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The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71; P ‫؍‬ 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%; P ‫؍‬ 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 ‫؍‬ 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs. M ultidrug-resistant (MDR) tuberculosis (TB) is a serious form of TB and the term MDR implies resistance to at least the essential first-line agents isoniazid (INH) and rifampin (RMP); because INH and RMP are no longer effective, patients with MDR pulmonary TB must be treated for at least 20 months with potentially toxic, less efficacious drugs (20). MDR Mycobacterium tuberculosis isolates will frequently also be resistant to the other first-line drugs pyrazinamide (PZA), ethambutol (EMB), or streptomycin (or SM) and, at times, other drugs such as ethionamide (Eth), a fluoroquinolone, or injectable drugs such as kanamycin (KAN), amikacin, or capreomycin (CAP). MDR TB with additional resistance to the last two mentioned classes is termed extensively drug-resistant (XDR). The spread of MDR TB, particularly among communities with a high prevalence of human immunodeficiency virus (HIV) infection, is threatening the foundations of TB control programs worldwide (19). TMC207, recently renamed bedaquiline, is a diarylquinoline with a novel mode of action specifically inhibiting mycobacterial ATP synthase (1).The present randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of bedaquiline when it is added to a background regimen (BR) in newly d...

Tuberculous meningitis starts with nonspecific symptoms and is often only diagnosed when brain damage has already occurred. Earlier diagnosis will improve outcome significantly. We were able to identify presenting variables independently associated with poor clinical outcome.

One of the obstacles in discussing childhood tuberculosis (TB) is the lack of standard descriptive terminology to classify the diverse spectrum of disease. Accurate disease classification is important, because the correct identification of the specific disease entity has definite prognostic significance. Accurate classification will also improve study outcome definitions and facilitate scientific communication. The aim of this paper is to provide practical guidelines for the accurate radiological classification of intra-thoracic TB in children less than 15 years of age. The proposed radiological classification is based on the underlying disease and the principles of pathological disease progression. The hope is that the proposed classification will clarify concepts and stimulate discussion that may lead to future consensus.

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Background Case fatality ratios among children with tuberculosis disease are poorly understood, particularly among HIV-infected cases and those not receiving tuberculosis treatment. Methods We carried out a systematic review of the published literature to identify studies of population-representative samples of pediatric (<15 years old) tuberculosis cases. We used random effects meta-analysis to produce pooled estimates of case fatality ratios. We stratified our analyses by whether or not children received tuberculosis treatment, age (0–4 years, 5–14 years), and HIV status. Findings We identified 31 papers comprising 35 datasets representing 82,436 children with tuberculosis disease, of whom 9,273 died. Among children with tuberculosis from the pretreatment era, the pooled case fatality ratio was 21.9% (95% confidence interval [CI]: 18.1%, 26.4%). The pooled case fatality ratio was significantly higher among children aged 0–4 years (43.6%; 95% CI: 36.8%, 50.6%) than among children aged 5–14 years (14.9%; 95% CI: 11.5%, 19.1%). In recent studies where the majority of children had tuberculosis treatment, the pooled case fatality ratio was 0.9% (95% CI: 0.5%, 1.6%). USA surveillance data suggest a substantially higher case fatality ratio among HIV-infected children receiving TB treatment, compared with HIV-uninfected children, especially without antiretroviral treatment. Interpretation Without adequate treatment, children with tuberculosis disease, especially those under five years of age, are at high risk of death. HIV-infected children have an increased mortality risk, even when receiving tuberculosis treatment. Funding US National Institutes of Health, Janssen Global Public Health

Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.