Figures
- FIGURE 1
Global distribution of multidrug-resistant and extensively drug-resistant tuberculosis cases treated with regimens containing bedaquiline, 2009–2016. n=428 cases in 25 study sites (online supplementary table S1).
- FIGURE 2
Median (interquartile range) values of the Friderica-corrected QT interval (QTcF) and its temporal trends in the cohort in the initial 12 weeks of treatment. Few patients underwent ECG after week 12.
- FIGURE 3
Sputum smear and culture conversion rates of 428 culture-confirmed multidrug-resistant tuberculosis patients exposed to bedaquiline-containing regimens.
Tables
- TABLE 1
Demographic, epidemiological and clinical characteristics of 428 culture-confirmed multidrug-resistant tuberculosis (MDR-TB) patients exposed to bedaquiline-containing regimens
Age years 35 (27–44) Male 263/428 (61.5) Body weight at admission kg 56 (47–65) Height cm 169 (160–176) Migrant 45/428 (10.5) Employed 110/413 (26.6) Prisoner 23/413 (5.6) Pregnant 1/133 (0.8) Thyroid disease 12/413 (2.9) Heart disease 40/318 (12.6) Pre-existing ECG abnormality 13/318 (4.1) Alcoholism 132/363 (36.4) Drug abuse 75/413 (18.2) Methadone use 0/318 (0.0) Diabetes 26/413 (6.3) HIV infection testing 425/428 (99.3) HIV-positive 94/425 (22.1) CD4 count at baseline cells·mm-3 269 (168–470) Nadir CD4+ cell count cells·mm-3 222 (160–402) Antiretroviral therapy exposure 92/94 (97.9) Prior anti-TB therapy 334/428 (78.0) Prior courses of treatment lasting >1 month n 2 (1–2) Prior TB treatment outcome Success 68/263 (25.9) Cure 41/263 (15.6) Completion 27/263 (10.3) Default 35/263 (13.3) Transfer out 20/263 (7.6) Failure 140/263 (53.2) Pulmonary surgery 55/423 (13.0) Previous MDR-TB 169/317 (53.3) Pulmonary involvement 426/428 (99.5) Extrapulmonary involvement 11/428 (2.6) Radiology involvement Cavitary lesion 81/331 (24.5) Bilateral pulmonary with cavitary lesions 147/331 (44.4) Bilateral pulmonary 56/331 (16.9) Noncavitary nonbilateral pulmonary 47/331 (14.2) Sputum smear positive 305/423 (72.1) Sputum culture positive 421/428 (98.4) Drug resistance Streptomycin 185/196 (94.4) Ethambutol 186/240 (77.5) Pyrazinamide 145/206 (70.4) Fluoroquinolones 267/414 (64.5) Amikacin 131/295 (44.4) Capreomycin 127/305 (41.6) Kanamycin 179/302 (59.3) Ethionamide 135/226 (59.7) Cycloserine 20/163 (12.3) Para-aminosalicylic acid 70/196 (35.7) Linezolid 4/38 (10.5) Rifabutin 32/35 (91.4) XDR-TB 195/428 (45.6) MDR- or XDR-TB contacts 105/411 (25.6) Hospital stay days 179 (92–280) Data are presented as median (interquartile range) or n/N (%). XDR-TB: extensively drug-resistant tuberculosis.
- TABLE 2
Safety and tolerability profile of bedaquiline-containing regimens in a cohort of 428 culture-confirmed multidrug-resistant tuberculosis patients
Interruption of bedaquiline 51/428 (11.9) Interruption of bedaquiline due to adverse events 25/428 (5.8) Adverse events presumably due to bedaquiline 80/213 (19.4) Bedaquiline restarted if interrupted 25/69 (36.2) Total bedaquiline exposure days 168 (86–180) Creatinine >1.4×ULN 91/411 (22.1) Lipase >1.6×ULN 1/239 (0.4) ALT >3×ULN 92/413 (22.3) Bilirubin >2×ULN 47/413 (11.4) Albumin g·dL−1 36 (30–40) Potassium <3.4 or >5.6 mmol·L−1 98/412 (23.8) Magnesium <0.59 mmol·L−1 21/199 (10.6) Calcium <1.75 mmol·L−1 23/302 (7.6) Adverse effects Nausea 130/413 (31.5) Peripheral neuropathy 96/412 (23.3) Otovestibular toxicity 96/412 (23.3) Vomiting 87/411 (21.2) Anaemia 86/412 (20.9) Arthralgia 84/412 (20.4) Skin rash 63/412 (15.3) Diarrhoea 56/412 (13.6) Renal failure 47/413 (11.4) Thrombocytopenia 41/413 (9.9) Neutropenia 40/413 (9.7) Lymphocytopenia 40/413 (9.7) QT prolongation 24/248 (9.7) Hypothyroidism 38/410 (9.3) Psychiatric disorder 29/413 (7.0) Tendinopathy 18/413 (4.4) Optic neuropathy 10/413 (2.4) Deep vein thrombosis 7/412 (1.7) Pancreatitis 4/318 (1.3) Hallucinations 2/411 (0.5) Stroke 1/318 (0.3) Data are presented as n/N (%) or median (interquartile range). ULN: upper limit of normal; ALT: alanine-transaminase.
