title: Implementation of a protocol for administration of vancomycin by continuous infusion: pharmacokinetic, pharmacodynamic and toxicological aspects.
abstract: Optimising antibiotic administration is critical when dealing with pathogens with reduced susceptibility. Vancomycin activity is dependent on the area under the concentration-time curve over 24 h at steady-state divided by the minimum inhibitory concentration (AUC/MIC), making continuous infusion (CI) or conventional twice daily administration pharmacodynamically equipotent. Because CI facilitates drug administration and serum level monitoring, we have implemented a protocol for CI of vancomycin by: (i) examining whether maintaining stable serum concentrations (set at 25-30 mg/L based on local susceptibility data of Gram-positive target organisms) can be achieved in patients suffering from difficult-to-treat infections; (ii) assessing toxicity (n = 94) and overall efficacy (n = 59); and (iii) examining the correlation between AUC/MIC and the clinical outcome in patients for whom vancomycin was the only active agent against a single causative pathogen (n = 20). Stable serum levels at the expected target were obtained at the population level (loading dose 20mg/kg; infusion of 2.57 g/24 h adjusted for creatinine clearance) for up to 44 days, but large intrapatient variations required frequent dose re-adjustments (increase in 57% and decrease in 16% of the total population). Recursive partitioning analysis of AUC/MIC ratios versus success or failure suggested threshold values of 667 (total serum level) and 451 (free serum level), corresponding to organisms with a MIC>1 mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10% of patients, but treatment had to be discontinued in only two of them.
authors.affiliation: Pharmacologie cellulaire et moléculaire et Centre de pharmacie clinique, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Ampe
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Delaere
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Hecq
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.forename: Youri
authors.initials: Y
authors.lastname: Glupczynski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin