JOURNAL OF SURGICAL RESEARCH 18, 197-200 (1975)

Evaluation of Prophylactic Antibiotics in Acute Pancreatitis

RANDOLPH HOWES, M.D., PH.D., GEORGE D. ZUIDEMA, M.D.,

AND JOHN L. CAMERON, M.D.
Department of Surgery, The Johns Hopkins Medical Institutions,
Baltimore, Maryland 21205
Received November 8,1974

The treatment of acute pancreatitis in clinical diagnosis of acute pancreatitis were

most instances is nonoperative [ll, 131.The included regardless of etiology.
medical management has become stan- Ninety-five patients were randomized into
dardized and includes intravenous fluids, antibiotic and no antibiotic groups on the
nasogastric suction, pain medication, often basis of their history number. Nine patients
anticholinergics, and usually parenteral anti- were excluded from the protocol because of
biotics [6]. Uncomplicated acute pan- physician noncompliance. Those patients
creatitis is a sterile inflammatory process with even history numbers were given 1 g of
and the need for or benefit from antibiotic ampicillin every 6 hr for 5 days. Initially it
therapy in such cases has not been dem- was given intravenously, and then changed
onstrated [3, 91. Secondary infection with to oral administration once the patient was
the development of a pancreatic abscess is eating. If a history of penicillin allergy was
not common, but when it occurs it carries a obtained, or if an allergic reaction developed,
high mortality [5]. In an effort to prevent lincomycin 600 mg was given intravenously
such septic complications most clinicians every 8 hr, and then 500 mg orally every 6 hr
use antibiotics prophylactically in acute for 5 days. Patients with odd history num-
pancreatitis [2, 12, 191.In order to evaluate bers were given no antibiotics. If clinical or
the efficacy of antibiotic administration in bacteriologic evidence of an infection subse-
the treatment of acute pancreatitis, a quently developed, appropriate antibiotic
prospective randomized study was per- therapy was started. In addition, patients
formed at The Johns Hopkins Hospital were treated with intravenous fluids, naso-
comparing the incidence of septic complica- gastric suction, demerol administration, and
tions in patients treated with ampicillin to intramuscular atropine.
those receiving no antibiotic therapy. Forty-eight patients were placed in the an-
tibiotic group and received either ampicillin
CLINICAL MATERIAL AND (44 patients) or lincomycin (four patients),
PROTOCOL while 47 patients received no antibiotic
therapy. The age, race, and sex distributions
This prospective study was carried out within the two groups were similar with no
over a 24-mo period between 1972 and 1974. statistically significant differences (Table 1).
During this interval there were 104 ad- The average initial serum amylase value in
missions with the clinical diagnosis of acute the antibiotic group was 392 Caraway units/
pancreatitis, and with a serum amylase of 100 ml, and 365 Caraway units in the no an-
160 Caraway units per 100 ml or greater. tibiotic group. This difference was not statis-
Patients with normal amylase values who tically significant. Alcohol consumption was
had their pancreatitis discovered at lap- the most common etiology of the pan-
arotomy, or who developed pancreatitis creatitis, being responsible for 45 out of
while in the hospital, were not included in the 48 in the antibiotic group and 41 out of 47 in
study. All other patients admitted with the the no antibiotic group (Table 2).
197
Copyright o 1975 by Academic Press, Inc.
All rights of reproduction in any form reserved.
198 JOURNAL OF SURGICAL RESEARCH VOL. 18, NO. 2, FEBRUARY 1975

TABLE 1
Patients Randomized With Acute Pancreatitis
Age Initial amyhe value
Group0 Patients (YI) Race Sex (Caraway units/100 ml)
Antibiotic 48 37 46 B 38M 392
2w 10F
No antibiotic 47 42 45 B 35M 365
2w 12F
aThere was no statistically significant difference in any category between the two groups.

