Performance of a Vancomycin Dosage Regimen Developed for Obese Patients

David C. Reynolds, Pharm.D; Laura H. Waite, Pharm.D; Donald P. Alexander, Pharm.D; C. Andrew DeRyke, Pharm.D

Disclosures

Am J Health Syst Pharm. 2012;69(11):944-950. 

In This Article

Abstract and Introduction

Abstract

Purpose An original and a revised vancomycin dosing protocol for obese patients were compared with respect to attainment of target serum trough vancomycin concentrations and the occurrence of nephrotoxicity.
Methods The attainment of target vancomycin trough values (10–20 μg/mL) and nephrotoxicity were compared retrospectively between an original protocol (vancomycin 15 mg/kg i.v. every 8–12 hours), which had been associated with high troughs, and a revised protocol (10 mg/kg i.v. every 12 hours or 15 mg/kg every 24 hours). Patients were included if they were obese (weight ≥ 100 kg and total body weight ≥ 140% of ideal body weight), had normal renal function (creatinine clearance ≥ 60 mL/min), had received i.v. vancomycin for at least 48 hours, and had one evaluable vancomycin trough value. Nephrotoxicity was defined as an increase in serum creatinine concentration of 0.5 mg/dL or of 50% over baseline, whichever was greater.
Results Seventy-four and 64 patients were stratified into groups that had been treated with the revised and original protocols, respectively. The mean ± S.D. maintenance dose was 19 ± 2 mg/kg/day with the revised protocol and 34 ± 7 mg/kg/day with the original protocol (p < 0.001). Compared with the original protocol, the revised protocol resulted in a higher frequency of target troughs (59% versus 36%, p = 0.006) and below-target troughs (23% versus 9%, p = 0.033) and a lower frequency of above-target troughs (18% versus 55%, p < 0.001). Nephrotoxicity occurred in two patients in each group.
Conclusion Compared with the original vancomycin protocol for obese patients, a revised vancomycin protocol using lower total daily doses improved the attainment of target trough concentrations, with minimal nephrotoxicity.

Introduction

Within our institution, vancomycin is generally considered the first-line therapy for most infections caused by gram-positive organisms. Despite extensive experience with vancomycin, achieving a desired trough concentration with empiric dosing remains a significant clinical challenge. In 2009, the American Society of Health-System Pharmacists (ASHP), Infectious Diseases Society of America (IDSA), and Society of Infectious Diseases Pharmacists (SIDP) endorsed a consensus statement on the dosing and monitoring of vancomycin.[1] This consensus statement recommends vancomycin maintenance dosing of 15–20 mg/kg i.v. every 8–12 hours for most patients with normal renal function. At the time the document was published, our institution was using a dosing protocol largely consistent with those recommendations.

Unfortunately, as noted in the consensus statement, limited data are available to guide empirical vancomycin dosing in obese patients. Published pharmacokinetic data indicate accelerated renal clearance (CL) of vancomycin in obese patients, which would appear to justify a weight-based dosing regimen, with doses increasing as a function of body weight.[2–5] However, on using weight-based vancomycin regimens in obese patients in routine clinical practice, we observed trough serum vancomycin concentrations of >20 μg/mL in approximately 50% of patients. As vancomycin dosing in our institution is managed by a pharmacist for the majority of patients, frequent higher-than-desired trough vancomycin concentrations in obese patients and the need for subsequent measurement of vancomycin levels led to increased pharmacy resource utilization and decreased physician confidence in pharmacist-managed therapy. Of note, despite the repeated attainment of trough vancomycin concentrations of >20 μg/mL, nephrotoxicity was rarely observed.

In response to the high vancomycin trough values commonly obtained from obese patients at our institution, modeling was performed to devise empirical dosing recommendations that more consistently resulted in steady-state trough vancomycin concentrations of 10–20 μg/mL, as well as a value of ≥400 for the quotient of the 24-hour area under the serum concentration–time curve (AUC) divided by the minimum inhibitory concentration (MIC), or AUC/MIC, when the MIC is =1 μg/mL.[6] A detailed description of this method has been published.[7] After performing this exercise on approximately 50 hospitalized obese patients receiving vancomycin, the Orlando Health vancomycin dosing protocol was subsequently revised with the recommendation to treat obese adult patients who have normal renal function with a loading dose of 20–25 mg/kg i.v. followed by maintenance dosing of 10 mg/kg i.v. every 12 hours or 15 mg/kg every 24 hours. The purpose of the project described here was to compare the performance of the original and revised protocols, as well as the associated nephrotoxicity rates.

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