Biliary flora and antimicrobial concentrations after Kasai's operation

Abstract

In 1976, a prospective study of children following hepatic portoenterostomy was initiated to determine (1) the efficacy of hepatic antimicrobial excretion, (2) the relationship of antimicrobial levels in bile to bilirubin clearance, and (3) the effect of antimicrobials in bile on the growth of bacteria within the bilioenteric conduit. Fifty simultaneous blood-bile peak-trough antimicrobial levels were assayed in 10 patients. Cephalosporin, aminoglycoside, and trimethoprim-sulfamethoxazole levels were determined 20, 19, and 4 times, respectively. Simultaneous quantitative bile cultures and bilirubin clearance measurements also were obtained. Adequate mean antimicrobial concentrations in serum were achieved. Detectable antimicrobial concentrations in bile were found in 100% of the patients receiving trimethoprim-sulfamethoxazole, 65% of those receiving cephalosporins, and 10% receiving aminoglycosides. Mean bile levels for each antimicrobial were always less than simultaneous serum levels. The mean bile to serum ratios of trimethoprim-sulfamethoxazole, cephalosporins, and aminoglycosides were 0.90, 0.32, and 0.01, respectively. There was no correlation between bilirubin clearance and antimicrobial levels in bile. The presence of antimicrobials in bile did not alter the frequency, type, or concentration of bacterial growth within the bilioenteric conduit. Antimicrobial activity in bile after hepatic portoenterostomy is characterized by: (1) moderate concentrations of trimethoprim-sulfamethoxazole and cephalosporins and low levels of aminoglycosides, (2) the independence of bilirubin clearance and antimicrobial bile concentrations, and (3) the inability to eliminate bacterial growth within the bilioenteric conduit with the achieved biliary antimicrobial levels.