An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens : study protocol for a randomized controlled trial

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dc.contributor.authorBouton, Tara C.en_ZA
dc.contributor.authorPhillips, Patrick P. J.en_ZA
dc.contributor.authorMitnick, Carole D.en_ZA
dc.contributor.authorPeloquin, Charles A.en_ZA
dc.contributor.authorEisenach, Kathleenen_ZA
dc.contributor.authorPatientia, Ramonde F.en_ZA
dc.contributor.authorLecca, Leoniden_ZA
dc.contributor.authorGotuzzo, Eduardoen_ZA
dc.contributor.authorGandhi, Neel R.en_ZA
dc.contributor.authorButler, Donnaen_ZA
dc.contributor.authorDiacon, Andreas H.en_ZA
dc.contributor.authorMartel, Brunoen_ZA
dc.contributor.authorSantillan, Juanen_ZA
dc.contributor.authorHunt, Kathleen R.en_ZA
dc.contributor.authorVargas, Danteen_ZA
dc.contributor.authorVon Groote-Bidlingmaier, Florianen_ZA
dc.contributor.authorSeas, Carlosen_ZA
dc.contributor.authorDianis, Nancyen_ZA
dc.contributor.authorMoreno-Martinez, Antonioen_ZA
dc.contributor.authorHorsburgh, C. R.en_ZA
dc.date.accessioned2017-11-27T06:04:00Z
dc.date.available2017-11-27T06:04:00Z
dc.date.issued2017-11-25
dc.date.updated2017-11-26T04:57:58Z
dc.descriptionCITATION: Bouton, T. C., et al. 2017. An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens : study protocol for a randomized. Trials, 18:563, doi:10.1186/s13063-017-2292-x.
dc.descriptionThe original publication is available at https://trialsjournal.biomedcentral.com
dc.description.abstractBackground: Current guidelines for treatment of multidrug-resistant tuberculosis (MDR-TB) are largely based on expert opinion and observational data. Fluoroquinolones remain an essential part of MDR-TB treatment, but the optimal dose of fluoroquinolones as part of the regimen has not been defined. Methods/design: We designed a randomized, blinded, phase II trial in MDR-TB patients comparing across levofloxacin doses of 11, 14, 17 and 20 mg/kg/day, all within an optimized background regimen. We assess pharmacokinetics, efficacy, safety and tolerability of regimens containing each of these doses. The primary efficacy outcome is time to culture conversion over the first 6 months of treatment. The study aims to determine the area under the curve (AUC) of the levofloxacin serum concentration in the 24 hours after dosing divided by the minimal inhibitory concentration of the patient’s Mycobacterium tuberculosis isolate that inhibits > 90% of organisms (AUC/MIC) that maximizes efficacy and the AUC that maximizes safety and tolerability in the context of an MDR-TB treatment regimen. Discussion: Fluoroquinolones are an integral part of recommended MDR-TB regimens. Little is known about how to optimize dosing for efficacy while maintaining acceptable toxicity. This study will provide evidence to support revised dosing guidelines for the use of levofloxacin as part of combination regimens for treatment of MDR-TB. The novel methodology can be adapted to elucidate the effect of other single agents in multidrug antibiotic treatment regimens.
dc.description.urihttps://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2292-x
dc.description.versionPublisher's version
dc.format.extent8 pages : illustrationsen_ZA
dc.identifier.citationBouton, T. C., et al. 2017. An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens : study protocol for a randomized. Trials, 18:563, doi:10.1186/s13063-017-2292-x
dc.identifier.issn1745-6215 (online)
dc.identifier.otherdoi:10.1186/s13063-017-2292-x
dc.identifier.urihttp://hdl.handle.net/10019.1/102511
dc.language.isoen_ZAen_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMultidrug-resistant tuberculosisen_ZA
dc.subjectFluoroquinolonesen_ZA
dc.subjectTuberculosis -- Chemotherapyen_ZA
dc.subjectClinical drug trialsen_ZA
dc.titleAn optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens : study protocol for a randomized controlled trialen_ZA
dc.typeArticleen_ZA
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