Pharmacokinetics of Piperacillin and Ciprofloxacin in Critically Ill Patients Undergoing Continuous Venovenous Haemodialysis or Haemodiafiltration

Florian Scheer

doi:10.4172/2376-0419.1000118

Abstract

In sepsis an early time point of administration, adequate choice of an antibiotic drug and correct dosage are crucial for survival. Acute renal failure in severe sepsis can be treated by continuous renal replacement therapy but interferes with the pharmacokinetics of antibiotic drugs. The aim of the present study was to investigate the efficacy and safety of an antibiotic therapy with piperacillin/tazobactam and ciprofloxacin. In a single-center, prospective, open-label study a total of 24 patients with acute renal failure treated with continuous venovenous haemodialysis (CVVHD) or haemodiafiltration (CVVHDF) were enrolled in a clinical trial. Serum concentrations (Cmax, Cmin) and pharmacokinetic parameters of piperacillin and ciprofloxacin were analyzed. Optimum exposure to piperacillin is expected when serum concentrations are maintained 4-5 times higher than the minimum inhibitory concentration (MIC), i.e. above 64 mg/l. Optimum exposure to ciprofloxacin is given when the ratio (AUIC) of AUC and MIC is ≥ 125 h per dosing interval. In addition the Cmax/MIC ratio should amount to ≥ 10. Plasma concentrations lower than 64 mg/l were determined in 10 out of 21 patients treated with piperacillin. Nine out of 20 patients treated with ciprofloxacin had a calculated AUIC ≥ 125 h and a Cmax/MIC ratio ≥ 10. In critically ill patients undergoing CVVD or CVVDF piperacillin/tazobactam dosing should be increased to 4/0.5 g four times daily and ciprofloxacin dosing to 400 mg twice daily. Therapeutic drug monitoring of antibiotic therapies would be reasonable in these patients. The trial is registered at clinicaltrialsregister.eu ID: 2010-021369-66.

Highlights

Ill intensive care patients are frequently suffering from sepsis and multi organ failure associated with a high mortality rate [1,2,3]
Pharmacokinetic and pharmacodynamic behavior of the antibiotic drugs is affected by acute renal failure (ARF) and by continuous renal replacement therapy (CRRT) [9]
Over a period of twelve months 24 patients were included in the clinical trial. 21 patients were treated with piperacillin/tazobactam and 20 patients were treated with ciprofloxacin

Summary

Introduction

Ill intensive care patients are frequently suffering from sepsis and multi organ failure associated with a high mortality rate [1,2,3]. The initial empiric antibacterial therapy comprises one or more antibiotics that are effective against all likely pathogens causing the infection [4]. While time dependent antibiotics should reach concentrations higher than four times of the minimal inhibition concentration (MIC) of the pathogen, a high ratio of the area under the curve (AUC) to MIC is important for concentration dependent drugs like quinolones [5,6,7,8]. While too low antibiotic concentrations can lead to treatment failures and induce bacteria resistance, too high concentrations can increase side effects and may lead to unnecessary consumption of health care resources. Pharmacokinetic and pharmacodynamic behavior of the antibiotic drugs is affected by acute renal failure (ARF) and by continuous renal replacement therapy (CRRT) [9]

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