Longitudinal Pharmacokinetic-Pharmacodynamic Biomarkers Correlate With Treatment Outcome in Drug-Sensitive Pulmonary Tuberculosis: A Population Pharmacokinetic-Pharmacodynamic Analysis.
outcome
pharmacodynamics
pharmacokinetics
standard treatment
tuberculosis
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
03
03
2020
accepted:
03
06
2020
entrez:
1
8
2020
pubmed:
1
8
2020
medline:
1
8
2020
Statut:
epublish
Résumé
This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions. Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM. Outcome data were analyzed using univariate logistic regression and Cox proportional hazard models in R, a free software for statistical computing. Higher isoniazid exposure correlated with increased bacillary killing in sputum ( Patterns of early bacillary clearance matter. Static measurements such as month 2 sputum conversion and pharmacokinetic parameters such as
Sections du résumé
BACKGROUND
BACKGROUND
This study aims to explore relationships between baseline demographic covariates, plasma antibiotic exposure, sputum bacillary load, and clinical outcome data to help improve future tuberculosis (TB) treatment response predictions.
METHODS
METHODS
Data were available from a longitudinal cohort study in Malawian drug-sensitive TB patients on standard therapy, including steady-state plasma antibiotic exposure (154 patients), sputum bacillary load (102 patients), final outcome (95 patients), and clinical details. Population pharmacokinetic and pharmacokinetic-pharmacodynamic models were developed in the software package NONMEM. Outcome data were analyzed using univariate logistic regression and Cox proportional hazard models in R, a free software for statistical computing.
RESULTS
RESULTS
Higher isoniazid exposure correlated with increased bacillary killing in sputum (
CONCLUSIONS
CONCLUSIONS
Patterns of early bacillary clearance matter. Static measurements such as month 2 sputum conversion and pharmacokinetic parameters such as
Identifiants
pubmed: 32733976
doi: 10.1093/ofid/ofaa218
pii: ofaa218
pmc: PMC7378673
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofaa218Subventions
Organisme : Medical Research Council
ID : MC_PC_16052
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P014534/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P020526/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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