Recommended dose of arbekacin, an aminoglycoside against methicillin-resistantStaphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance

Abstract

To define the pharmacokinetics of arbekacin (ABK), an aminoglycoside, in patients with acutely lowered renal function. We measured the serum concentrations of ABK, using fluorescence polarization immunoassay, in 10 critically ill patients (patient group) and six healthy volunteers (control group). Data were analysed with a two-compartment model and parameters were estimated by the Bayesian method. The Mann-Whitney U-test or chi-squared test was used as appropriate (P < 0.05). Creatinine clearance (CCR), measured or estimated using Cockcroft and Gault's formula of the patient group (CCR: 58 +/- 13 mL/min), was significantly lower than that of the control group (CCR: 99 +/- 8 mL/min). However, despite the low CCR, even the maintenance ABK dosage for normal CCR did not elevate the highest serum level (C(max)) to the effective range in the patient group. Although the ABK clearance (CL) did not differ between the groups, the patients' distribution volume (V(d)) increased significantly compared with the control. The transfer rate constant from central to peripheral compartment (k(12)) in the patient group was much higher than that in the control. In critically ill patients with lowered CCR, the ABK dose for normal CCR subjects does not elevate its serum concentration to effective levels because of augmented V(d) caused by increased k(12). The present results hypothesize that adjustment of antibiotic dosing according to CCR further lowers C(max) in critically ill patients with reduced CCR.