title: Risk factors for a low linezolid trough plasma concentration in acute infections.
abstract: Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (C(min)) and to determine factors associated with a C(min) < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a C(min) determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low C(min). A total of 29.5% of patients had a C(min) < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of C(min) < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid C(min) of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.
authors: Department of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain.
authors: Laura
authors: L
authors: Morata
authors: Marta
authors: M
authors: Cuesta
authors: Jhon F
authors: JF
authors: Rojas
authors: Sebastian
authors: S
authors: Rodriguez
authors: Merce
authors: M
authors: Brunet
authors: Gregori
authors: G
authors: Casals
authors: Nazareth
authors: N
authors: Cobos
authors: Cristina
authors: C
authors: Hernandez
authors: José A
authors: JA
authors: Martínez
authors: Josep
authors: J
authors: Mensa
authors: Alex
authors: A
authors: Soriano
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D012307:Risk Factors; D013203:Staphylococcal Infections / Q000097:blood / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid
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