International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · May 2012
Augmented renal clearance in septic patients and implications for vancomycin optimisation.
The aim of this study was to evaluate the effect of augmented renal clearance (ARC) on vancomycin serum concentrations in critically ill patients. This prospective, single-centre, observational, cohort study included 93 consecutive, critically ill septic patients who started treatment that included vancomycin by continuous infusion, admitted over a 2-year period (March 2006 to February 2008). ARC was defined as 24-h creatinine clearance (CL(Cr))>130 mL/min/1.73 m(2). ⋯ Serum vancomycin levels on D(1), D(2) and D(3), respectively, were 13.1, 16.6 and 18.6 μmol/L for Group A and 9.7, 11.7 and 13.8 μmol/L for Group B (P<0.05 per day). The correlation between CL(Cr) and serum vancomycin on D(1) was -0.57 (P<0.001). ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment.
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Int. J. Antimicrob. Agents · May 2012
Outpatient parenteral antimicrobial therapy (OPAT) in a teaching hospital-based practice: a retrospective cohort study describing experience and evolution over 10 years.
Use of outpatient parenteral antimicrobial therapy (OPAT) is increasing in settings with advanced healthcare systems internationally. This study describes a large OPAT service cohort developed in the west of Scotland and includes trends over a 10-year period of this service. Data were retrieved from a prospectively maintained electronic case database. ⋯ Outcome proportions (success and adverse events) did not vary over time. This cohort study adds to the increasing observational data suggesting that OPAT is safe, effective and acceptable for treating a wide variety of infections. Observed trends over a 10-year period suggest that this model of infection management is adaptable and sustainable.
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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.
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Int. J. Antimicrob. Agents · Mar 2012
ReviewHow to optimise antimicrobial prescriptions in the Intensive Care Unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics.
Optimising antimicrobial dosing for critically ill patients is highly challenging and when it is not achieved can lead to worse patient outcomes. To this end, use of dosing regimens recommended in package inserts from drug manufacturers is frequently insufficient to guide dosing in these patients appropriately. Whilst the effect of critical illness pathophysiology on the pharmacokinetic (PK) behaviour of antimicrobials can be profound, the variability of these changes between patients is still being quantified. ⋯ This paper outlines the factors that affect pharmacokinetics in critically ill patients and how knowledge of these factors can increase the likelihood of achieving optimal antimicrobial plasma concentrations. In selected settings, we advocate individualised dosing of renally cleared antimicrobials using physiological data such as measured creatinine clearance and published non-renal clearance data. Where such data do not exist, therapeutic drug monitoring may be a useful alternative and has been associated with significant clinical benefits, although it is not currently widely available.