STUDY OF LINCOMYCIN CONCENTRATIONS IN HEPATOCYSTIC DUCT

Penetration of lincomycin (LCM) in choledochal and cholecystic bile as well as in the gallbladder tissue and liver tissue was investigated together with bacteria detectable in the bile in order to evaluate basically usefulness of this antibiotic in the treatment of infections of the hepatocystic duct. 1. Intravenous drip infusion of LCM 1.5g (in 500ml of 5% glucose solution) over 1.5-2 hours resulted in mean drug concentrations of 33.9 and 10.1μg/ml in serum at 2 and 4 hours post start of infusion re-spectively; 215.5μg/ml in choledochal bile at 3 hours 15 minutes; 252.7μg/ml in cholecystic bile at 3 hours 36 minutes; 28.1μg/g in gallbladder tissue at 2 hours 55 minutes; and 15.4μg/g in liver tissue at 4 hours. 2. A cross-over study of LCM and cefazolin (CEZ) in 2 cases where T-tubes were employed demonstrat-ed evidently higher biliary levels of LCM than CEZ. 3. Bacteriological examination showed that Hafnia alvei plusStreptococcus faecalts were presented in choledochal bile from just 1 of 4 cases while in cholecystic bile from 9 of 15 cases were detected 22 strains of organisms includingKlebsiella pneumoniae (7 strains),Bacteroides fragilis (5), Escherichia coli (2), Citro-bacter freundii (2) and Serratia marcescens (2). A total of 7 strains of anaerobes including B. fragilis was isolated. 4. The above concentrations of LCM in the bile, gallbladder tissue and liver tissue sufficiently covered the MIC90 of this antibiotic determined by us in 1980 for major species of anaerobes including clinical isolates of B. fragilis. 5. High penetration of LCM in the hepatocystic duct as well as its antibacterial spectrum and mode of action suggested usefulness of this antibiotic in the treatment of anaerobic infections of the hepatocystic duct. Also, LCM was thought very promising as an antibiotic to be used in combination with β-lactam antibiotics in treating mixed aerobic and anaerobic infections because it can eliminate antagonism to help cover a wider range of organisms and also can suppress β-lactamase activity.