Gentamicin and Renal Function: Lessons From 15 Years' Experience of a Pharmacokinetic Service for Extended Interval Dosing of Gentamicin

Background: Extended interval dosing (EID) of gentamicin most commonly involves dosing every 24 hours, but patients with impaired renal function may require a longer dose interval. This study examines a large database of patients treated with gentamicin from 1996 to 2010 to see how many patients with renal impairment would have benefited from dose intervals >24 hours and to define the incidence of nephrotoxicity. Methods: All patients aged >= 16 years who had received gentamicin by EID over the 14-year period and had concentration data available were examined. End points included the numbers (%) achieving the target peak concentration [predicted maximum gentamicin concentration (C-max)] >10 mg/L, the target trough concentration at 24 hours [predicted minimum gentamicin concentration (C-min24) <0.5 mg/L, and the target area under the curve over 24 hours of 70-100 mg/L.h. How these related to various creatinine clearance (CLcr) groupings was also examined, as was the number who developed nephrotoxicity (increase in creatinine of >= 0.04 mmol/L). Results: After exclusions, information was available on 4523 patients. Of these, 96% achieved the target C-max, 83% the target C-min24, and 54% the target area under the curve over 24 hours. Of the 73% of patients with CLcr >= 60 mL/min, 98% and 97% achieved the target C-max and C-min24, respectively. Of the 19% of patients with CLcr of 40-59 mL/min, 94% and 61% achieved the target C-max and C-min24, respectively. Of the 8% of patients with CLcr of 20-39 mL/min, 83% and 15% achieved the target C-max and C-min24, respectively. Nephrotoxicity, "probably" because of gentamicin, was observed in approximately 4% of the patients studied, which was irreversible in 25% of these (ie, 1% overall). Conclusions: Extending the dose interval of gentamicin to >24 hours is useful in patients with renal impairment to achieve the aims of EID. These results support initial dose intervals for gentamicin of 24, 36, and 48 hours for patients with CLcr >= 60, 40-59, and 20-39 mL/min, respectively. Irreversible nephrotoxicity was observed in approximately 1% of the patients studied.