Prophylactic Oral Antibiotics in Prevention of Recurrent
Cholangitis After the Kasai Portoenterostomy
By Ling-Nan Bu, Huey-Ling Chen, Chee-Jen Chang, Yen-Hsuan Ni, Hong-Yuan Hsu, Hong-Shiee Lai,
Wen-Ming Hsu, and Mei-Hwei Chang
Taipei, Taiwan
Purpose: The aim of this study was to evaluate the efficacy of
trimethoprim-sulfamethoxazole (TMP/SMZ) and neomycin
as the prophylactic agents against the recurrence of cholan-
gitis in children with biliary atresia (BA) after a Kasai por-
toenterostomy.
Methods: Nineteen BA patients aged 0 to 2 years, who had
one episode of cholangitis after a Kasai portoenterostomy,
were recruited in this study. Patients were assigned ran-
domly into 2 groups: one (9 cases) with TMP/SMZ (TMP 4
mg/kg/d and SMZ 20 mg/kg/d, divided in 2 doses) and the
other (10 cases) with neomycin (25 mg/kg/d, qid, 4 days a
week). Another 18 BA patients aged 0 to 2 years, with cholan-
gitis but not put on long-term prophylaxis, served as the
historical control group.
Results: The mean prophylactic periods were 14.6 months
and 14.7 months in the TMP/SMZ and neomycin groups.
B ILIARY ATRESIA (BA) is an idiopathic, progres-
sive, and fatal disease if untreated. Since Kasai first
introduced the operation for BA in 1959, there have been
encouraging results in treating this disease.1 Ascending
cholangitis is a frequent and often recurrent complica-
tion.2,3 It may worsen the prognosis, with an increase in
mortality, secondary failure of restoration of bile flow,
and possible exacerbation of portal hypertension.2,4,5 For
patients who have had restoration of bile flow with a
timely portoenterostomy, the recurrence of ascending
cholangitis is the single most significant variable pertain-
ing to long-term prognosis.6 Patients with multiple epi-
sodes of ascending cholangitis are more likely to require
liver transplantation than those without multiple recur-
rences.7 Therefore, the prevention of cholangitis is cru-
From the Departments of Pediatrics, Pediatric Surgery, and Medical
Research, National Taiwan University Hospital, Taipei, Taiwan
Dr L.N. Bu was a Pediatric GI fellow of the National Taiwan
University Hospital. His current appointment is at the Department of
Pediatrics, Keelung Hospital, Department of Health, the Executive
Yuan, Keelung, Taiwan
Address reprint requests to Mei-Hwei Chang, MD, Department of
Pediatrics, National Taiwan University Hospital, 7F, No. 7, Chung-
Shan South Rd, Taipei 100, Taiwan.
Copyright 2003, Elsevier Science (USA). All rights reserved.
0022-3468/03/3804-0014$30.00/0
doi:10.1053/jpsu.2003.50128
590
Patients who received prophylaxis with either TMP/SMZ or
neomycin had lower recurrence rates of cholangitis than
those in the control group (P .042 and .011). There was no
difference in the recurrence rates of cholangitis between the
TMP/SMZ and neomycin groups (P .641). The survival
rates were higher in the TMP/SMZ and neomycin groups
than in the control group (P .09 and .018).
Conclusions: Use of TMP/SMZ or neomycin is effective as a
prophylactic agent against the recurrence of cholangitis after
the Kasai portoenterostomy, but there is no difference in
efficacy between these 2 regimens.
J Pediatr Surg 38:590-593. Copyright 2003, Elsevier Science
(USA). All rights reserved.
INDEX WORDS: Biliary atresia, portoenterostomy, cholangi-
tis, prophylaxis.
cial in the management of patients who have had a Kasai
portoenterostomy. Some oral antibiotics, like trimeth-
oprim-sulfamethoxazole (TMP/SMZ) and neomycin have
been used as prophylactic agents against ascending
cholangitis, but their efficacy is controversial and lacks a
prospective randomized study.2,8-10 In 1997, we initiated
a prospective randomized study to evaluate the efficacy
of TMP/SMZ and neomycin as prophylactic agents
against ascending cholangitis in children with BA after
the Kasai portoenterostomy.
MATERIALS AND METHODS
From 1997 to 2000, 19 BA patients aged 0 to 2 years, who had one
episode of cholangitis after a Kasai portoenterostomy, were recruited in
this study. They received either TMP/SMZ or neomycin orally for
prophylaxis against recurrent cholangitis until the age of three years.
Patients were assigned randomly into 2 groups: one (9 cases) with
TMP/SMZ (TMP 4 mg/kg/d and SMZ 20 mg/kg/d, divided in 2 doses)
and the other (10 cases) with neomycin (25 mg/kg/d, qid, 4 days a
week). Because of the reported benefit of prophylactic antibiotics for
BA, we treated all cases with prophylactic antibiotics.8,12 In the last 10
years, the treatment for cholangitis in BA patients did not change.
Another 18 BA patients, from 1991 to 1996, aged 0 to 2 years, with
cholangitis but not put on long-term prophylaxis after portoenteros-
tomy, served as the historical control group. Comparisons of the
recurrence of cholangitis were made among the TMP/SMZ, neomycin,
and control groups. All patients were admitted for evaluations and
treatments during individual cholangitis episodes. White blood cell
counts (WBC) with differential counts, C reactive protein (CRP), liver
function tests, and blood and urine cultures were measured. The
Journal of Pediatric Surgery, Vol 38, No 4 (April), 2003: pp 590-593
ORAL ANTIBIOTICS AND CHOLANGITIS 591

