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- Title
Optimization of linezolid therapy in the critically ill: the effect of adjusted infusion regimens.
- Authors
Taubert, Max; Zander, Johannes; Frechen, Sebastian; Scharf, Christina; Frey, Lorenz; Vogeser, Michael; Fuhr, Uwe; Zoller, Michael
- Abstract
<bold>Objectives: </bold>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.<bold>Methods: </bold>Various infusion regimens (1200-3600 mg/day; q6h, q8h, q12h and continuous) were simulated in 67 000 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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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).
- Subjects
LINEZOLID; OXAZOLIDINONES; INTENSIVE care patients; HEALTH outcome assessment; PHARMACODYNAMICS; ANTIBIOTICS; BLOOD plasma; CATASTROPHIC illness; INTRAVENOUS therapy; MICROBIAL sensitivity tests; GRAM-positive bacterial infections
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2017, Vol 72, Issue 8, p2304
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkx149