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The timing of measurement of peak doses of aminoglycosides with single-daily dosing strategies is not standardized and remains somewhat controversial. Some investigators do not measure therapeutic drug levels at all in patients receiving this dosing strategy. Others recommend at least a single peak measurement to ensure that the blood levels are 10-fold greater than the MIC of the infecting organism. Many investigators recommend at least one or at least a weekly Cmin level obtained at either 12, 18, or 24 hours after the aminoglycoside dose.267–270 The Cmin level should be below the limits of detection of the assay ( <1 µg/ml) at these time intervals.
Measuring aminoglycoside levels with multiple-daily dosing strategies have been standardized for Cmax to be obtained 30 minutes after a 30-minute infusion, and Cmin right before the next dose for trough levels. The aminoglycosides should be administered in patients who are volumereplete; volume depletion increases the risk of nephrotoxicity in experimental studies and is suggested in clinical studies. Additionally, potassium repletion has been shown experimentally and clinically to diminish the risk of AKI related to aminoglycoside administration.
Single-dose daily regimens are difficult to apply in patients with pre-existing kidney disease, and patients with vacillating eGFR and hemodynamics, such as critically ill patients in the ICU setting. The changing pharmacokinetics and pharmacodynamics of antibiotics in general and aminoglycosides in particular, in the critically ill patient, are such that the avoidance of single-daily dosing and application of frequent therapeutic drug monitoring is indicated.322
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