Antimicrobial Use Guidelines (AMUG) version 21 - UW Health

nephrotoxicity. A retrospective cohort study determined nephrotoxicity, defined as an increase in serumcreatinine of 0.5 mg/dL or 50%, was significantly higher in patients on four grams or more per day, with atotal body weight of 101.4 kilograms or more, a creatinine clearance of 86.6 mL/min or less, or ICUstatus. 28 Likewise, a recent retrospective cohort study of patients with health-care associated MRSApneumonia demonstrated that nephrotoxicity is significantly higher with concurrent administration ofnephrotoxic drugs, trough concentrations of 15 to 20 mcg/mL and treatment for greater than 8 days. 29Similar to nephrotoxicity, ototoxicity was associated with initial product impurities and is rarely reported in9, 25the literature. It is somewhat elusive however, since it is more difficult to detect. Baseline and followupaudiograms were used to detect high-frequency hearing loss in a case-controlled, retrospectiveanalysis 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 audiogramsand age over 53 years. Long-term follow up and correlation of trough vancomycin concentrationwere not evaluated in the study, but are important considerations.Minimizing toxicity and resistance while improving outcomes is best accomplished by aggressive, empiricdosing based on renal function and actual body weight (table 1), tailoring therapy to MICs and monitoringvancomycin and creatinine concentrations. 13, 31-40 A loading dose of 20 to 25 mg/kg should be considered13,38, 41for critically ill patients in an effort to attain therapeutic concentrations quickly. Patients withpneumonia, meningitis, endocarditis, organisms with MIC ≥ 1 mcg/mL, sepsis, large volumes ofdistribution, body mass index ≥ 30 kg/m 2 , prolonged therapy, renal insufficiency and dialysis requiremonitoring of trough concentrations to ensure adequate concentrations throughout the dosing interval andminimize toxicity. 13Table 1. Adult vancomycin dosing nomogramAdult Vancomycin Dosing Nomogram 38,40Creatinine Clearance* Initial Dose (ABW) † Maintenance Dose(ABW) †≥100 mL/min 15 - 25 mg/kg 10 mg/kg Q 8 h80 - 99 mL/min 15 - 25 mg/kg 15 mg/kg Q 12 h56 - 79 mL/min 15 - 25 mg/kg 10 mg/kg Q 12 h40 - 55 mL/min 15 - 25 mg/kg 15 mg/kg Q 24h30 - 39 mL/min 15 - 25 mg/kg 10 mg/kg Q 24 h20 - 29 mL/min 15 - 25 mg/kg 15 mg/kg Q 48 h30 kg/m 2 , the Salazaar-Corcoran equation is more precise and less biased. 42 For more information;please consult the protocol for renal-based dose adjustments. Renal Function-Based Dose Adjustment inAdults†Round doses down to the nearest 500 mg, 750 mg, 1 g, 1.25 g or 1.5 g dose. If higher single doses arecalculated, then consider giving a smaller dose more frequently. Maximum infusion rate is 10 mg/min orover 1 hour, whichever is longer. Minimum dilution is 5 mg/mL in a peripheral line.