Variable pharmacokinetics of extended interval tobramycin or gentamicin among critically ill patients undergoing continuous venovenous hemofiltration

Background/Aims: Aminoglycosides are a major weapon against serious Gram-negative rod infections, yet aminoglycoside usage is limited by the risk of nephrotoxicity. The risk of toxicity is reduced by extended-interval dosing of aminoglycosides, defined as 5 - 7 mg/kg given intravenously in intervals of 24 hours or greater based on serum drug concentrations. In critically ill patients undergoing continuous venovenous hemofiltration, there are few published reports of the pharmacokinetics of extended-interval dosing of aminoglycosides. Methods: We evaluated the pharmacokinetics of extended-interval dosing of gentamicin and tobramycin in 9 critically ill patients on continuous venovenous hemofiltration at Dartmouth-Hitchcock Medical Center between April 2007 and September 2011. Results: Aminoglycoside elimination half-life values were highly variable (median 7 hours, range 3 - 26 hours) and did not correlate with total body weight or estimated creatinine clearance derived from the dose of continuous venovenous hemofiltration. Five of 9 patients cleared infection, but only 4 patients survived to hospital discharge, 2 of whom were dialysis-dependent. Conclusion: Extended interval aminoglycoside dosing during continuous venovenous hemofiltration yields unpredictable half-lives and drug levels among high-risk critically ill patients. Close monitoring of serum aminoglycoside levels is required.