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(MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation.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.

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 The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

scholarly journals Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Second Line ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improper Use ◽  
Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

scholarly journals Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Agibothu Kupparam Hemanth Kumar ◽  
Alok Kumar ◽  
Thiruvengadam Kannan ◽  
Rakesh Bhatia ◽  
Dipti Agarwal ◽  
...  
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Second Line ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

scholarly journals Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis

2016 ◽  
Vol 62 (7) ◽  
pp. 887-895 ◽  
Author(s):  
Gregory J. Fox ◽  
Carole D. Mitnick ◽  
Andrea Benedetti ◽  
Edward D. Chan ◽  
Mercedes Becerra ◽  
...  
Keyword(s):  
Individual Patient Data ◽  
Multidrug Resistant ◽  
Patient Data ◽  
Adjunctive Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis

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 Hepatitis C virus infection: a challenge in the complex management of two cases of multidrug-resistant tuberculosis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Maria Musso ◽  
Silvia Mosti ◽  
Gina Gualano ◽  
Paola Mencarini ◽  
Rocco Urso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Side Effects ◽  
Chronic Infection ◽  
Multidrug Resistant ◽  
Hcv Infection ◽  
Second Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.

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