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The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 µg/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single close of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase., After AIDS, tuberculosis (TB) is the leading cause of infectious disease mortality in the world, with 2 million to 3 million deaths per year (1). The TB and HIV epidemics [...]

Tuberculosis (TB) control programmes of many low TB incidence countries of the European Union/European Economic Area (EU/EEA) perceive challenges in controlling TB due to high numbers of TB in migrants from high-incidence countries. To assess the extent of TB transmission from the foreign-born to the native-born population, we quantitatively investigated the dynamics of TB transmission between these populations in the EU/EEA, using published molecular epidemiological studies. We searched PubMed and EMBASE databases from 1990 to August 2012. We identified 15 studies performed during 1992-2007 covering 12,366 cases, of which median (range) 49.2% (17.7%-86.4%) were foreign-born. The proportion of clustered isolates ranged between 8.5% and 49.1% of the total number of TB cases genotyped and among these, foreign-born cases were equally or more likely to have unique isolates compared to native-born cases. One third of the clusters were "mixed", i.e. composed of foreign- and native-born cases, involving 0-34.2% of all genotyped cases. Cross-transmission among foreign and native populations was bidirectional, with wide differences across studies. This systematic review provides evidence that TB in a foreign-born population does not have a significant influence on TB in the native population in EU/EEA.

We conducted a systematic review and meta-analysis to assess the evidence for the postulation that inappropriate tuberculosis (TB) regimens are a risk for development of multidrug-resistant (MDR)-TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Cohort studies including TB patients who received treatment were selected and data on treatment regimen, drug susceptibility testing results and genotyping results before treatment and at failure or relapse were abstracted from the articles. Four studies were included in the systematic review and two were included in the meta-analysis. In these two studies the risk of developing MDR-TB in patients who failed treatment and used an inappropriate treatment regimen was increased 27-fold (RR 26.7, 95% CI 5.0-141.7) when compared with individuals who received an appropriate treatment regimen. This review provides evidence that supports the general opinion that the development of MDR-TB can be caused by inadequate treatment, given the drug susceptibility pattern of the Mycobacterium tuberculosis bacilli. It should be noted that only two studies provided data for the meta-analysis. The information can be used to advocate for adequate treatment for patients based on drug resistance profiles.

Treating tuberculosis (TB) patients with inappropriate treatment regimens can lead to treatment failure and, thus, patients who have not been cured and/or to the development of (multi)-drug resistance. A systematic review was performed to assess the knowledge of appropriate TB drug regimens among all categories of healthcare workers (HCWs). In January 2011, MEDLINE, EMBASE and other databases were searched for relevant articles. Observational studies published as of the year 2000 that assessed HCW knowledge of TB treatment were selected. A treatment regimen, drug dosage or treatment duration was considered inappropriate if it was not recommended by national guidelines or by the World Health Organization (WHO). Of 1,896 studies, 31 were included from 14 different countries. No study was performed in Europe. In all studies, HCWs with inappropriate knowledge of treatment regimens (8-100%) or treatment duration (5-99%) were observed. The few studies providing detailed data showed that HCWs mainly reported giving treatment regimens with too many drugs and for too long. Knowledge of appropriate doses was also insufficient in most studies. The available studies show that there is a lack of knowledge of national or international TB treatment guidelines and recommendations. Generalisation of the findings to other settings and countries should be done with caution.