Variable disposition of ciprofloxacin in critically ill patients undergoing continuous arteriovenous hemodiafiltration.

Continuous arteriovenous hemodiafiltration (CAVHD) is being used increasingly in critically ill patients with acute renal failure (ARF). We prospectively evaluated extracorporeal and total systemic clearances (ClCAVHD and Cls) of ciprofloxacin during CAVHD in four patients with severe ARF to assess the adequacy of drug dosing. Ciprofloxacin serum and ultrafiltrate concentrations were measured by high-performance liquid chromatography. The ClCAVHD accounted for approximately 5.9% (range 2.8-11.6%) of Cls of ciprofloxacin. However, large variability in serum concentrations was observed with the normally recommended dose of 400 mg/day, and doses of up to 800 mg/day were required to maintain concentrations suitable for treatment of serious infections. High daily doses of ciprofloxacin required in these patients are likely related to altered pharmacokinetics in serious illness as well as to the increased extracorporeal clearance during CAVHD. Clinical studies to define appropriate dosing recommendations for ciprofloxacin during CAVHD are necessary to guide clinicians in optimum drug use.