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WHO group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis.

ABSTRACT: It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in treatment of 162 (84%) patients, macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10% to 124%) and 55% (10% to 121%), respectively. Defining significant associations by risk ratios ? 1.2 or ? 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other group 5 drugs with respect to outcome for patients treated with linezolid, although selection bias might have led to underestimation of their effects. Our findings substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.

SUBMITTER: Chang KC

PROVIDER: S-EPMC3754286 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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WHO group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis.

Chang Kwok-Chiu KC Yew Wing-Wai WW Tam Cheuk-Ming CM Leung Chi-Chiu CC

Antimicrobial agents and chemotherapy 20130617 9

It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favo ...[more]

PMID: 23774431

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Project description:BackgroundMultidrug-resistant tuberculosis (MDR-TB) in HIV infected individuals is a serious threat to global efforts to combat tuberculosis. Inconsistent findings on the association between HIV infection and MDR-TB were present in many studies. We aimed to review existing data on the relationship between HIV infection and MDR-TB systematically to assess the contribution of HIV on MDR-TB worldwide. We also investigated the patterns of MDR-TB by age, country-wise income, study designs, and global regions.MethodsWe utilized PubMed, Google Scholar, and ScienceDirect databases to select eligible studies for meta-analysis that were published between January 12,010, and July 30, 2020. The random-effects model was used to obtain the pooled odds ratio of the crude association between HIV and MDR-TB with a 95% confidence interval. We investigated the potential publication-bias by checking funnel plot asymmetry and using the Egger's test. Moreover, we assessed the heterogeneity using the I2 statistic. Sensitivity analysis was performed based on sample size and adjustment factors. The protocol was registered with PROSPERO-CRD42019132752.ResultsWe identified 1603 studies through a database search, and after subsequent eliminations we selected 54 studies including 430,534 TB patients. The pooled odds of MDR-TB was 1.42 times higher in HIV-positive patients than HIV-negative patients (OR=1.42,CI=1.17-1.71, I2=75.8%). Subgroup analysis revealed that the estimated pooled odds for South-East Asian countries was 1.86, which is the highest in WHO regions (OR=1.86,CI=1.30-2.67, I2=0.00%), followed by Europe and Africa. The effect estimate was found to be higher for primary MDR-TB (OR=2.76,CI=1.70-4.46, I2=0.00%). There was also a trend towards increased odds of MDR-TB for HIV patients older than 40 years (OR=1.56,CI=1.17-2.06). The association was found to be significant in high-burden TB countries (OR=1.75, CI=1.39-2.19) and in high-income countries (OR=1.55, CI=1.06-2.27).ConclusionSuch findings indicate that HIV infection raises the risk of MDR-TB, and after contrasting it with the results of the earlier pooled study, it appeared to be an upward risk trend. Moreover, we found that the risk is the highest in the South-East Asian region. A balanced allocation of resources is needed to halt both primary and secondary MDR-TB, particularly in HIV infected people with 40 years of age and older.

Project description:BackgroundThe rate of multidrug-resistant tuberculosis is increasing at an alarming rate throughout the world. It is becoming an emerging public health problem in East Africa. The prevalence of multidrug-resistant tuberculosis among pulmonary tuberculosis positive individuals in the region has not been thoroughly investigated.AimThe aim of this systematic review and meta-analysis is to estimate the pooled prevalence of multidrug-resistant tuberculosis among newly diagnosed and previously treated pulmonary tuberculosis cases in East African countries.MethodsEnglish published articles were systematically searched from six electronic databases: PubMed, EMBASE, Scopus, Science direct, Web of Science, and Google scholar. The pooled prevalence of multidrug-resistant tuberculosis and associated risk factors were calculated using Der Simonian and Laird's random Effects model. Funnel plot symmetry visualization confirmed by Egger's regression asymmetry test and Begg rank correlation methods was used to assess publication bias. A total of 16 articles published from 2007 to 2019 were included in this study. STATA 14 software was used for analysis.ResultsOut of 1025 articles identified citations, a total of 16 articles were included in final meta-analysis. The pooled prevalence of multidrug-resistant tuberculosis among newly diagnosed tuberculosis cases and previously treated tuberculosis patients was 4% (95%CI = 2-5%) and 21% (95%CI: 14-28%), respectively. Living conditions, lifestyles (smoking, alcohol use, and drug abuse), previous medical history, diabetes history, and human immunodeficiency virus infection were risk factors contributing to the higher prevalence of multidrug-resistant tuberculosis in East Africa.ConclusionThe review found a significant prevalence of multidrug-resistant tuberculosis in the region. An early diagnosis of tuberculosis and rapid detection of drug-resistant Mycobacterium tuberculosis is a critical priority to identify patients who are not responding to the standard treatment and to avoid transmission of resistant strains. It is also very important to strengthen tuberculosis control and improve monitoring of chemotherapy.