- TABLE 3
Treatment outcome and conversion rates of culture-confirmed multidrug-resistant tuberculosis (MDR-TB) patients exposed to bedaquiline-containing regimens and treatment outcomes of MDR-TB patients starting their treatment with bedaquiline-containing regimens before December 31, 2014
Bedaquiline-containing regimen Bedaquiline-containing regimen started before December 31, 2014 Patients n 428 130 Sputum smear conversion 30 days 206/324 (63.6) Sputum culture conversion 30 days 117/389 (30.1) Sputum smear conversion 60 days 257/317 (81.1) Sputum culture conversion 60 days 213/376 (56.7) Sputum smear conversion 90 days 265/310 (85.5) Sputum culture conversion 90 days 298/370 (80.5) Sputum smear conversion at the end of treatment 126/140 (90.0) Sputum culture conversion at the end of treatment 191/208 (91.8) Time to sputum smear conversion days 4 (30–60) Time to sputum culture conversion days 60 (33–90) Treatment outcome Success 176/247 (71.3) 100/130 (76.9) Cure 154/247 (62.4) 86/130 (66.2) Completion 22/247 (8.9) 14/130 (10.8) Death 33/247 (13.4) 8/130 (6.2) Default 18/247 (7.3) 6/130 (4.6) Failure 19/247 (7.7) 16/130 (12.3) Transfer out 1/247 (0.4) Duration of treatment after MDR-TB diagnosis months 18 (10–22) Body weight at end of treatment kg 61.9±13.9 Data are presented as n/N (%), median (interquartile range) or mean±sd, unless otherwise stated.
- TABLE 4
Treatment outcomes of 428 culture-confirmed multidrug resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) patients exposed to bedaquiline-containing regimens in different settings and stratified by cohort
Africa Eastern Europe Other settings 2008–2009 2010–2011 2012–2014 Total cohort 113 85 49 9 121 Success 73 (64.6) 65 (76.5) 38 (77.6) 5 (55.6) 95 (78.5) Cure 73 (64.6) 54 (63.5) 27 (55.1) 5 (55.6) 81 (66.9) Completion 11 (12.9) 11 (22.5) 0 (0.0) 14 (11.6) Death 27 (23.9) 3 (3.5) 3 (6.1) 2 (22.2) 6 (5.0) Default 9 (8.0) 8 (9.4) 1 (2.0) 2 (22.2) 4 (3.3) Failure 3 (2.7) 9 (10.6) 7 (14.3) 0 (0.0) 16 (13.2) Transfer out 1 (0.9) MDR-TB 62 39 27 Success 36 (58.1) 28 (71.8) 22 (81.5) Cure 36 (58.1) 20 (51.3) 11 (40.7) Completion 8 (20.5) 11 (40.7) Death 17 (27.4) 3 (7.7) 1 (3.7) Default 7 (11.3) 3 (7.7) 1 (3.7) Failure 1 (1.6) 5 (12.8) 3 (11.1) Transfer out 1 (1.6) XDR-TB 51 46 22 Success 37 (72.6) 37 (80.4) 16 (72.7) Cure 37 (72.6) 34 (73.9) 16 (72.7) Completion 3 (6.5) Death 10 (19.6) 2 (9.1) Default 2 (3.9) 5 (10.9) Failure 2 (3.9) 4 (8.7) 4 (18.2) Transfer out Data are presented as n or n (%).
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary table S1 ERJ-00387-2017_Supplementary_table_S1
Supplementary Material
Onno Akkerman ERJ-00387-2017_Akkerman
Luigi Codecasa ERJ-00387-2017_Codecasa
M-C. Payen ERJ-00387-2017_Payen
E. Pontali ERJ-00387-2017_Pontali
