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nephrotoxicity. A retrospective cohort study determined nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dL or 50%, was significantly higher in patients on four grams or more per day, with a total body weight of 101.4 kilograms or more, a creatinine clearance of 86.6 mL/min or less, or ICU status.28 Likewise, a recent retrospective cohort study of patients with health-care associated MRSA pneumonia demonstrated that nephrotoxicity is significantly higher with concurrent administration of nephrotoxic drugs, trough concentrations of 15 to 20 mcg/mL and treatment for greater than 8 days.29 Similar to nephrotoxicity, ototoxicity was associated with initial product impurities and is rarely reported in the literature.9, 25 It is somewhat elusive however, since it is more difficult to detect. Baseline and followup audiograms were used to detect high-frequency hearing loss in a case-controlled, retrospective analysis of patients with target vancomycin concentrations of 10 to 20 mcg/mL.30 Of the 89 patients, 11 (12%) experienced high-frequency hearing loss. Independent predictors were abnormal baseline audiograms and age over 53 years. Long-term follow up and correlation of trough vancomycin concentration were not evaluated in the study, but are important considerations. Minimizing toxicity and resistance while improving outcomes is best accomplished by aggressive, empiric dosing based on renal function and actual body weight (table 1), tailoring therapy to MICs and monitoring vancomycin and creatinine concentrations. 13, 31-40 A loading dose of 20 to 25 mg/kg should be considered for critically ill patients in an effort to attain therapeutic concentrations quickly.13,38, 41 Patients with pneumonia, meningitis, endocarditis, organisms with MIC â¥ 1 mcg/mL, sepsis, large volumes of distribution, body mass index â¥ 30 kg/m2, prolonged therapy, renal insufficiency and dialysis require monitoring of trough concentrations to ensure adequate concentrations throughout the dosing interval and minimize toxicity.13 Table 1. Adult vancomycin dosing nomogram A d u lt Va nc o m yc i n D o s in g N o mo gr a m 3 8 , 4 0 Creatinine Clearance* â¥100 mL/min 80 - 99 mL/min 56 - 79 mL/min 40 - 55 mL/min 30 - 39 mL/min 20 - 29 mL/min <20 mL/min Initial Dose (ABW)â 15 - 25 mg/kg 15 - 25 mg/kg 15 - 25 mg/kg 15 - 25 mg/kg 15 - 25 mg/kg 15 - 25 mg/kg 15 - 20 mg/kg Hemodialysis 15 â 20 mg/kg or 1 g CRRT 15 â 20 mg/kg Maintenance Dose(ABW)â 10 mg/kg Q 8 h 15 mg/kg Q 12 h 10 mg/kg Q 12 h 15 mg/kg Q 24h 10 mg/kg Q 24 h 15 mg/kg Q 48 h Monitor serum concentrations 500 - 750 mg after dialysis or monitor serum concentration as indicated in sections 7 below 1 g Q 12 â 24 h Monitor serum concentrations ABW â actual body weight, CRRT â continuous renal replacement therapy * Dosing recommendations are based on decreasing creatinine clearance, which can be measured directly or estimated with equations such as the Cockcroft-Gault equation. In obese patients with a BMI > 2 42 30 kg/m , the Salazaar-Corcoran equation is more precise and less biased. For more information; please consult the protocol for renal-based dose adjustments. Renal Function-Based Dose Adjustment in Adults â Round doses down to the nearest 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g dose. If higher single doses are calculated, then consider giving a smaller dose more frequently. Maximum infusion rate is 10 mg/min or over 1 hour, whichever is longer. Minimum dilution is 5 mg/mL in a peripheral line.