High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen.
Norbert NdjekaKathryn SchnippelIqbal MasterGraeme MeintjesGary MaartensRodolfo RomeroXavier PadanilamMartin EnweremSunitha ChotooNalini SinghJennifer A HughesEbrahim VariavaHannetjie FerreiraJulian Te RieleNazir IsmailErika MohrNonkqubela BantubaniFrancesca ConradiePublished in: The European respiratory journal (2018)
South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27-42). 134 (67.0%) were living with HIV; the median CD4+ count was 281 cells·μL-1 (IQR 130-467) and all were on antiretroviral therapy.16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1).Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.
Keyphrases
- drug resistant
- multidrug resistant
- end stage renal disease
- mycobacterium tuberculosis
- acinetobacter baumannii
- newly diagnosed
- ejection fraction
- chronic kidney disease
- gram negative
- prognostic factors
- adipose tissue
- peritoneal dialysis
- atrial fibrillation
- antiretroviral therapy
- oxidative stress
- mass spectrometry
- heart failure
- randomized controlled trial
- emergency department
- type diabetes
- cell death
- escherichia coli
- preterm infants
- human immunodeficiency virus
- induced apoptosis
- skeletal muscle
- mitral valve
- hiv infected
- cystic fibrosis
- south africa
- signaling pathway
- combination therapy
- replacement therapy