• Compassionate Use of New Drugs in Children and Adolescents with Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Early Experiences and Challenges

      Tadolini, M; Garcia-Prats, AJ; D'Ambrosio, L; Hewison, C; Centis, R; Schaaf, HS; Marais, BJ; Ferreira, H; Caminero, JA; Jonckheere, S; et al. (European Respiratory Society, 2016-06-23)
    • Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

      Mohr, E; Hughes, J; Reuter, A; Trivino Duran, L; Ferlazzo, G; Daniels, J; De Azevedo, V; Kock, Y; Steele, SJ; Shroufi, A; et al. (European Respiratory Society, 2018-06-14)
      Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa. This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF). Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred. This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.
    • Diagnostic sensitivity of SILVAMP TB-LAM (FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV

      Kerkhoff, AD; Sossen, B; Schutz, C; Reipold, EI; Trollip, A; Moreau, E; Schumacher, SG; Burton, R; Ward, A; Nicol, MP; et al. (European Respiratory Society, 2019-11-07)
    • Efficacy, Safety and Tolerability of Linezolid for the Treatment of XDR-TB: a Study in China

      Berry, C; Yates, TA; Seddon, JA; Phillips, PP; du Cros, P (European Respiratory Society, 2016-05-01)
    • Linezolid for multidrug-resistant tuberculosis in HIV-infected and -uninfected patients.

      Hughes, J; Isaakidis, P; Andries, A; Mansoor, H; Cox, V; Meintjes, G; Cox, H (2015-07)
    • Multidrug-Resistant Tuberculosis Treatment Failure Detection Depends on Monitoring Interval and Microbiological Method

      Mitnick, CD; White, RA; Lu, C; Rodriguez, CA; Bayona, J; Becerra, MC; Burgos, M; Centis, R; Cohen, T; Cox, H; et al. (European Respiratory Society, 2016-09-01)
      Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
    • Standardised shorter regimens versus individualised longer regimens for multidrug-resistant TB

      Abidi, S; Achar, J; Neino, M; Bang, D; Benedetti, A; Brode, S; Campbell, J; Casas, E; Conradie, F; Dravniece, G; et al. (European Respiratory Society (ERS), 2019-12-20)
      We sought to compare the effectiveness of two WHO-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis: a standardised regimen of 9-12 months (the "shorter regimen"), and individualised regimens of ≥20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR tuberculosis. We used propensity score matched, mixed-effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRD) for failure or relapse, death within 12 months of treatment initiation, and loss to follow-up.We included 2625/3378 (77.7%) individuals from 9 studies of shorter regimens, and 2717/13104 (20.7%) from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions: 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD, -0.15 95%CI: -0.17 to -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (0.02, 95%CI: 0 to 0.05), and greater in magnitude with baseline resistance to pyrazinamide (0.12, 95%CI: 0.07 to 0.16), prothionamide/ethionamide (0.07, 95%CI: -0.01 to 0.16), or ethambutol (0.09, 95%CI: 0.04 to 0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment as compared to individualised longer regimens, and with more failure/relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
    • Towards tuberculosis elimination: an action framework for low-incidence countries

      Lönnroth, K; Migliori, G B; Abubakar, I; D'Ambrosio, L; de Vries, G; Diel, R; Douglas, P; Falzon, D; Gaudreau, M-A; Goletti, D; et al. (European Respiratory Society, 2015-03-18)
      This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.