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PHC-021 Pharmacokinetics of Piperacillin and Ciprofloxacin in Critically Ill Patients Undergoing Continuous Venovenous Haemodialysis (CVVHD) or Continuous Venovenous Haemodiafiltration (CVVHDF)
  1. F Scheer,
  2. I Kraemer
  1. University Medical Center, Pharmacy Department, Mainz, Germany

Abstract

Background Critically ill patients on intensive care units are often suffering from sepsis and multiorgan failure causing a high mortality rate. In the presence of acute renal failure (ARF) survival can be improved by continuous renal replacement therapy (CRRT). However these procedures are known to be associated with underdosing of the antibiotic agents.

Purpose To investigate the efficacy and safety of antibiotic treatment, especially piperacillin/tazobactam and ciprofloxacin in patients undergoing CRRT.

Materials and Methods A total of 24 patients with ARF treated with CRRT were enrolled in the clinical trial. Plasma and dialysate concentrations of piperacillin/tazobactam and ciprofloxacin were measured in the steady state treatment phase. Serum concentrations of piperacillin and ciprofloxacin were analysed by a validated HPLC method. Optimum exposure to piperacillin is to be expected when serum concentrations are maintained 4–5 times higher than the minimal inhibitory concentration (MIC), i.e. above 64 mg/l. Optimum exposure to ciprofloxacin is given when the ratio (AUIC) of the area under the curve (AUC) and MIC is ≥125 h. In addition the Cmax/MIC ratio should amount to ≥10.

Results For 10 of 21 patients treated with piperacillin/tazobactam 4/0.5g three times a day plasma concentrations lower than 64 mg/l were measured. According to a Clopper-Pearson interval 26–70% of the patients were underdosed and the exposure to piperacillin was too low. Only in 9 of 20 patients treated with ciprofloxacin 200 mg twice per day the calculated AUIC averaged ≥125 h and the Cmax/MIC ratio ≥10. Thereby 29–76% of patients treated with ciprofloxacin were underdosed. With regard to the total body clearance 29% of piperacillin and 16% of ciprofloxacin were eliminated by CRRT. Despite the moderate rate of ClCRRT the exposure of the patients to piperacillin and ciprofloxacin was revealed to be inadequate.

Conclusions In critically ill patients undergoing CRRT for piperacillin/tazobactam increased doses of 4/0.5g four times per day and for ciprofloxacin doses of 400 mg twice per day are recommended.

No conflict of interest.

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