Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis

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dc.contributor.authorWallis, Robert S.en_ZA
dc.contributor.authorDawson, Rodneyen_ZA
dc.contributor.authorFriedrich, Sven O.en_ZA
dc.contributor.authorVenter, Amouren_ZA
dc.contributor.authorPaige, Darcyen_ZA
dc.contributor.authorZhu, Tongen_ZA
dc.contributor.authorSilvia, Annetteen_ZA
dc.contributor.authorGobey, Jasonen_ZA
dc.contributor.authorEllery, Craigen_ZA
dc.contributor.authorZhang, Yaoen_ZA
dc.contributor.authorEisenach, Kathleenen_ZA
dc.contributor.authorMiller, Paulen_ZA
dc.contributor.authorDiacon, Andreas H.en_ZA
dc.date.accessioned2016-03-03T09:07:43Z
dc.date.available2016-03-03T09:07:43Z
dc.date.issued2014-04-14
dc.descriptionPlease cite as follows: Wallis, R. S. et al. 2014. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLos ONE, 9(4):e94462, doi:10.1371/journal.pone.0094462.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosoneen_ZA
dc.description.abstractRationale: Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients. Methods: Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv. Results: All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy's criteria for serious liver injury. Conclusions: The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094462
dc.description.versionPublisher's versionen_ZA
dc.format.extent9 pagesen_ZA
dc.identifier.citationWallis, R. S. et al. 2014. Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLos ONE, 9(4):e94462, doi:10.1371/journal.pone.0094462.en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0094462
dc.identifier.urihttp://hdl.handle.net/10019.1/98248
dc.language.isoen_ZAen_ZA
dc.publisherPLoSen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Treatmenten_ZA
dc.subjectTuberculosis -- Immunological aspectsen_ZA
dc.titleMycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosisen_ZA
dc.typeArticleen_ZA
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