RESULTS allergy and had to be switched to lin-

There were no deaths in either group. The
average length of hospitalization was 9 days
in the antibiotic group and 12 days in the no
antibiotic group. This difference was not
statistically significant. The amylase re-
mained elevated for an average of 2 days
after admission in both groups. There was an
average of 3 days of fever after admission in
both groups. Five septic complications de-
veloped in the antibiotic group, and six in the
no-antibiotic group (Table 3). In the anti-
biotic-treated group three patients developed
pneumonia. In only one instance was an
organism grown and that proved to be an
ampicillin-resistant Klebsiella. Two patients
in the antibiotic group developed pancreatic
abscesses.In only one case did an organism
grow, once again an ampicillin-resistant
Klebsiella. In the no-antibiotic group there
were four pneumococcal pneumonias, all
sensitive to ampicillin. There was one
pancreatic abscessin the no antibiotic group
secondary to ampicillin-resistant Klebsiella
and Enterobacter. One patient receiving no
antibiotics developed a septicemia, the
source of which was never found. The bac-
teria cultured was a lactobacillus-sensitive to
ampicillin. One patient in the antibiotic-
treated group developed an ampicillin
comycin.
DISCUSSION
The use of antibiotics in the treatment of
acute pancreatitis has become routine [2, 12,
191.This is despite the fact that pancreatitis
is generally accepted to be a sterile inflam-
matory process in which bacteria play no
etiologic role [lo, 151. Nevertheless, their
utilization is thought necessary by most phy-
sicians as prophylaxis against secondary in-
fection [7]. During an attack of acute
pancreatitis protein-rich exudate collects
under the pancreatic capsule, in the retro-
peritoneum, and in the lesser sac. In ad-
dition, in severe episodes parts of the
pancreas can become necrotic. Theoret-
ically, this represents an ideal culture
medium susceptible to secondary infec-
tion. Fortunately, secondary infection is
not common and in less than 5% of all
patients presenting with acute pancreatitis
does an abscessdevelop [l, 171.Other forms
of infection such as pneumonia, urinary
tract infection, and bacteremia are actually
more frequently encountered in patients with
acute pancreatitis.
Prior studies have produced conflicting
data as to the efficacy of prophylactic anti-

