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Antimicrobial Agents and Chemotherapy, April 2008, p. 1330-1336, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01602-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Larger Vancomycin Doses (at Least Four Grams per Day) Are Associated with an Increased Incidence of Nephrotoxicity{triangledown}

Thomas P. Lodise,1,2* Ben Lomaestro,3 Jeffrey Graves,1 and G. L. Drusano2

Albany College of Pharmacy, Albany, New York,1 Ordway Research Institute, Albany, New York,2 Albany Medical Center Hospital, Albany, New York3

Received 12 December 2007/ Returned for modification 8 January 2008/ Accepted 22 January 2008

Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to ≥4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses. The purpose of this study was to examine vancomycin-associated nephrotoxicity at ≥4 g/day. To accomplish the study objective, a cohort study among a random selection of patients receiving vancomycin or linezolid between 2005 and 2006 was performed. Patients were included if they (i) were ≥18 years of age, (ii) were nonneutropenic, (iii) were on therapy for >48 h, (iv) had baseline serum creatinine levels of <2.0 mg/dl, (v) did not suffer from cystic fibrosis, and (vi) had no intravenous contrast dye within the previous 7 days. For drug exposure, three treatment strata were created: standard vancomycin dose (<4 g/day), high vancomycin dose (≥4 g/day), and linezolid. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/dl or 50%, whichever was greater, after therapy initiation. Stratified Kaplan-Meier analysis and Cox modeling were used to compare times to nephrotoxicity across groups. During the study, 246 patients on vancomycin (26 patients taking ≥4 g/day and 220 patients taking <4 g/day) and 45 patients on linezolid met the criteria. A significant difference in nephrotoxicity between patients receiving ≥4 g vancomycin/day, those receiving <4 g vancomycin/day, and those receiving linezolid was noted (34.6%, 10.9%, and 6.7%, respectively; P = 0.001), and Kaplan-Meier analysis identified significant differences in time to nephrotoxicity for the high-vancomycin-dose cohort compared to those for groups taking the standard dose and linezolid. In the Cox model, patients taking ≥4 g vancomycin/day, a total body weight of ≥101.4 kg, estimated creatinine clearance of ≤86.6 ml/min, and intensive care unit residence were independently associated with time to nephrotoxicity. The data suggest that higher-dose vancomycin regimens are associated with a higher likelihood of vancomycin-related nephrotoxicity.

* Corresponding author. Mailing address: Department of Pharmacy Practice, Albany College of Pharmacy, Albany, NY 12208. Phone: (518) 445-7200, ext. 292. Fax: (518) 694-7062. E-mail: Lodiset{at}acp.edu

{triangledown} Published ahead of print on 28 January 2008.

Antimicrobial Agents and Chemotherapy, April 2008, p. 1330-1336, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.01602-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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