Dataset Information

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

ABSTRACT:

Objective

Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment.

Study design and setting

We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regression, we estimated associations and their 95% confidence intervals (CI) between the outcome of individual deviation in treatment duration (in months) from the mean duration of their treatment site and patient characteristics, drug resistance, and treatments used.

Results

Overall, 6702 patients with successful treatment outcomes from 84 treatment sites were included. We found that factors commonly associated with poor treatment outcomes were also associated with longer treatment durations, relative to the site mean duration. Use of bedaquiline was associated with a 0.51 (95% CI: 0.15, 0.87) month decrease in duration of treatment, which was consistent across subgroups, while MDR/RR-TB with fluoroquinolone resistance was associated with 0.78 (95% CI: 0.36, 1.21) months increase.

Conclusion

We describe a method to assess associations between clinical factors and treatment duration in observational studies of MDR/RR-TB patients, that may help identify patients who can benefit from shorter treatment.

SUBMITTER: Winters N

PROVIDER: S-EPMC10553332 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

Winters Nicholas N Schnitzer Mireille E ME Campbell Jonathon R JR Ripley Susannah S Winston Carla C Savic Rada R Ahmad Nafees N Bisson Gregory G Dheda Keertan K Esmail Ali A Gegia Medea M Monedero Ignacio I Dalcolmo Margareth Pretti MP Rodrigues Denise D Singla Rupak R Yim Jae-Joon JJ Menzies Dick D

PloS one 20231005 10

<h4>Objective</h4>Studying treatment duration for rifampicin-resistant and multidrug-resistant tuberculosis (MDR/RR-TB) using observational data is methodologically challenging. We aim to present a hypothesis generating approach to identify factors associated with shorter duration of treatment.<h4>Study design and setting</h4>We conducted an individual patient data meta-analysis among MDR/RR-TB patients restricted to only those with successful treatment outcomes. Using multivariable linear regre ...[more]

PMID: 37797071

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Project description:BackgroundIn 2016, World Health Organization guidelines conditionally recommended standardised shorter 9-12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8-44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.

Project description:Tuberculosis treatment is challenging, especially among people with drug-resistant forms of tuberculosis. The introduction of fully oral modified short treatment regimen has a great potential to shorten duration of treatment, improve safety and ultimately increase treatment success rate. In 2019 Georgia has piloted the modified fully oral shorter treatment regimen in a routine programmatic condition. Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine. Study patients were enrolled between March-August 2019. We used a national electronic surveillance system, medical records and active TB drug-safety monitoring and management database to extract study related data. The mean age of the study participants was 48 years, 68% were male, 8% were HIV positive, 16% had diabetes and 12% tested positive for hepatitis C infection. The median time to culture conversion among 16 patients who were culture positive at treatment initiation was 1.0 (95% CI: 1.0-2.0) month. Of those, by the end of treatment 15 patients converted to negative. Out of the 25 patients in the study cohort 22 (88%) had successful treatment outcome, one patient (4%) died and two (8%) were lost to follow up. The regimen was largely well tolerated. Three patients (12%) experienced serious adverse events, of which in two cases were possibly related to TB drugs in the regimen. Seven patients developed adverse events of interest in eight instances, including musculoskeletal (twice), psychiatric, gastrointestinal disorders, hepatotoxicity, peripheral neuropathy, cardiotoxicity and myelosuppression (once each). In four patients (16%) the duration of the treatment was extended beyond nine months due to insufficient radiological improvements. Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted.

Project description:BackgroundDrug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens.MethodsWe searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050).ResultWe included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care.ConclusionTreatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.

Project description:BackgroundInterim treatment outcomes at 6-months for multidrug-resistant tuberculosis (MDR-TB) treatment are among the most basic performance monitoring and key evaluation indicators in the Stop and End TB strategy of the World Health Organization (WHO). Therefore, this study was conducted to evaluate the interim treatment outcomes of MDR-TB patients in Pakistan.MethodsThis study was conducted at the Programmatic Management Unit for Drug-resistance TB (PMDT) site of the National Tuberculosis Program (NTP), Pakistan. It is located in the Chest Disease Unit (CDU) of the Bahawal Victoria Hospital (BVH), Bahawalpur, Punjab, Pakistan. Data was collected between April 1, 2014 and December 31, 2015. The medical records, Electronic Nominal Recording Reporting System (ENRS) data and MRD-TB notification forms of the MDR-TB patients registered at the PMDT site were reviewed to obtain data. For reporting and calculation of interim treatment outcomes, standardized WHO methodology was adopted. Simple logistic regression analysis was used to examine the possible association between the dependent variable (i.e. unsuccessful interim treatment outcome) and selected socio-demographic and clinical variables.ResultsA total of 100 drug-resistant TB (DR-TB) patients (all types) were registered during the study period. Out of these, 80 were MDR-TB patients for whom interim results were available. Out of the 80 MDR-TB cases, 48 (60%) were classified under the successful interim treatment outcome category. The remaining 40% had unsuccessful 6-month treatment outcomes and 12 (15%) patients died, while nine (11.3%) were lost to follow-up by six months. The final predictors of unsuccessful interim treatment outcomes were; being resistant to ofloxacin (AOR 3.23, 95% CI 0.96-10.89; p-value = 0.04), having above normal baseline serum creatinine levels (AOR 6.49, 95% CI 1.39-30.27; p-value = 0.02), and being culture positive at the second month of treatment (AOR 6.94, 95% CI 2-24.12; p-value = 0.01).ConclusionsDespite free treatment and programmatic efforts to ensure patient adherence, the high rate of unsuccessful interim treatment outcomes is concerning. The identified risk factors for unsuccessful interim treatment outcomes in the current study provides clinicians an opportunity to identify high-risk patients and ensure enhanced clinical management and greater treatment success rates.

Dataset Information

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

Objective

Study design and setting

Results

Conclusion

Publications

Identifying patients with multidrug-resistant tuberculosis who may benefit from shorter durations of treatment.

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