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Antimicrobial Agents and Chemotherapy, May 2009, p. 1863-1867, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01149-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Prospectively Validated Dosing Nomograms for Maximizing the Pharmacodynamics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients
Federico Pea,1*
Mario Furlanut,1
Camilla Negri,2
Federica Pavan,1
Massimo Crapis,2
Francesco Cristini,2 and
Pierluigi Viale2
Institute of Clinical Pharmacology & Toxicology, Department of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy,1 Clinic of Infectious Diseases, Department of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy2
Received 27 August 2008/ Returned for modification 25 November 2008/ Accepted 28 January 2009
The efficacy of vancomycin against methicillin-resistant Staphylococcus 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 (Csss) 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 target Css 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 predicted Csss. 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 x CLCr (ml/min) + 0.94] x target Css x (24/1,000)} led to a significant correlation between the observed and the predicted Csss (r = 0.80, P < 0.001). Two dosing nomograms based on CLCr were created to target the vancomycin Css 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.
* Corresponding author. Mailing address: Institute of Clinical Pharmacology & Toxicology, DPMSC, University of Udine, P. le S. Maria della Misericordia 3, 33100 Udine, Italy. Phone: 39 0432 559833. Fax: 39 0432 559819. E-mail: pea.federico{at}aoud.sanita.fvg.it
Published ahead of print on 17 February 2009.
Antimicrobial Agents and Chemotherapy, May 2009, p. 1863-1867, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01149-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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