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

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 (C max , C min ) 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 C max /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 C max /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.

Pharmacokinetics of ciprofloxacin during continuous renal replacement therapy in intensive care patients – new assessment

“…In our study the values of pharmacokinetic parameters varied between the patients. A similar large inter-individual variability was also observed by other authors [ 2 , 6 , 10 , 11 ]. Ciprofloxacin is a drug that is mainly excreted by the kidneys, but intestinal and biliary routes as well as metabolic pathways are also involved in its active elimination.…”

“…did not result in optimum PK/PD indices [10,13]. In the paper by Scheer et al discussing pharmacokinetics of ciprofloxacin used in the dose of 400 mg per day in 20 septic patients treated with CVVHD or CVVHDF, only in nine patients did AUC/MIC 0-24 exceed 125 [10]. Many papers define the dosage of ciprofloxacin in the dose of 400 mg i.v.…”

“…According to many papers, a ciprofloxacin dosage of 200 mg b.i.d. did not result in optimum PK/PD indices [ 10 , 13 ]. In the paper by Scheer et al .…”

“…The target for ciprofloxacin is the ratio of AUC 0-24 /MIC of 30-50 for G(+) infections, over 125 for G(-) infections, and in the case of bloodstream infection ≥ 250 [5][6][7][8][9]. Ciprofloxacin efficacy has been also proved in Pseudomonas aureginosa infections when the peak drug concentration in blood exceeds MIC eight-fold (C max /MIC > 8-10) [10]. There is a scarcity of pharmacokinetic studies on ciprofloxacin dosing during CRRT, and these focus primarily on standard dosing (Table 1).…”

Bioanalytical and validation high-performance liquid chromatography method for simultaneous quantification cefotaxime and ciprofloxacin in human plasma

“…Several studies have successfully validated the analytical methods for determining ciprofloxacin levels in various matrices where the equipment used includes HPLC-UV [17][18][19][20][21][22][23][24] and HPTLC [25,26].…”