TABLE 1

Characteristics of the 10 multidrug-resistant pulmonary tuberculosis patients exposed to bedaquiline and delamanid treatment

PatientAge yearsTB formResistance profile (in addition to H and R)Bdq-Dlm treatment#Treatment duration with Bdq/Dlm daysTotal treatment duration daysExposure to Bdq and Dlm daysTreatment: non-QT-prolonging drugsTreatment: QT-prolonging drugsMaximum QTcF value ms (months of treatment)Drug discontinued for any adverse event (adverse event)SurgeryTime to sputum culture conversionTreatment outcome
155S+ C+ Cav+ Bil+Z, E, Ofx, Eto, PASConcomitant63/42844848Cs, LzdMfx(400)438 (5)Lzd (optic neuritis)No23Cure
229S− C+ Cav+ Bil−Z, E, S, Ofx, Mfx, Km, Eto, PAS, Cs, BdqConcomitant113/636749180PAS, Am, LzdMfx(800), Cfz459 (21)PAS (vomiting), Am (hearing loss)No55Cure
3§20S+ C+ Cav+ Bil+Z, S, Ofx, Mfx, Am, Km, Cm, Eto, CsConcomitant839/705839705E, PAS, Lzd, Ipm, Amx/Clv421 (5)Yes (lobectomy)80Cure
432S+ C+ Cav+ Bil+Z, E, S, Ofx, Mfx, Eto, PAS, CsConcomitant732/142732147Am, Lzd, Ipm, Amx/ClvCfz,489 (13)Dlm (adrenal insufficiency)Yes (lobectomy)89Cure
546S+ C+ Cav+ Bil−Z, E, S, Ofx, Mfx, Km, Eto, Cs,Concomitant355/324725203Am, Cs, PASMfx(800), Cfz>500 (8)+Mfx(800) (QT prolongation), Am (hearing loss)No73Cure
630S+ C+ Cav+ Bil+Z, E, S, Ofx, Mfx, Eto, LzdConcomitant735/700735700Am, Cs, PAS, Ipm, Amx/ClvCfz>500 (5)Cfz (QT prolongation)No87Cure
733S+ C− Cav+ Bil+Z, E, S, Ofx, Mfx, Am, Km, Cm, Eto, Cs, BdqSequential (20)56/286286160PAS, Lzd, Ipm, Amx/ClvCfz472 (1)NoNaLTFU
836S+ C− Cav+ Bil+Z, E, S, Ofx, Mfx, Km, Cm, Eto, Cs, BdqSequential (71)529/741741109Z, Am, Eto, Ipm, Amx/Clv481 (1)Yes (lobectomy)NaCure
940S+ C+ Cav+ Bil+Z, E, S, Ofx, Mfx, Am, Km, Cm, Eto, BdqSequential (1)67/698744180Cm, Cs, PAS, LzdMfx(800), Cfz447 (11)Lzd (peripheral neuropathy)No39Cure
1025S+ C+ Cav+ Bil+Z, E, S, Ofx, Mfx, EtoSequential (19)426/286731161Am, PAS, Cs, LzdMfx(400), Cfz455 (13)Lzd (peripheral neuropathy), Bdq (oligoarthritis/ osteonecrosis)No88Cure

#: for sequential treatment, time in days from bedaquiline discontinuation to delamanid start is shown in brackets; : exposure was calculated as the sum of concomitant treatment and, for sequential treatment of bedaquiline and delamanid, time until the end of the washout period (180 days for bedaquiline); +: event occurred before the exposure to the bedaquiline/delamanid combination; §: preliminary data of patient 3 have been previously described elsewhere [4]. TB: tuberculosis; QTcF: QT interval corrected according to the Fridericia formula; S+: sputum smear positive at treatment start; S−: sputum smear negative at treatment start; C+: sputum culture positive at treatment start; C−: sputum culture negative at treatment start; Cav+: presence of at least one lung cavity at treatment start; Bil+: bilateral lung involvement at treatment start; Bil−: unilateral lung involvement at treatment start; LTFU: lost to follow-up; R: rifampicin; H: isoniazid; Bdq: bedaquiline; Dlm: delamanid; Z: pyrazinamide; E: ethambutol; S: streptomycin; Ofx: ofloxacin; Mfx(400): moxifloxacin (400 mg·day−1); Mfx(800): moxifloxacin (800 mg·day−1); Am: amikacin; Km: kanamycin; Cm: capreomycin; Eto: ethionamide; Cs: cycloserine; PAS: para-aminosalicylic acid; Lzd: linezolid; Cfz: clofazimine; Ipm: imipenem; Amx/Clv: amoxicillin/clavulanic acid; na: patient was sputum culture negative at treatment start.