Evaluation of amikacin dosing schedule in critically ill elderly patients with different stages of renal dysfunction.

OBJECTIVES: Amikacin is still a widely used aminoglycoside for the treatment of life-threatening infections. The pharmacokinetic parameters of this antibiotic may be altered in critically ill conditions. Moreover, in the elderly population, pathophysiological changes affect these pharmacokinetic variables, making it difficult to predict the appropriate dose and dosing schedule for amikacin. This study aimed to characterise the pharmacokinetics of amikacin in critically ill elderly patients with renal dysfunction, and to evaluate if the available dose adjustment schedules dependent on renal function would be appropriate for empirical dosing. METHODS: Critically ill patients aged >60 years with a creatinine clearance of >20 mL/min in need of treatment with amikacin were randomly enrolled. All the patients received approximately 25 mg/kg amikacin. The patients were then divided into three groups according to the stages of their renal dysfunction based on creatinine clearance, and the optimum time to re-dosing was calculated for each group. The pharmacokinetic parameters of the patients were calculated and estimated as population pharmacokinetic data. RESULTS: Of 30 patients, only 20% attained the target peak levels of amikacin of >64 mg/L. In addition, the mean volume of distribution was 0.47 L/kg. There was a poor correlation between amikacin clearance and creatinine clearance. The difference in amikacin half-life was not statistically significant among any of the stages of renal impairment. CONCLUSIONS: The initial dosing of amikacin in critically ill elderly patients should not be reduced, even in the context of renal impairment. Regarding the dose adjustment in renal impairment, dosing intervals estimation, no decision can be made based on the creatinine clearance and the first dose individualisation method in terms of the two-sample measurements may be considered as an appropriate strategy.

Area under the Curve-Based Dosing of Vancomycin in Critically Ill Patients Using 6-Hour Urine Creatinine Clearance Measurement.

BACKGROUND: The area under the curve- (AUC-) guided vancomycin dosing is the best strategy for individualized therapy in critical illnesses. Since AUC can be calculated directly using drug clearance (CLvan), any parameter estimating CLvan will be able to achieve the goal of 24-hour AUC (AUC24 h). The present study was aimed to determine CLvan based on 6-hour urine creatinine clearance measurement in critically ill patients with normal renal function. METHOD: 23 adult critically ill patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min who received vancomycin infusion were enrolled in this pilot study. Vancomycin pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model provided by MONOLIX software using stochastic approximation expectation-maximization (SAEM) algorithm. Correlation of CLvan with the measured creatinine clearance in 6-hour urine collection (CL6 h) and estimated creatinine clearance by the Cockcroft-Gault formula (CLCG) was investigated. RESULTS: Data analysis revealed that CL6 h had a stronger correlation with CLvan rather than CLCG (r = 0.823 vs. 0.594; p < 0.001 vs. 0.003). The relationship between CLvan and CL6 h was utilized to develop the following equation for estimating CLvan: CLvan (mL/min) = ─137.4 + CL6 h (mL/min) + 2.5 IBW (kg) (R 2 = 0.826, p < 0.001). Regarding the described model, the following equation can be used to calculate the empirical dose of vancomycin for achieving the therapeutic goals in critically ill patients without renal impairment: total daily dose of vancomycin (mg) = (─137.4CL6-h (mL/min) + 2.5 IBW (kg)) × 0.06 AUC24 h (mg.hr/L). CONCLUSION: For AUC estimation, CLvan can be obtained by collecting urine in a 6-hour period with good approximation in critically ill patients with normal renal function.