Ascending Cholangitis Following Portoenterostomy

Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many instances, the intrahepatic bile ducts. In the U.S.A., from 400 to 600 new cases of biliary atresia are encountered annually (46). The diagnosis is usually suggested by the persistence of jaundice for six weeks or more after birth. Several factors have been considered for the pathogenesis of extrahepatic biliary atresia, including viral infection (e.g., cytomegalovirus) (47), metabolic insults, and abnormalities in bile duct morphogenesis. Although selected patients benefit from prompt diagnosis and Kasai portoenterostomy surgical intervention (48,49) within the first 60 days of life, many ultimately require liver transplantation because of portal hypertension, recurrent cholangitis, and cirrhosis (50).

Infection of the biliary tract and rarely liver abscess are a known complication following Kasai's procedure. About half of the patients who undergo the Kasai procedure developed postsurgical cholangitis (51). Most episodes occurred within three months of the operation. Factors associated with cholangitis included the degree of restoration of bile flow, abnormal intrahepatic bile ducts or cavities at the porta hepatis, and the postoperative use of antibiotics. External jejunostomy is not effective in preventing cholangitis. Fever decreased bile flow, increased erythrocyte sedimentation rate and signs of shock are frequently observed.

Early bacterial studies of cholangitis following Kasai's procedure revealed coliform bacilli, Proteus spp., and enterococci to be the predominant isolates recovered from these patients (52). However, adequate culture methods for anaerobic bacteria were not performed in most of these studies.

The largest study reporting the bacterial growth within the biliary tract following the Kasai operation was done by Hitch and Lilly (52), who studied 19 patients over 23 months, obtaining 283 cultures. These investigators used methods for recovery of aerobic as well as anaerobic bacteria and reported the colonization of all the bilioenteric conduits with colonic flora within the first postoperative month. E. coli, and Klebsiella, Enterococcus Pseudomonas, Proteus, and Enterobacter spp. were the predominant aerobic isolates. Bacteroides spp., including

B. fragilis, were recovered in 11% of the cultures. These authors report the recovery of similar organisms during episodes of cholangitis.

Brook and Altman studied the aerobic and anaerobic microbiology of the bile duct system in six children with cholangitis following Kasai's procedure (53). Fourteen aerobic bacteria were recovered from all six specimens, and three anaerobic organisms were recovered from three specimens. The predominant aerobes were Klebsiella pneumoniae (4 isolates), Enterococcus spp. (3), and E. coli (2). The anaerobes recovered were B. fragilis (2) and C. perfringens (1). Since that report, we have isolated anaerobes in three more patients, which were two strains of

C. perfringens and one B. fragilis. These findings demonstrate the role of anaerobic organisms in cholangitis following hepatic portoenterostomy.

Studies in adults demonstrated that E. coli, and Klebsiella, Enterobacter, and Enterococcus spp., and anaerobes (B. fragilis group and Clostridium spp.) are the main isolates recovered from patients with biliary tract infection (54-58).

The mechanism by which both aerobic and anaerobic bacteria reach the bile ducts in patients who had undergone Kasai's procedure is probably by an ascending mode from the gastrointestinal tract. This mode of spread is favored by the surgical procedure that approximates a part of the jejunum to the bile system, by the lack of the normal choledochal sphincter action, and by the stasis that can develop after the surgery. Other mechanisms of development of cholangitis are transhepatic filtration of bacteria from the portal venous blood into the cholangiole and periportal lymphatic infection.

The anaerobes recovered in children with ascending cholangitis (52,53) are part of the normal gastrointestinal flora in infants. The initial sterile meconium becomes colonized within 24 hours with aerobic and anaerobic bacteria, predominantly E. coli, Clostridium spp., B. fragilis, and streptococci (59). The isolation rate of B. fragilis and other anaerobic bacteria in the gastrointestinal tract of term babies approaches that of adults within one week (59).

Although the number of infants studied so far is small, the data suggest that anaerobes play a major role in cholangitis following Kasai's procedure, and that specimens obtained from these patients should be cultured routinely for anaerobic as well as aerobic bacteria. It is conceivable that some of the reported failures of conventional antimicrobial therapy to cure patients with postsurgical cholangitis (60) could be due to the lack of use antimicrobial agents effective against anaerobic bacteria, especially those belonging to the B. fragilis group.

While most anaerobic organisms are susceptible to penicillins, members of the B. fragilis group are known to be resistant to these agents (55). In administering therapy to infected patients, consideration should be given to the possible presence of anaerobic organisms. It is reasonable, therefore, to treat children with this infection with antimicrobial agents effective also against B. fragilis and Clostridium spp., at least until results of cultures are known. This includes agents such as clindamycin, metronidazole, the combination of penicillin and a beta-lactamase inhibitor, or a carbapenem.

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