The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence.This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking.
Background
To assess the validity of sputum culture conversion (SCC) on solid media at varying time points and the time to SCC as prognostic markers for end-of-treatment outcome in multidrug-resistant (MDR) tuberculosis (TB) patients.
Methods
Data on1,712 MDR-TB patients from two large cohort studies were analyzed. Measures of association were determined using random effects multivariable logistic regression. Predictive values were calculated using bivariate random-effects generalized linear mixed model.
Findings
Times to SCC and SCC status at 6 months were significantly associated with treatment success compared to failure or death. SCC status at 2 months was significantly associated with treatment success among patients without known HIV infection only. The overall association of SCC with a successful outcome was substantially stronger at 6 months (adjusted odds ratio [aOR]=14.07, 95% CI 10.05–19.71) than at 2 months (HIV-negative patients: aOR=4.12 [2.25–7.54]; HIV unknown: aOR=3.59 [1.96–6.58], HIV-positive: aOR=0.38 [0.12–1.18]). The 2-month SCC had low sensitivity (27%) and high specificity (90%) for predicting treatment success. Conversely, 6-month SCC status had high sensitivity (92%), but moderate specificity (58%). The maximum combined sensitivity and specificity for SCC was reached between the 6th and 10th month of treatment.
Interpretation
Time to SCC, SCC status at 6 months, and SCC status at 2 months among patients without known HIV infection can be considered proxy markers of end-of-treatment outcome in MDR-TB patients, but the overall association with treatment success is substantially stronger for 6-month compared to 2-month SCC.
Funding
USAID, the US CDC, the Division of Intramural Research of NIAID/NIH, and the Republic of Korea’s CDC.
The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.
Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.