L Mota1, K Al-Efraij2, J R Campbell3, V J Cook4, F Marra3, J Johnston4. 1. British Columbia Centre for Disease Control, Vancouver, Canada. 2. University of British Columbia, Faculty of Medicine, Division of Respirology, Vancouver, Canada. 3. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 4. British Columbia Centre for Disease Control, Vancouver, University of British Columbia, Faculty of Medicine, Division of Respirology, Vancouver, Canada.
Abstract
BACKGROUND: Therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes, but there is little evidence to guide TDM in clinical practice. DESIGN: We performed a systematic review and meta-analysis to summarise existing literature on TDM in first-line drugs. RESULTS: We identified 41 studies that reported 2 h post-dose drug concentrations (C2h) for first-line drugs and 12 studies that reported clinical outcomes. We pooled data by study quality, design, region, dosing modality and patient characteristics. The pooled proportion of subjects with low isoniazid C2h was 0.43 (95%CI 0.32-0.55), 0.67 (95%CI 0.60-0.74) had low rifampicin C2h, 0.27 (95%CI 0.17-0.38) had low ethambutol C2h, and 0.12 (95%CI 0.07-0.19) had low pyrazinamide C2h. Patients with diabetes had a non-significant increase in the proportion of subjects with low C2h levels across all four drugs. Only three of 12 studies that examined clinical outcomes demonstrated an association between low C2h and unsuccessful treatment outcomes. CONCLUSION: Across a wide variety of studies, a high proportion of patients undergoing first-line anti-tuberculosis treatment had 2 h drug concentrations below the accepted normal threshold. These findings point to a discrepancy between accepted 2 h TDM thresholds and TB drug dosing recommendations.
BACKGROUND: Therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes, but there is little evidence to guide TDM in clinical practice. DESIGN: We performed a systematic review and meta-analysis to summarise existing literature on TDM in first-line drugs. RESULTS: We identified 41 studies that reported 2 h post-dose drug concentrations (C2h) for first-line drugs and 12 studies that reported clinical outcomes. We pooled data by study quality, design, region, dosing modality and patient characteristics. The pooled proportion of subjects with low isoniazidC2h was 0.43 (95%CI 0.32-0.55), 0.67 (95%CI 0.60-0.74) had low rifampicin C2h, 0.27 (95%CI 0.17-0.38) had low ethambutol C2h, and 0.12 (95%CI 0.07-0.19) had low pyrazinamideC2h. Patients with diabetes had a non-significant increase in the proportion of subjects with low C2h levels across all four drugs. Only three of 12 studies that examined clinical outcomes demonstrated an association between low C2h and unsuccessful treatment outcomes. CONCLUSION: Across a wide variety of studies, a high proportion of patients undergoing first-line anti-tuberculosis treatment had 2 h drug concentrations below the accepted normal threshold. These findings point to a discrepancy between accepted 2 h TDM thresholds and TB drug dosing recommendations.
Authors: Roger K Verbeeck; Gunar Günther; Dan Kibuule; Christian Hunter; Tim W Rennie Journal: Eur J Clin Pharmacol Date: 2016-06-15 Impact factor: 2.953
Authors: Giorgia Sulis; Rosella Centis; Giovanni Sotgiu; Lia D'Ambrosio; Emanuele Pontali; Antonio Spanevello; Alberto Matteelli; Alimuddin Zumla; Giovanni Battista Migliori Journal: NPJ Prim Care Respir Med Date: 2016-11-03 Impact factor: 2.871