Pharmacokinetics and tissue distribution of intravenous pefloxacin for antibiotic prophylaxis in biliary surgery.

摘要

The plasma levels and tissue penetration of pefloxacin were studied after prophylactic administration to patients undergoing elective biliary surgery. Pefloxacin was administered as a single dose of 800 mg given intravenously as an infusion 1 h before surgery. Over a period of two years, cultures of bile and stone were performed after cholecystectomy in order to find the main pathogens present in the geographical area of the hospital of Txagorritxu (Vitoria, Spain), as well as to test the antimicrobial susceptibility of these bacteria to pefloxacin. Thirty seven per cent of the bile and stone cultures were positive, and 75 different species were isolated. E. coli was the predominant microorganism (25%). Other frequent microorganisms were E. faecium (9.3%), S. epidermidis (6.6%) and Cl. perfringens (6.6%). Most species isolated were susceptible to pefloxacin, with MIC(90) values of 0.125 &mgr;g/ml for E. coli, 0.5 &mgr;g/ml for S. epidermidis and 1 &mgr;g/ml for Cl. perfringens. E. faecium was resistant, with a MIC(90) value of 8 &mgr;g/ml but a MIC(50) of 4 &mgr;g/ml (intermediate). After pefloxacin infusion, adequate drug plasma levels (>MIC(90)) for the most frequent pathogens were found throughout the procedure. Elimination half-life was estimated as 22.03+/-6.91 h; the area under the concentration-time curve from zero to infinite had a value of 275.07+/-130.02 mg h/l and the values for volume of distribution at steady-state and plasma clearance were 96.48+/-28.65 L and 3.60+/-1.83 l/h, respectively. Bile pefloxacin concentrations generally exceeded the minimum inhibitory concentrations for most relevant pathogens. Drug levels in gallbladder and subcutaneous tissues were also above the MIC(90) for extended periods. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalization stay and time of recuperation were normal for this type of surgery. According to these results, pefloxacin presents many features that make it suitable for use as a therapeutic prophylactic agent, such as its broad spectrum of antimicrobial activity and favorable pharmacokinetic properties. Copyright 2002 John Wiley & Sons, Ltd.