Linezolid Pharmacokinetic-Anemia Modeling in Children With Rifampicin-Resistant Tuberculosis

Linezolid, a component of rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR/MDR-T...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Clinical infectious diseases Jg. 79; H. 6; S. 1495
Hauptverfasser: Brooks, Jordan T, Solans, Belén P, Béranger, Agathe, Schaaf, H Simon, van der Laan, Louvina, Sharma, Sangeeta, Furin, Jennifer, Draper, Heather R, Hesseling, Anneke C, Garcia-Prats, Anthony J, Savic, Radojka M
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 17.12.2024
Schlagworte:
Adolescent
Anemia
Antitubercular Agents - adverse effects
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - therapeutic use
Child
Child, Preschool
Female
Humans
India - epidemiology
Linezolid - administration & dosage
Linezolid - adverse effects
Linezolid - pharmacokinetics
Linezolid - therapeutic use
Male
Prospective Studies
Rifampin - pharmacokinetics
Rifampin - therapeutic use
Risk Factors
South Africa
Tuberculosis, Multidrug-Resistant - drug therapy
South Africa
India
pharmacokinetics
linezolid
dosing
children
anemia
ISSN:1537-6591, 1537-6591
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Linezolid, a component of rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR/MDR-TB. We evaluated the pharmacokinetics of linezolid and longitudinal hemoglobin data to validate an existing population linezolid pharmacokinetic model. We assessed the impact of linezolid pharmacokinetics and the risk of developing anemia in a prospectively enrolled cohort of children. A previously published population pharmacokinetic linezolid model was validated using nonlinear mixed effects modeling. A multivariable ordinal logistic regression model was built to predict the incidence of anemia. A total of 112 children, median age 7.2 years (interquartile range, 2.2-16.3), were included from South Africa (n = 87) and India (n = 25). Of these, 24 children contributed new linezolid pharmacokinetic data. The population pharmacokinetic model, which informs the currently recommended linezolid dosing in children (10-15 mg/kg), was validated with these additional new data. For every 1 g/dL lower baseline hemoglobin level, the odds of developing grade 3 or 4 anemia increased by 2.64 (95% confidence interval [CI], 1.98-3.62). For every 1 mg/L × h higher linezolid area under the concentration-time curve, the odds of developing grade 3 or 4 anemia increased by 1.012 (95% CI, 1.007-1.017). Taken together, these data confirm currently recommended linezolid doses for children. The risk of anemia in children should be carefully considered and monitored. Initiating linezolid in children with low baseline hemoglobin increases the probability of experiencing grade 3 or 4 anemia.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1537-6591
1537-6591
DOI:10.1093/cid/ciae497