (p < 0.05). Moreover, younger age groups had higher rates of resistance to fluoroquinolones.ConclusionA policy implemented in 2007 to restrict the prescription of fluoroquinolones was shown to be effective. Our survey revealed a decreasing trend of resistance to PZA, OFX and AM, which suggests the feasibility of adopting a short-course regimen and demonstrates the effectiveness of our management program for MDR-TB.

Project description:BackgroundEthiopia is one of the high multidrug-resistant tuberculosis (MDR-TB) burden countries. However, phenotypic drug susceptibility testing can take several weeks due to the slow growth of Mycobacterium tuberculosis complex (MTBC) strains. In this study, we assessed the performance of a Sanger sequencing approach to predict resistance against five anti-tuberculosis drugs and the pattern of resistance mediating mutations.MethodsWe enrolled 226 MTBC culture-positive MDR-TB suspects and collected sputum specimens and socio-demographic and TB related data from each suspect between June 2015 and December 2016 in Addis Ababa, Ethiopia. Phenotypic drug susceptibility testing (pDST) for rifampicin, isoniazid, pyrazinamide, ethambutol, and streptomycin using BACTEC MGIT 960 was compared with the results of a Sanger sequencing analysis of seven resistance determining regions in the genes rpoB, katG, fabG-inhA, pncA, embB, rpsL, and rrs.ResultDNA isolation for Sanger sequencing was successfully extracted from 92.5% (209/226) of the MTBC positive cultures, and the remaining 7.5% (17/226) strains were excluded from the final analysis. Based on pDST results, drug resistance proportions were as follows: isoniazid: 109/209 (52.2%), streptomycin: 93/209 (44.5%), rifampicin: 88/209 (42.1%), ethambutol: 74/209 (35.4%), and pyrazinamide: 69/209 (33.0%). Resistance against isoniazid was mainly mediated by the mutation katG S315T (97/209, 46.4%) and resistance against rifampicin by rpoB S531L (58/209, 27.8%). The dominating resistance-conferring mutations for ethambutol, streptomycin, and pyrazinamide affected codon 306 in embB (48/209, 21.1%), codon 88 in rpsL (43/209, 20.6%), and codon 65 in pncA (19/209, 9.1%), respectively. We observed a high agreement between phenotypic and genotypic DST, such as 89.9% (at 95% confidence interval [CI], 84.2%-95.8%) for isoniazid, 95.5% (95% CI, 91.2%-99.8%) for rifampicin, 98.6% (95% CI, 95.9-100%) for ethambutol, 91.3% (95% CI, 84.6-98.1%) for pyrazinamide and 57.0% (95% CI, 46.9%-67.1%) for streptomycin.ConclusionWe detected canonical mutations implicated in resistance to rifampicin, isoniazid, pyrazinamide, ethambutol, and streptomycin. High agreement with phenotypic DST results for all drugs renders Sanger sequencing promising to be performed as a complementary measure to routine phenotypic DST in Ethiopia. Sanger sequencing directly from sputum may accelerate accurate clinical decision-making in the future.

Project description:The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes.We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes.Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% (n = 275); 58% (n = 272) for MDR-TB and 30% (n = 3) for XDR-TB. Overall, 27% were lost to follow-up (n = 130), 27% (n = 126) for MDR-TB and 40% (n = 4) for XDR-TB; and 16% had a poor treatment outcome (n = 76), 15% for MDR-TB and 30% (n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resistance to ofloxacin was an independent predictor of poor (AHR = 3.1; 95%CI = 1.5, 6.3), and unfavourable (AHR = 1.7; 95%CI = 1.07, 2.9) treatment outcomes. Patients who started treatment during 2011-2012 (AHR = 2.8; 95% CI = 1.5, 5.3) and 2013 (AHR = 2.1; 95% CI = 1.2, 3.9) had poorer treatment outcomes compared to patients who started treatment during 2014.Patients with MDR-TB and XDR-TB had low rates of treatment success in Hunan Province, especially among patients who started treatment during 2011 to 2013, with evidence of improved treatment outcomes in 2014. Resistance to ofloxacin was an independent predictor of poor treatment outcomes.

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Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

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Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.

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