• Correspondence regarding "Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa".

      Mohr-Holland, E; Reuter, A; Hughes, J; Daniels, J; Beko, B; Makhanda, G; De Avezedo, V; Kock, Y; Cox, H; Furin, J; et al. (European Respiratory Society, 2020-07-23)
    • Effectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses

      Ahmad Khan, F; Salim, M; du Cros, P; Casas, E; Khamraev, A; Sikhondze, W; Benedetti, A; Bastos, M; Lan, Z; Jaramillo, E; et al. (European Respiratory Society, 2017-07-27)
      We assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.
    • High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

      Ndjeka, N; Schnippel, K; Master, I; Meintjes, G; Maartens, G; Romero, R; Padanilam, X; Enwerem, M; Chotoo, S; Singh, N; et al. (European Respiratory Society, 2018-10-25)
      Background: South African patients with rifampicin-resistant tuberculosis and resistance to fluoroquinolones and/or injectables (pre/XDR-TB) were granted access to bedaquiline through a Clinical Access Programme with strict inclusion and exclusion criteria.Methods: Pre/XDR-TB and XDR-TB patients were treated with 24 weeks bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed.Results: 200 patients were enrolled: 87 (43.9%) with XDR-TB, 99 (49.3%) were female, median age 34 years (IQR 27, 42). 134 (67.0%) were living with HIV; median CD4+ 281 (IQR 130; 467) and all on antiretroviral therapy.16/200 patients (8.0%) did not complete 6 months of bedaquiline of which 8 were lost to follow up, 6 died, 1 stopped for side effects and 1 patient was diagnosed with drug-sensitive TB.146/200 (73.0%) patients had favourable outcomes: 139/200 were cured (69.5%) and 7 completed treatment (3.5%). 25 died (12.5%), were lost from treatment (10.0%), 9 had treatment failure (4.5%).22 adverse events were attributed to bedaquiline: including QTcF >500 ms (n=5), QTcF increase >50 ms from baseline (n=11), paroxysmal atrial flutter (n=1).Conclusion: Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this MDR-TB and XDR-TB cohort.
    • Shortened Multidrug-Resistant Tuberculosis Treatment in Settings with a High Prevalence of Ofloxacin Resistance

      Guglielmetti, L; Varaine, F; Huerga, H; Bonnet, M; Rich, M; Mitnick, C (European Respiratory Society, 2017-07-20)
    • Standardised shorter regimens individualised longer regimens for rifampin- or multidrug-resistant tuberculosis.

      Abidi, S; Achar, J; Neino, MMA; Bang, D; Benedetti, A; Brode, S; Campbell, JR; Casas, EC; Conradie, F; Dravniece, G; et al. (European Respiratory Society, 2020-03-20)
      We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): 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-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals 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- -0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.
    • WHO 2019 guidelines on drug-resistant tuberculosis treatment: based on evidence or expert opinion?

      Guglielmetti, L; Huerga, H; Khan, U; Varaine, F (European Respiratory Society, 2020-03-05)