Table 1. Demographic Characteristics of Patients in the Three Groups

TMP/SMZ Neomycin Control Group
Demographic Characteristics (n 9) (n 10) (n 18) P Value

Male/Female 6/3 5/5 11/7 .025

Mean SD age at Kasai operation (d) 65.9 32.9 72.1 16.9 66.1 27.3 .845
Mean SD age at first cholangitis (mon) 5.2 2.9 6.1 3.6 6.2 3.2 .209
Mean SD episodes of recurrence 1.3 1.2 1.1 1.8 2.8 1.2 .0001
Mean SD of serum level
Bilirubin (mg/dL) 3.6 3.0 3.1 1.5 3.4 1.7 .246
AST (U/L) 143.7 84.0 124.3 64.7 142.3 64.2 .315
ALT (U/L) 107.2 71.3 111.3 65.6 102.0 36.7 .947
CRP (mg/dL) 3.8 2.2 4.0 4.5 3.3 4.1 .552

Abbreviations: AST, asparatate aminotransferase; ALT, alanine aminotransferase; CRP, C-reactive protein.

diagnosis of cholangitis was made on the basis of unexplained fever 2). The median time to first recurrence of cholangitis was
(38C), acholic stools, increased jaundice, or positive results of blood longer in the TMP/SMZ (6 months) and neomycin (7
culture. Abdominal sonography was performed to detect ascites, intra-
months) groups than in the control (3 months) group, but
hepatic biliary cysts, and signs of liver cirrhosis. Parenteral antibiotic
treatment was used against cholangitis for 2 weeks. Ceftriaxone was only the comparison between neomycin and control
used initially, which later was modified according to the culture results. group was statistically significant (P .058 and .031;
Adverse reactions to TMP/SMZ or neomycin were recorded. Fig 1). The survival rates were higher in the TMP/SMZ
Summary statistics of the demographic variables are presented using and neomycin groups than that in the control group, but
frequency, mean, and standard deviations. Comparisons of these vari-
only the comparison between neomycin and control
ables were made using analysis of variance (ANOVA) and Wilcoxon
rank sum tests, and multiple comparisons were performed if the overall group was statistically significant (P .09 and .018; Fig.
comparison was significant. Recurrence of the disease during the 2). There were one, 2, and 4 cases that received liver
exposure time span and its confidence interval were derived. The transplantation in the TMP/SMZ, neomycin, and control
recurrence rate ratio (RRR) was presented utilizing the Poisson regres- groups, respectively. One patient in the control group
sion approach. A Kaplan-Meier product limit of the time-to-event
died after liver transplantation. No adverse reaction to
method was used to estimate the survival function. The Log-rank test
was used for the comparison of survival function among the 3 groups. the TMP/SMZ or neomycin was noted.
All tests were 2 sided, and P values less than .05 were considered
statistically significant. DISCUSSION
In our study, patients who did not have any prophy-
RESULTS
lactic antibiotics had a higher frequency of recurrence
The demographic characteristics of patients in the 3 episodes of cholangitis and a lower survival rate. The
groups are shown in Table 1. The mean prophylactic
periods were 14.6 months and 14.7 months for the
TMP/SMZ and neomycin groups, respectively. The
mean follow-up durations after the Kasai portoenteros-
tomies were 40.9, 39.5, and 39.0 months in the TMP/
SMZ, neomycin, and control groups, respectively. The
incidence rates of cholangitis were 0.091, 0.075, and