TABLE 2
Etiology of Acute Pancreatitis
Collagen
Biliary tract Pancreatic VtlScular
Groupa Patients Ethanol disease Idiopathic carcinoma disease
Antibiotic 48 45 2 1
No antibiotic 47 41 3 1 1 1
aThere was no statistically significant difference in any category between the two groups.
 HOWE& ZUIDEMA, AND CAMERON:
TABLE 3
Hospital Course
Hospitalization
GroupQ Patients Deaths (days)
Antibiotic 48 0 9
No antibiotic 41 0 12
‘There was no statistically significant difference in any category between the two groups.
biotics in acute pancreatitis. Evans [5] from
a literature review and on the basis of his
data felt that antibiotics had reduced the in-
cidence of pancreatic abscessfrom 9 to 3%.
Cogbill and Song [3], however, could find no
statistically significant advantage in the use
of antibiotics in their series of 147 patients
with acute pancreatitis. Most recently Ko-
desch and DuPont [9] have reviewed a series
of 100 patients with acute pancreatitis. The
over-all incidence of bacterial infection was
29%, but only one patient developed a
pancreatic abscess.Sixteen patients had evi-
dence of infection at presentation. Of the
remaining 84 patients, 24 were treated
prophylactically with antibiotics and 60
received none. There was no statistically
significant difference in the incidence of
septic complications between the two
groups. The difficulty with all prior studies is
that they have been retrospective, and se-
lection on clinical grounds has obviously
been used to determine to whom antibiotics
were administered. Therefore, to resolve
whether or not prophylactic antibiotics have
a place in the treatment of acute
pancreatitis, a prospective randomized study
was undertaken.
The study was conducted over a 2-yr pe-
riod between 1972 and 1974. During this in-
terval 104 patients with acute pancreatitis
were admitted, and 95 were randomized on
the basis of history number into antibiotic
and no antibiotic groups. Nine patients were
excluded from the study because their phy-
sicians refused to comply with the protocol.
Most patients presenting to our hospital
with acute pancreatitis have a history of
heavy alcoholic intake, and 90% of the
patients in this study were felt to have alco-
ANTIBIOTICS IN PANCREATITIS 199
Amylase
elevation Fever Septic
(days) (daYSI complications
2 3 5
2 3 6
holic pancreatitis. The over-all incidence of
septic complications in this study was 12%,
and 3% of the 95 patients in the study de-
veloped a pancreatic abscess. The groups
were comparable in age, sex, race, and initial
amylase value. There was no difference in
days of hospitalization, days of amylase ele-
vation, or days of temperature elevation
between the antibiotic and no antibi-
otic groups. The over-all incidknce of sep-
tic complications was 10% in the anti-
biotic-treated group, and 13% in those
receiving no antibiotics. This difference was
not significant. Two patients in the anti-
biotic-treated group and one patient in the
no-antibiotic group developed pancreatic
abscesses.All three patients survived despite
hospitalizations of 16,31, and 44 days.
The choice of antibiotic in this prospective
study was ampicillin. Others have recom-
mended ampicillin for acute pancreatitis [2,
4, 81, but many other regimens have also
been suggested [14, 16, 181.The organisms
cultured in pancreatic abscessestend to be
enteric, and gram-negative rather than
staphylococcal or streptococcal coverage
has to be provided. The source of the bac-
terial contamination in pancreatic sepsis is
not known, but transmural penetration from
the adjacent transverse colon has been sug-
gested [17]. The high incidence of coliform
infections reported in pancreatic abscesses
supports this thesis [5]. Ampicillin is addi-
tionally convenient in that it can be given
intravenously through a peripheral line, and
can be administered orally when the patient
is taking oral fluids. In the five septic com-
plications that developed in the antibiotic
group, an organism was grown in only two
cases.In both instances the organism was an
200 JOURNAL OF SURGICAL RESEARCH VOL. 18, NO. 2, FEBRUARY
ampicillin-resistant bacteria. In the six
septic complications that developed in the
group receiving no antibiotics, an organism
was cultured in each case. In only one
instance was the organism resistant to am-
picillin. This suggeststhat ampicillin therapy
made growing an organism more difficult,
and tended to foster the growth of am-
picillin-resistant organisms.
The results of this prospectively ran-
domized study show no advantage to the use
of antibiotics in the treatment of acute
pancreatitis, and some disadvantage as one
patient receiving ampicillin developed an
allergic reaction. Only three of the patients
in this study developed pancreatic abscesses
and it is only within this small group that an-
tibiotics theoretically could be of value.
Therefore, it is possible that if a much larger
series of patients were studied, an advantage
in the antibiotic-treated group would be-
come apparent. In addition, this group of 95
patients obviously had a mild form of
pancreatitis as there were no deaths, and an
average of only 2 days of amylase elevation.
With a more severe form, antibiotics
possibly could be of more value. Further-
more, most patients in this series had alco-
holic pancreatitis. It is possible that if a
higher proportion had had biliary tract
disease, some benefit from antibiotics could
have been demonstrated. Finally, it is
possible that if a more complete enteric anti-
biotic coverage had been provided, such as
gentamycin and chloromycetin, or gen-
tamycin, penicillin, and clindamycin, an
advantage would have been appreciated.
Such coverage with potentially toxic drugs
appears unwarranted, however, in view of
the small number of patients that actually
develop a pancreatic abscess.It currently is
our recommendation that antibiotics not be
used prophylactically in acute pancreatitis.
In the milder edematous pancreatitis that
was seen predominantly in this study, there
should be no question. In the more severe
hemorrhagic necrotizing pancreatitis, there
still may be a place for broad spectrum
prophylactic antibiotic therapy, and further
study is in order. It is our recommendation,
1975
however, even in the presence of severe
pancreatitis not to use antibiotics until there
is clinical or bacteriologic evidence of sepsis.
When a pancreatic abscess becomes ap-
parent, antibiotic therapy along with sur-
gical drainage become mandatory. Pro-
phylactic antibiotic therapy will not de-
crease the likelihood of an abscessforming,
and might make it more difficult to treat be-
cause of resistant organisms if one does de-
velop.
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