Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis
Open Access
- 5 August 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Clinical Infectious Diseases
- Vol. 59 (10), 1364-1374
- https://doi.org/10.1093/cid/ciu619
Abstract
The clinical validity of drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line antituberculosis drugs is uncertain. In an individual patient data meta-analysis of 8955 patients with confirmed multidrug-resistant tuberculosis, DST results for these drugs were associated with treatment outcomes. Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.This publication has 49 references indexed in Scilit:
- Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 PatientsPLoS Medicine, 2012
- Randomized Pilot Trial of Eight Weeks of Bedaquiline (TMC207) Treatment for Multidrug-Resistant Tuberculosis: Long-Term Outcome, Tolerability, and Effect on Emergence of Drug ResistanceAntimicrobial Agents and Chemotherapy, 2012
- Treatment Outcomes of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-AnalysisPLOS ONE, 2009
- Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysisThe Lancet Infectious Diseases, 2009
- Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control StudyPLOS ONE, 2008
- Treatment Outcomes for HIV‐Uninfected Patients with Multidrug‐Resistant and Extensively Drug‐Resistant TuberculosisClinical Infectious Diseases, 2008
- Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment FailuresPLOS ONE, 2007
- Randomized Trials to Optimize Treatment of Multidrug-Resistant TuberculosisPLoS Medicine, 2007
- Feasibility and Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the PhilippinesPLoS Medicine, 2006
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002