0.175 episodes per person-month in the TMP/SMZ, neo-
mycin, and control groups, respectively. Patients who
received prophylaxis with either TMP/SMZ or neomycin
had lower recurrence rates of cholangitis than those in
the control group (P .042 and .011). There was no
difference in the recurrence rates of cholangitis between
the TMP/SMZ and neomycin groups (P .641; Table

Table 2. Comparisons of the Recurrence Rates of Cholangitis in the

Three Groups
Fig 1. Kaplan-Meier estimates of proportions of patients without
Group RRR P Value 95% CI
recurrence of cholangitis. The median time to first recurrence of
Control 1 cholangitis was longer in the TMP/SMZ (6 months) or neomycin (7
TMP/SMZ 0.52 .042 0.28-0.98 months) groups than in the control (3 months) group, but only the
Neomycin 0.42 .011 0.22-0.82 comparison between the neomycin and control group was statisti-
cally significant (P .058 and .031). (Solid line, TMP/SMZ group;
Abbreviations: RRR, recurrence rate ratio; CI, confidence interval. dashed line, neomycin group; dotted line, control group.)
592
Fig 2. Kaplan-Meier estimates of the probability of survival in the
3 groups. The survival rates were higher in the TMP/SMZ and neo-
mycin groups than in the control group, but only the comparison
between the neomycin and control group was statistically significant
(P .09 and .018). (Solid line, TMP/SMZ group; dashed line, neomy-
cin group; dotted line, control group.)
latter was compatible with previous studies that the more
cholangitis episodes a patient has, the shorter the survival
period.2,6 Therefore, use of TMP/SMZ or neomycin as
the prophylaxis after a Kasai portoenterostomy can offer
some protection against cholangitis and promote the
long-term prognosis. Nevertheless, the control group in
this study is historical, and the progress in postoperative
management and follow-up in more recent years should
be considered.
TMP/SMZ is concentrated in the bile and has been
shown to lower the concentration of bacteria in the bile,
suggesting that this antibiotic combination may be useful
for the management of cholangitis.11 Barkin and Lilly12
recommended continuing TMP/SMZ prophylaxis for at
least one year after a Kasai operation and for 18 months
to 2 years in those who have had recurrent cholangitis.
Nevertheless, the prophylactic effect of TMP/SMZ is
still controversial.2,8-10 TMP/SMZ has been used for
long-term prophylaxis for the prevention of Pneumocys-
tis carinii pneumonia,13 other respiratory infections,14
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BU ET AL
and urinary tract infections.15 In our study, it reduced the
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Neomycin is absorbed poorly when administered
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Some preliminary results are encouraging in a report of
3 cases.8 This also was shown to be effective in our
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The precise mechanism by which ascending cholangi-
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cending cholangitis.17 The prophylactic effect of the
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the bacterial population within the bilioenteric conduit.
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