An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis

Abstract

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

“…While this is currently still out of reach for the majority of patients, it is very likely that the technologies will soon become available for the countries that are most affected by the global burden of MDR‐TB. Bespoke management packages comprising individualized treatment regimens, individualized dosage of anti‐TB drugs, and individualized biomarker‐guided duration of therapy will likely optimize treatment responses, and adherence, whilst minimizing adverse events . Alternative approaches and interventions including different routes of drug administration, TDM, use of efflux inhibitors, and more sensitive diagnostics to detect microheteroresistance will also prevent resistance amplification .…”

“…65,99 The proportion of favourable treatment outcomes was higher in patients undergoing individualized drug therapy when compared to standardized therapies in a large meta-analysis. 119 However, the concept of individualized therapy for M/XDR-TB patients is still not fully exhausted ( Table 5). [100][101][102] Molecular methods for early detection of drug resistance are available in most parts of the world.…”

Recent controversies about MDR and XDR‐TB: Global implementation of the WHO shorter MDR‐TB regimen and bedaquiline for all with MDR‐TB?

“…Thus, be it shorter or conventional, MDR‐TB treatment must move away from purely empiric to more individualized regimens . Moreover, neither the recommended duration of the shorter regimen nor the conventional regimen is ideal for the majority of patients affected by MDR‐TB.…”

“…Thus, be it shorter or conventional, MDR-TB treatment must move away from purely empiric to more individualized regimens. 56 Moreover, neither the recommended duration of the shorter regimen nor the conventional regimen is ideal for the majority of patients affected by MDR-TB. More efforts must be spent to develop individualized regimens through comprehensive and reliable DST and the identification of time point-specific biomarkers indicating relapse-free cure, and when therapy can safely be discontinued.…”

New drugs and regimens for tuberculosis

“…In a recent meta-analysis, individualized MDR-TB treatment regimens achieved higher success rates than standardized counterparts. 70 However, with the major gap in treatment of MDR-TB cases in many highburden but resource-limited areas, the individually tailored 20-month longer regimens might be excessively long for large-scale implementation. 7,9…”