216. High Loading Doses of Vancomycin (≥ 25 mg/kg) are Associated with an Increased Incidence of Nephrotoxicity
Session: Poster Abstract Session: Antimicrobial Resistance: Clinical Studies
Friday, October 21, 2011
Room: Poster Hall B1
Background: Current guidelines for vancomycin therapeutic monitoring state loading doses of 25 – 30 mg/kg can be considered for seriously ill patients.  Concerns regarding adverse events associated with larger doses of vancomycin prompted investigation into the incidence of nephrotoxicity in patients who received high loading doses of vancomycin (≥ 25 mg/kg) compared to those who received conventional loading doses (15 – 24 mg/kg).  

Methods: All adults ≥ 18 years-old who received a loading dose of vancomycin ≥ 15 mg/kg between October 29, 2007 and May 31, 2010 were retrospectively identified.  Patients who were pregnant, hemodialysis-dependent, or had insufficient data for analysis were excluded.  Nephrotoxicity, defined as a > 50% increase in serum creatinine or a urine output < 0.5 mL/kg/hr over 6 hours, was the primary endpoint.  Follow-up was limited to the first 48 hours after vancomycin loading dose administration. 

Results: A total of 1,441 patients met entry criteria with 413 in the high loading dose arm and 1,028 in the conventional dose cohort.  Those in the high loading dose group tended to be younger (57.3 ± 19.2 years vs 60.3 ± 18.3 years; p = 0.006), more likely to be in an intensive care unit (73.8% vs 47.2%; p < 0.001), or septic (51.6% vs 34.6%; p < 0.001).  Incidence of nephrotoxicity was 22.5% in the high loading dose group compared to 16.5% in the conventional dose group (p = 0.01).   Increases in serum creatinine were similar between both groups (high loading dose 6.5%, conventional dose 6.1%; p = 0.90).  Decreased urine output was significantly more pronounced in the high loading dose group compared to the conventional dose cohort (19.8% vs 14.2%; p = 0.012). Administration of high vancomycin loading doses (OR = 1.38; 95% CI, 1.02 – 1.85), patient weight (OR = 1.01; 95% CI, 1.01 – 1.02), heart failure (OR = 1.85; 95% CI, 1.38 – 2.49), and sepsis (OR = 1.67; 95% CI, 1.26 – 2.20) were identified as independent risk factors for nephrotoxicity. 

Conclusion: Administration of high loading doses of vancomycin contributes to an increased incidence of new-onset nephrotoxicity within the first 48 hours of administration.  Patient weight, heart failure, and sepsis were also identified as predictive risk factors for nephrotoxicity.

Subject Category: A. Antimicrobial agents and Resistance

David K. Hwang, PharmD, PhD, Travis B. Dick, PharmD, BCPS, Paul Wohlt, PharmD, BCPS and Elizabeth Sebranek-Evans, PharmD, BCPS, CGP, Intermountain Medical Center, Murray, UT


D. K. Hwang, None

T. B. Dick, None

P. Wohlt, None

E. Sebranek-Evans, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.