Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study
1 Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Dallas, USA
2 Department of Clinical Sciences, University of Texas Southwestern, Dallas, USA
3 Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, USA
4 Division of Pharmacotherapy, University of Texas, Austin, USA
5 Department of Internal Medicine, Texas Tech University Health Sciences Center, School of Medicine, Amarillo, USA
6 Department of Internal Medicine, University of Texas Southwestern, Dallas, USA
7 Current affiliation: University of Wyoming School of Pharmacy, Swedish Family Medicine Residency Program, Englewood, USA
8 Current affiliation: University of Kentucky Healthcare, Lexington, USA
9 Current affiliation: Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, USA
10 Current affiliation: Mission Regional Medical Center, Mission, USA
BMC Pharmacology and Toxicology 2013, 14:12 doi:10.1186/2050-6511-14-12Published: 13 February 2013
Previous studies have established a correlation between vancomycin troughs and nephrotoxicity. However, data are currently lacking regarding the effect of guideline-recommended weight-based dosing on nephrotoxicity in methicillin-resistant Staphylococcus aureus bacteremia (MRSAB).
Adults who were at least 18 years of age with methicillin-resistant Staphylococcus aureus bacteremia and received of empiric vancomycin therapy for at least 48 hours (01/07/2002 and 30/06/2008) were included in this multicenter, retrospective cohort study. The association between guideline-recommended, weight-based vancomycin dosing (at least 15 mg/kg/dose) and nephrotoxicity (increase in serum creatinine (SCr) by more than 0.5 mg/dl or at least a 50% increase from baseline on at least two consecutive laboratory tests) was evaluated. Potential independent associations were evaluated using a multivariable general linear mixed-effect model.
Overall, 23% of patients developed nephrotoxicity. Thirty-four percent of the 337 patients who met study criteria received weight-based dosing. The cohort was composed of 69% males with a median age of 55 years. The most common sources of MRSAB included skin/soft tissue (32%), catheter-related bloodstream bacteremia (20%), pulmonary (18%). Eighty-six percent of patients received twice daily dosing. Similar rates of nephrotoxicity were observed regardless of the receipt of guideline-recommended dosing (22% vs. 24%, OR 0.91 [95% CI 0.53-1.56]). This finding was confirmed in the multivariable analysis (OR 1.52 [95% CI 0.75-3.08]). Independent predictors of nephrotoxicity were (OR, 95% CI) vancomycin duration of greater than 15 days (3.36, 1.79-6.34), weight over 100 kg (2.74, 1.27-5.91), Pitt bacteremia score of 4 or greater (2.73, 1.29-5.79), vancomycin trough higher than 20 mcg/ml (2.36, 1.07-5.20), and age over 52 years (2.10, 1.08-4.08).
Over one out of five patients in this study developed nephrotoxicity while receiving vancomycin for MRSAB. The receipt of guideline-recommended, weight-based vancomycin was not an independent risk factor for the development of nephrotoxicity.