Background: Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to… Click to show full abstract
Background: Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg × h/L has emerged as a more robust dosing target. A simple and practical method to extrapolate AUC24 from troughs is needed. Methods: This mathematical model computes the median and range AUC24 using the dose in mg/kg and the observed serum trough concentration. AUC24 is calculated using dose in mg/kg divided by the volume of distribution (Vd) and elimination constant (Ke). Vd is provided using the population median (range) of 0.7 (0.4–1) L/kg. Ke is calculated using the trough and population Vd. Results: For doses of 15–20 mg/kg, troughs of at least 11 mg/L will achieve AUC24 of greater than 400 mg × h/L, even with a Vd of 1 L/kg. Using the median Vd and lower, AUC24 greater than 400 mg × h/L can be achieved with troughs as little as 9 mg/L using doses of 15 mg/kg and greater. The AUC24:MIC goal of greater than 400 can still be attained with an MIC of 1.5 mg/L by using doses of at least 15 mg/kg and targeting troughs of at least 16 mg/L for a patient with a Vd of 0.7 L/kg or less. Conclusions: Troughs of 15–20 mg/L are rarely needed for organisms with an MIC of 1 mg/L or less. AUC24:MIC goals of greater than 400 can best be achieved with higher doses in mg/kg while targeting lower troughs.
               
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