International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Apr 2012
Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients.
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. ⋯ 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.
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Int. J. Antimicrob. Agents · Apr 2012
Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury.
Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.