Optimization of linezolid therapy in the critically ill: the effect of adjusted infusion regimens.
J Antimicrob Chemother
; 72(8): 2304-2310, 2017 08 01.
Article
em En
| MEDLINE
| ID: mdl-28541510
ABSTRACT
Objectives:
Insufficient linezolid levels, which are associated with a poorer outcome, are often observed in ICU patients who receive standard dosing. Although strategies to overcome these insufficient levels have been discussed, appropriate alternative dosing regimens remain to be identified.Methods:
Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67â¯000 ICU patients. The probability of attaining pharmacodynamic targets ( T >MIC ≥85%, AUC/MIC ≥100, cumulative fraction of response for Staphylococcus aureus and Enterococcus spp., PTA for an MIC of 0.5-4 mg/L) as well as the avoidance of toxic concentrations and concentrations constantly below the MIC (lack of antibiotic effect) or inside a mutant selection window (resistance development) were evaluated.Results:
Best target attainment according to T >MIC was observed for continuous infusions, followed by q6h, q8h and q12h. A substantially reduced target attainment was observed in patients with acute respiratory distress syndrome (ARDS). In patients without ARDS, 1200 mg/day was insufficient irrespective of the regimen, while a dose of 1400 mg/day administered q6h or by continuous infusions provided an acceptable target attainment (e.g. cumulative fraction of response with regards to T >MIC ≥93%). Higher rates of potentially toxic trough concentrations (28% versus 12%) and concentrations constantly inside the mutant selection window (15% versus <0.1%) were observed with continuous infusions compared with q6h infusions (1400 mg/day, patients without ARDS).Conclusions:
Irrespective of the regimen, 1200 mg/day linezolid might be insufficient for the treatment of ICU patients. Patients without ARDS might particularly benefit from q6h infusions with increased daily doses (e.g. 1400 mg/day).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article