New drugs and perspectives for new anti-tuberculosis regimens.

Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens. The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply. With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis.

Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

Tuberculosis diagnostic delay and therapy outcomes of non-national migrants in Tel Aviv, 1998-2008.

Non-national migrants have limited access to medical therapy. This study compares diagnostic delay and treatment outcomes of non-insured non-national migrants (NINNM) with insured Israeli citizens (IC) in the Tel Aviv tuberculosis (TB) clinic between 1998 and 2008. Patient delay was the time from symptoms onset to doctor's visit, while system delay was measured from doctor visit to anti-TB therapy administration. We randomly sampled 222 NINNM and 265 IC. NINNM were younger than IC, had lower male to female ratio and fewer smoked. They had less drug/alcohol abuse, more cavitations on chest radiography, longer patient and shorter system delay. Mean patient and system delays of all patients were 25 ± 14 and 79 ± 42 days, respectively. In multivariate analysis, being NINNM, asymptomatic or smoking predicted longer patient delay, while being asymptomatic or having additional co-morbidity predicted longer system delay. Treatment success in sputum smear-positive pulmonary TB NINNM was 81% and 95.7% in IC (p=0.01). Treatment success was not associated with patient or system delay. In multivariate analysis, work security and treatment adherence predicted treatment success. NINNM had longer patient delay and worse therapy outcome, while IC had longer system delay. Both delays should be reduced. NINNM should be informed that TB therapy is free and unlinked with deportation.