@article{fdi:010070864,
  title = {{E}ffects on the {QT} interval of a gatifloxacin-containing regimen versus standard treatment of pulmonary tuberculosis},
  author = {{O}lliaro, {P}. {L}. and {M}erle, {C}. and {M}thiyane, {T}. and {B}ah, {B}. and {K}assa, {F}. and {A}mukoye, {E}. and {N}'{D}iaye, {A}. and {P}erronne, {C}. and {L}ienhardt, {C}hristian and {M}c{I}lleron, {H}. and {F}ielding, {K}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he effects on ventricular repolarization-recorded on the electrocardiogram ({ECG}) as lengthening of the {QT} interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. {A} correction factor ({QT}c) is introduced to make the {QT} independent of the heart rate, translating into the slope of the regression line between {QT} and heart rate being close to zero. {ECG}s were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the {OFLOTUB} study, a randomized controlled trial conducted in five {A}frican countries. {D}rug levels were measured at steady state (month 1) in a subset of patients. {W}e compared treatment effects on the {QT}c and modeled the effect of individual drugs' maximum concentrations of drug in serum ({C}-max) on the {F}ridericia-corrected {QT} interval. {A} total of 1,686 patients were eligible for the correction factor analysis of {QT} at baseline (mean age, 30.7 years; 27% female). {M}edian heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5 degrees {C}. {P}retreatment, the nonlinear model estimated the best correction factor at 0.4081 in between {B}azett's (0.5) and {F}ridericia's (0.33) corrections. {O}n treatment, {F}ridericia ({QT}c{F}) was the best correction factor. {A} total of 1,602 patients contributed to the analysis of {QT}c{F} by treatment arm. {T}he peak {QT}c{F} value during follow-up was > 480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and > 500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% confidence interval [{CI}], -2.0% to 2.3%; {P} = 0.12) and 0.1% (95% {CI}, -0.6% to 0.9%; {P} = 0.75), respectively, between the test and control arms. {O}ne hundred six (6.6%) patients had a peak measurement change from baseline of > 60 ms (adjusted between-arm difference, 0.8%; 95% {CI}, -1.4% to 3.1%; {P} = 0.47). {N}o evidence was found of an association between {C}-max of the antituberculosis drugs 1 month into treatment and the length of {QT}c{F}. {N}either a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of {QT} prolongation in patients with newly diagnosed pulmonary tuberculosis. {T}his is to date the largest data set studying the effects of antituberculosis regimens on the {QT}, both for the standard regimen and for a fluoroquinolone-containing regimen.},
  keywords = {gatifloxacin ; {M}ycobacterium tuberculosis ; {QT} interval ; cardiotoxicity ; fluoroquinolones ; {BENIN} ; {GUINEE} ; {KENYA} ; {SENEGAL} ; {AFRIQUE} {DU} {SUD}},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {61},
  numero = {7},
  pages = {e01834--16 [11 p.]},
  ISSN = {0066-4804},
  year = {2017},
  DOI = {10.1128/aac.01834-16},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070864},
}