title: Empiric guideline-recommended weight-based vancomycin dosing and nephrotoxicity rates in patients with methicillin-resistant Staphylococcus aureus bacteremia: a retrospective cohort study.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacy Practice, Texas Tech University Health Sciences Center, School of Pharmacy, Dallas, TX, USA. ronald.hall@ttuhsc.edu
authors: Ronald G
authors: RG
authors: Hall
authors: Kathleen A
authors: KA
authors: Hazlewood
authors: Sara D
authors: SD
authors: Brouse
authors: Christopher A
authors: CA
authors: Giuliano
authors: Krystal K
authors: KK
authors: Haase
authors: Chistopher R
authors: CR
authors: Frei
authors: Nicolas A
authors: NA
authors: Forcade
authors: Todd
authors: T
authors: Bell
authors: Roger J
authors: RJ
authors: Bedimo
authors: Carlos A
authors: CA
authors: Alvarez
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016470:Bacteremia / Q000188:drug therapy*; D001835:Body Weight; D005260:Female; D006761:Hospitals; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D013203:Staphylococcal Infections / Q000188:drug therapy*; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
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