The addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks, as compared with placebo. There were more deaths in the bedaquiline group than in the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208 ClinicalTrials.gov number, NCT00449644.).

Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB. @ERSpublications Bedaquiline safety data in a broad patient population treated for drug-resistant TB including XDR-TB (C209 study)

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.

To halt the global tuberculosis epidemic, transmission must be stopped to prevent new infections and new cases. Identification of individuals with tuberculosis and prompt initiation of effective treatment to rapidly render them non-infectious is crucial to this task. However, in settings of high tuberculosis burden, active case-finding is often not implemented, resulting in long delays in diagnosis and treatment. A range of strategies to find cases and ensure prompt and correct treatment have been shown to be effective in high tuberculosis-burden settings. The population-level effect of targeted active case-finding on reducing tuberculosis incidence has been shown by studies and projected by mathematical modelling. The inclusion of targeted active case-finding in a comprehensive epidemic-control strategy for tuberculosis should contribute substantially to a decrease in tuberculosis incidence.

Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.