Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection.

Adult Antitubercular Agents / administration & dosage Female Humans Linezolid / administration & dosage Male Microbial Sensitivity Tests Mycobacterium tuberculosis / drug effects Prospective Studies South Africa Tuberculosis, Multidrug-Resistant / drug therapy Tuberculosis, Pulmonary / drug therapy
drug-resistant tuberculosis linezolid

Journal

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061

Informations de publication

Date de publication:
03 2019
Historique:
received: 19 10 2018
accepted: 14 12 2018
pubmed: 9 1 2019
medline: 19 2 2020
entrez: 9 1 2019
Statut: epublish

Résumé

The World Health Organization (WHO) recently recommended that linezolid be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in patients with this disease. We conducted an observational study to explore covariate effects on linezolid PK and to estimate the probability of PK/pharmacodynamic target attainment in South African patients with drug-resistant TB. Consecutive adults on linezolid-based regimens were recruited in Cape Town and underwent intensive PK sampling at steady state. Noncompartmental analysis was performed. Thirty participants were included: 15 HIV positive, 26 on the initial dose of 600 mg daily, and 4 participants on 300 mg daily after dose reduction for linezolid-related toxicity. There was a negative correlation between body weight and exposure, with 17.4% (95% confidence interval [CI], 0.1 to 31.7) decrease in area under the concentration-time curve from 0 to 24 h (AUC

Identifiants

DOI: 10.1128/AAC.02164-18 PMID: 30617089 PMC: PMC6395899
pubmed: 30617089
pii: AAC.02164-18
doi: 10.1128/AAC.02164-18
pmc: PMC6395899
pii:
doi:

Substances chimiques

Antitubercular Agents 0
Linezolid ISQ9I6J12J

Types de publication

Journal Article Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
ID : 098316
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203135/Z/16/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111211
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI114444
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114304
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI124414
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States

Informations de copyright

Copyright © 2019 American Society for Microbiology.

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Auteurs

Sean Wasserman (S)

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa sean.wasserman@gmail.com.
ORCID: 0000-0002-3508-6719

Paolo Denti (P)

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
ORCID: 0000-0001-7494-079X

James C M Brust (JCM)

Division of General Internal Medicine, Albert Einstein College of Medicine, New York, New York, USA.
Division of Infectious Diseases, Albert Einstein College of Medicine, New York, New York, USA.

Mahmoud Abdelwahab (M)

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Siphokazi Hlungulu (S)

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Lubbe Wiesner (L)

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
ORCID: 0000-0002-9070-8699

Jennifer Norman (J)

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Frederick A Sirgel (FA)

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.

Robin M Warren (RM)

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research/South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.

Aliasgar Esmail (A)

Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Keertan Dheda (K)

Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Neel R Gandhi (NR)

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Department of Medicine (Infectious Diseases), Emory School of Medicine, Emory University, Atlanta, Georgia, USA.

Graeme Meintjes (G)

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Gary Maartens (G)

Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

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