scholarly journals Group 5 drugs for multidrug-resistant tuberculosis: individual patient data meta-analysis

2016 ◽  
Vol 49 (1) ◽  
pp. 1600993 ◽  
Author(s):  
Greg J. Fox ◽  
Andrea Benedetti ◽  
Helen Cox ◽  
Won-Jung Koh ◽  
Piret Viiklepp ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Meta Analysis ◽  
Treatment Success ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Amoxicillin Clavulanic Acid ◽  
Group 5

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

scholarly journals Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis

PLoS Medicine ◽  
2018 ◽  
Vol 15 (7) ◽  
pp. e1002591 ◽  
Author(s):  
Elizabeth P. Harausz ◽  
Anthony J. Garcia-Prats ◽  
Stephanie Law ◽  
H. Simon Schaaf ◽  
Tamara Kredo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals Estimating treatment importance in multidrug‐resistant tuberculosis using Targeted Learning: An observational individual patient data network meta‐analysis

Biometrics ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 1007-1016
Author(s):  
Guanbo Wang ◽  
Mireille E. Schnitzer ◽  
Dick Menzies ◽  
Piret Viiklepp ◽  
Timothy H. Holtz ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Meta Analysis ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Data Network ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

scholarly journals WHO Group 5 Drugs and Difficult Multidrug-Resistant Tuberculosis: a Systematic Review with Cohort Analysis and Meta-Analysis

2013 ◽  
Vol 57 (9) ◽  
pp. 4097-4104 ◽  
Author(s):  
Kwok-Chiu Chang ◽  
Wing-Wai Yew ◽  
Cheuk-Ming Tam ◽  
Chi-Chiu Leung
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Cohort Analysis ◽  
Multidrug Resistant ◽  
Favorable Outcome ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Geographical Regions ◽  
Mdr Tb ◽  
Group 5

ABSTRACTIt 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.

scholarly journals Effectiveness and safety of standardised shorter regimens for multidrug-resistant tuberculosis: individual patient data and aggregate data meta-analyses

2017 ◽  
Vol 50 (1) ◽  
pp. 1700061 ◽  
Author(s):  
Faiz Ahmad Khan ◽  
M.A. Hamid Salim ◽  
Philipp du Cros ◽  
Esther C. Casas ◽  
Atajan Khamraev ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Aggregate Data ◽  
Second Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Meta Regression ◽  
Meta Analyses

We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9–90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8–273), pyrazinamide resistance (OR 8, 95% CI 2–38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3–202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.

Sign in / Sign up

Export Citation Format

Share Document