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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis
PLoS ONE, Volume 9, No. 4, Article e94462, Year 2014
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Description
Rationale: 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. © 2014 Wallis et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3986205/bin/pone.0094462.s001.docx
https://efashare.b-cdn.net/share/pmc/articles/PMC3986205/bin/pone.0094462.s002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3986205/bin/pone.0094462.s003.pdf
Authors & Co-Authors
Wallis, Robert S.
United States, New York
Pfizer Inc.
South Africa, Johannesburg
The Aurum Institute
Dawson, Rodney
South Africa, Cape Town
University of Cape Town
Friedrich, Sven Olaf
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Venter, Amour
South Africa, Stellenbosch
Stellenbosch University
Paige, Darcy
United States, New York
Pfizer Inc.
Zhu, Tong
United States, New York
Pfizer Inc.
Silvia, Annette
United States, New York
Pfizer Inc.
Gobey, Jason
United States, New York
Pfizer Inc.
Ellery, Craig
United States, New York
Pfizer Inc.
Zhang, Yao
United States, New York
Pfizer Inc.
Eisenach, Kathleen D.
United States, Little Rock
University of Arkansas for Medical Sciences
Miller, Paul
United States, New York
Pfizer Inc.
United Kingdom, Cambridge
Astrazeneca
Diacon, Andreas Henri
South Africa, Cape Town
Stellenbosch University, Faculty of Medicine and Health Sciences
Statistics
Citations: 131
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0094462
e-ISSN:
19326203
Research Areas
Infectious Diseases
Maternal And Child Health
Violence And Injury