Project description:ImportanceThe management of multidrug-resistant tuberculosis (MDR-TB) during pregnancy is challenging, yet no systematic synthesis of evidence has accurately measured treatment outcomes.ObjectiveTo systematically synthesize treatment outcomes and adverse events among pregnant patients with MDR-TB.Data sourcesPubMed, Scopus, Web of Science, and ProQuest were searched from the inception of each database through August 31, 2021.Study selectionStudies containing cohorts of pregnant patients with a defined treatment outcome were eligible.Data extraction and synthesisIndependent reviewers screened studies and assessed the risk of bias. The study followed the Preferring Reporting Items for Systematic Review and Meta-analyses reporting guideline. Meta-analysis was performed using random-effects models. The sources of heterogeneity were explored through metaregression.Main outcomes and measuresThe primary outcome was the proportion of patients with each treatment outcome (including treatment success, death, loss to follow-up, and treatment failure), and the secondary outcomes included the proportion of patients experiencing adverse events during pregnancy.ResultsIn this systematic review and meta-analysis, 10 studies containing 275 pregnant patients with available data on treatment outcomes were included. The pooled estimate was 72.5% (95% CI, 63.3%-81.0%) for treatment success, 6.8% (95% CI, 2.6%-12.4%) for death, 18.4% (95% CI, 13.1%-24.2%) for loss to follow-up, and 0.6% (95% CI, 0.0%-2.9%) for treatment failure. Treatment success was significantly higher in studies in which the proportion of patients taking linezolid was greater than the median (20.1%) compared with studies in which this proportion was lower than the median (odds ratio, 1.22; 95% CI, 1.05-1.42). More than half of the pregnant patients (54.7%; 95% CI, 43.5%-65.4%) experienced at least 1 type of adverse event, most commonly liver function impairment (30.4%; 95% CI, 17.7%-45.7%), kidney function impairment (14.9%; 95% CI, 6.2%-28.3%), hypokalemia (11.9%; 95% CI, 3.9%-25.6%), hearing loss (11.8%; 95% CI, 5.5%-21.3%), gastrointestinal disorders (11.8%; 95% CI, 5.2%-21.8%), psychiatric disorders (9.1%; 95% CI, 2.5%-21.6%), or anemia (8.9%; 95% CI, 3.6%-17.4%). The pooled proportion of favorable pregnancy outcomes was 73.2% (95% CI, 49.4%-92.1%). The most common types of adverse pregnancy outcomes were preterm birth (9.5%; 95% CI, 0.0%-29.0%), pregnancy loss (6.0%; 95% CI, 1.3%-12.9%), low birth weight (3.9%; 95% CI, 0.0%-18.7%), and stillbirth (1.9%; 95% CI, 0.1%-5.1%). Most of the studies had low-quality (3 studies) or medium-quality (4 studies) scores.Conclusions and relevanceIn this systematic review and meta-analysis, high treatment success and favorable pregnancy outcomes were reported among pregnant patients with MDR-TB. Further research is needed to design shorter, more effective, and safer treatment regimens for pregnant patients with MDR-TB.

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WHO group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis.

Publications

WHO group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis.

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