Open AccessProspectively Validated Dosing Nomograms for Maximizing the Pharmacodynamics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients
Author(s) -
Federico Pea,
Mario Furlanut,
Camilla Negri,
Federica Pavan,
Massimo Crapis,
Francesco Cristini,
Pierluigi Viale
Publication year - 2009
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01149-08
Subject(s) - dosing , vancomycin , liter , nomogram , pharmacodynamics , medicine , loading dose , staphylococcus aureus , pharmacokinetics , critically ill , creatinine , therapeutic drug monitoring , antibacterial agent , antibiotics , anesthesia , microbiology and biotechnology , biology , bacteria , genetics
The efficacy of vancomycin against methicillin-resistantStaphylococcus aureus (MRSA)-related infections has been called into question by recent findings of higher rates of failure of vancomycin treatment of infections caused by strains with high MICs. Continuous infusion may be the best way to maximize the time-dependent activity of vancomycin. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CLCr ) estimates for use in daily clinical practice to target the steady-state concentrations (C ss s) of vancomycin during continuous infusion at 15 to 20 mg/liter (after the administration of an initial loading dose of 15 mg/kg of body weight over 2 h). The correlation between vancomycin clearance (CLv ) and CLCr was retrospectively assessed in a cohort of critically ill patients (group 1,n = 70) to create a formula for dosage calculation to targetC ss at 15 mg/liter. The performance of this formula was prospectively validated in a similar cohort (group 2,n = 63) by comparison of the observed and the predictedC ss s. A significant relationship between CLv and CLCr was observed in group 1 (P < 0.001). The application of the calculated formula to vancomycin dosing in group 2 {infusion rate (g/24 h) = [0.029 × CLCr (ml/min) + 0.94] × target Css × (24/1,000)} led to a significant correlation between the observed and the predictedC ss s (r = 0.80,P < 0.001). Two dosing nomograms based on CLCr were created to target the vancomycinC ss at 15 and 20 mg/liter in critically ill patients. These nomograms could be helpful in improving the vancomycin treatment of MRSA infections, especially in the presence of borderline-susceptible pathogens and/or of pathophysiological conditions which may enhance the clearance of vancomycin, while potentially avoiding the increased risk of nephrotoxicity observed with the use of high intermittent doses of vancomycin.