Dataset Information

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

ABSTRACT:

Background

Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.

Methods

To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC.

Results

In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance.

Conclusions

Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.

SUBMITTER: Cegielski JP

PROVIDER: S-EPMC4184341 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Publications

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

Cegielski J Peter JP Dalton Tracy T Yagui Martin M Wattanaamornkiet Wanpen W Volchenkov Grigory V GV Via Laura E LE Van Der Walt Martie M Tupasi Thelma T Smith Sarah E SE Odendaal Ronel R Leimane Vaira V Kvasnovsky Charlotte C Kuznetsova Tatiana T Kurbatova Ekaterina E Kummik Tiina T Kuksa Liga L Kliiman Kai K Kiryanova Elena V EV Kim HeeJin H Kim Chang-ki CK Kazennyy Boris Y BY Jou Ruwen R Huang Wei-Lun WL Ershova Julia J Erokhin Vladislav V VV Diem Lois L Contreras Carmen C Cho Sang Nae SN Chernousova Larisa N LN Chen Michael P MP Caoili Janice Campos JC Bayona Jaime J Akksilp Somsak S

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20140723 8

<h4>Background</h4>Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance.<h4>Methods</h4>To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility ...[more]

PMID: 25057101

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Project description:BackgroundResistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.MethodsPatients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.ResultsOf 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.ConclusionsIncreasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

Project description:BackgroundIndividual pharmacokinetic variability may be common in patients treated for multidrug-resistant tuberculosis (MDR-TB) but data are sparse from resource-limited settings and across the early treatment interval.MethodsPlasma drug activity, as measured by the TB Drug Activity (TDA) assay at 2 and 4 weeks of treatment with a standardized MDR-TB regimen was performed in patients with pulmonary MDR-TB from Tanzania. TDA values were correlated with measures of early treatment outcome including every two week collection of sputum for time-to-positivity (TTP) in liquid culture from the MGIT 960 automated system. Patients were evaluated at 24 weeks and those surviving without delayed sputum culture conversion (>8 weeks), culture reversion after previously negative, or weight loss were defined as having a favorable outcome.ResultsTwenty-five patients were enrolled with a mean age of 37 ±12 years. All were culture positive from the pretreatment sputum sample with a mean TTP in MGIT of 257 ±134 hours, and the median time to culture conversion on treatment was 6 weeks. Twenty patients (80%) had an increase in TDA, with the overall mean TDA at 2 weeks of 2.1 ±0.7 compared to 2.4 ±0.8 at 4 weeks (p = 0.005). At 2 weeks 13 subjects (52%) had a TDA value > 2-log killing against their own M. tuberculosis isolate compared to 17 subjects (68%) at 4 weeks (McNemar's exact test p = 0.29). An interim treatment outcome was able to be determined in 23 patients (92%), of whom 7 had a poor outcome (30%). An increase in TDA from week 2 to week 4 was associated with favorable outcome, [unadjusted OR = 20.0, 95% CI: 1.61-247.98, exact p = 0.017 and adjusted OR = 19.33, 95% CI: 1.55-241.5, exact p = 0.023].ConclusionsThe majority of patients with MDR-TB in Tanzania had an increase in plasma drug activity from week 2 to week 4 of treatment as measured by the TDA assay. Understanding the etiology and full impact of this dynamic may inform therapeutic intervention.

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.

Dataset Information

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

Background

Methods

Results

Conclusions

Publications

Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.

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