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Transcript
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 ≥ 1 mcg/mL, sepsis, large volumes of
distribution, body mass index ≥ 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*
≥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)†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 – 20 mg/kg or 1 g
CRRT
15 – 20 mg/kg
Maintenance Dose(ABW)†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 – 24 h
Monitor serum concentrations
ABW – actual body weight, CRRT – 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
†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.