New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects.

BACKGROUND: Drug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco.
METHODS: It is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco.
RESULTS: In our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients\' age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327-14.292]).
CONCLUSIONS: Treatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

New-onset clinical or radiological symptoms in a patient with tuberculosis pose diagnostic treatment challenges, which can be due to treatment failure, disease relapse, or paradoxical response. We describe an adolescent case of recurrent paradoxical response complicating tuberculous meningitis. The first paradoxical tuberculosis presented as chest wall abscess, which was complicated by uniocular, gradually progressive, painless loss of vision after 6 months.

Tuberculosis (TB) is a serious major health concern that has existed from millennia. According to annual WHO report 2016, it is considered as world\'s ninth highest killer disease by single infectious agent, ranking above HIV/AIDS. To worsen the scenario the development of multi-drug resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB) have significantly reduced the success rate of TB treatment. Several efforts are being made to handle pharmacodynamic resistance (MDR and XDR-TB) involving designing of new inhibitors, targeting mutated target or by multi-targeting agents. However, the issue of pharmacokinetic resistance in TB is not being addressed appropriately till date. Pharmacokinetic mode of resistance involves an intrinsic mechanism of bacterial drug resistance via expression of various enzymes and efflux pumps that are responsible for the loss of activity of the therapeutic agents. Mycobacterium tuberculosis is also intrinsically resistant to various approved agents via pharmacokinetic mechanism of resistance. Several bacterial enzymes are encoded that either degrade or modifies the drugs and renders them ineffective. Targeting such inactivating bacterial enzymes provides a novel approach to make the current therapy effective and combat the problem of resistance. This review provides an insight into different bacterial enzymes which are responsible for pharmacokinetic drug resistance in TB. The structure attributes and mechanism of catalysis employed by these enzymes to inactivate drug have also been discussed which may provide basis for developing novel therapeutic agents for resistant TB.

Tuberculosis (TB) in a major health problem in the world. WHO and its partners especially, the stop TB partnership launched numerous strategies against TB especially in the 1990. Strategy DOTS (directly observed therapy short course) was launched in 1995. One main key was the direct supervision of drug intake by patients. Progress was achieved but it was insufficient. A new strategy called \"Stop TB Strategy 2006-2015\" was launched in 2006 in the context of Millennium Development Goals (MDG) elaborated by United Nations. The common goals were to halt and start to reverse the incidence of TB, reduce the prevalence and death rate by 50% compared to their level in 1990 by 2015 to eliminate TB as a public health problem by 2050. The end of 2010 marks the mid-point of the Global Plan and is an obvious time to update it and take into account actual progress with a focus on the 2015 to reach goals. So an updated Global Plan to stop TB 2011-2015, was launched. Expected progress and targets were defined for 2015, in diagnosis and treatment, in co-infection TB/HIV, in drug-resistant TB and achievements expected in new tests for diagnosis, new medications, new vaccines and new regimens with shorter duration of treatment. WHO and partners have started discussions to define the new post 2015 strategy to TB control and elimination. Risk factors (diabetes, malnutrition, tobacco smoke…) and socioeconomic factors, which are associated with TB, should be included in the new strategy to eliminate TB in 2050.