Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.
J Antimicrob Chemother
; 78(12): 2840-2848, 2023 12 01.
Article
en En
| MEDLINE
| ID: mdl-37823408
ABSTRACT
BACKGROUND:
Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.OBJECTIVES:
Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS ANDMETHODS:
Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.RESULTS:
We demonstrated a substantial increase of linezolid clearance by 150% (95% CI 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2â mg/L and 4â mg/L, respectively.CONCLUSIONS:
A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rifampin
/
Endocarditis Bacteriana
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article