title: Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients.
abstract: Vancomycin is frequently administered to critically ill patients by continuous infusion in order to optimise drug efficacy; however, there are few data available on the efficacy of this strategy in septic patients. In this retrospective analysis, 261 patients treated with continuous infusion of vancomycin in the Department of Intensive Care at Hôpital Erasme (Brussels, Belgium) were evaluated. Creatinine clearance (CL(Cr)) was calculated from 24-h urine collection and normalised to body surface area. During the study period, 139 patients (53%) had insufficient vancomycin concentrations (<20 μg/mL) on Day 1 and 87 patients (33%) on Day 2. Patients who had insufficient drug concentrations on Day 1 of therapy were more likely to be men, to have a higher CL(Cr) and to have received lower loading and daily vancomycin doses than other patients, who received greater vasopressor support and had higher Sepsis-related Organ Failure Assessment scores. In multivariate regression analysis, high CL(Cr) and male sex independently predicted the presence of insufficient vancomycin concentrations on Days 1 and 2 of therapy. Receiver operating characteristic curve analysis for CL(Cr) showed an area under the concentration-time curve of 0.75 (95% confidence interval 0.69-0.81) to predict insufficient drug concentrations on Day 1 of therapy. A CL(Cr)>120 mL/min/1.73 m(2) had a sensitivity of 26%, a specificity of 94% and an 84% positive predictive value of 84% for vancomycin concentrations <20 μg/mL. In conclusion, approximately one-half of the septic Intensive Care Unit patients treated with continuous infusion of vancomycin at currently recommended doses had insufficient drug concentrations in the early phase of therapy. A high CL(Cr) was the variable most strongly associated with insufficient drug concentrations.
authors.affiliation: Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Ocampos-Martinez
authors.forename: Laura
authors.initials: L
authors.lastname: Penaccini
authors.forename: Sabino
authors.initials: S
authors.lastname: Scolletta
authors.forename: Ali
authors.initials: A
authors.lastname: Abdelhadii
authors.forename: Alessandro
authors.initials: A
authors.lastname: Devigili
authors.forename: Silvia
authors.initials: S
authors.lastname: Cianferoni
authors.forename: Daniel
authors.initials: D
authors.lastname: de Backer
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cotton
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D012720:Severity of Illness Index; D013997:Time Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000592:standards / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine