JOURNAL OF SURGICAL RESEARCH 18, 197-200
Evaluation
(1975)
of Prophylactic
RANDOLPH
Antibiotics
in Acute
Pancreatitis
HOWES, M.D., PH.D., GEORGE D. ZUIDEMA, AND JOHN L. CAMERON, M.D.
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. Ninety-five patients were randomized into medical management has become standardized 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 numpancreatitis [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 subsethe 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, nasocomparing 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 antibiotic group and received either ampicillin (44 patients) or lincomycin (four patients), CLINICAL MATERIAL AND while 47 patients received no antibiotic PROTOCOL 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 an160 Caraway units per 100 ml or greater. tibiotic group. This difference was not statisPatients with normal amylase values who tically significant. Alcohol consumption was had their pancreatitis discovered at lap- the most common etiology of the panarotomy, 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 Patients
Age (YI)
Antibiotic
48
37
No antibiotic
47
42
Group0
Race
Sex
46 B 2w 45 B 2w
38M 10F 35M 12F
Initial amyhe value (Caraway units/100 ml) 392 365
aThere was no statistically significant difference in any category between the two groups.
RESULTS 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 remained 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 developed in the antibiotic group, and six in the no-antibiotic group (Table 3). In the antibiotic-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 bacteria cultured was a lactobacillus-sensitive to ampicillin. One patient in the antibiotictreated group developed an ampicillin
allergy and had to be switched to lincomycin. 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 inflammatory process in which bacteria play no etiologic role [lo, 151. Nevertheless, their utilization is thought necessary by most physicians as prophylaxis against secondary infection [7]. During an attack of acute pancreatitis protein-rich exudate collects under the pancreatic capsule, in the retroperitoneum, and in the lesser sac. In addition, in severe episodes parts of the pancreas can become necrotic. Theoretically, this represents an ideal culture medium susceptible to secondary infection. 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 Groupa
Patients
Ethanol
Biliary tract disease
Antibiotic No antibiotic
48 47
45 41
2 3
Idiopathic
Pancreatic carcinoma
1 1
1
aThere was no statistically significant difference in any category between the two groups.
VtlScular
disease 1
HOWE& ZUIDEMA,
AND CAMERON:
ANTIBIOTICS
199
IN PANCREATITIS
TABLE 3 Hospital Course
GroupQ
Patients
Deaths
Hospitalization (days)
Antibiotic No antibiotic
48 41
0 0
9 12
Amylase elevation (days)
Fever (daYSI
Septic complications
2 2
3 3
5 6
‘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 incidence 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 Kodesch 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 evidence 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 selection 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 period between 1972 and 1974. During this interval 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 physicians 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-
holic pancreatitis. The over-all incidence of septic complications in this study was 12%, and 3% of the 95 patients in the study developed 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 elevation, or days of temperature elevation between the antibiotic and no antibiotic groups. The over-all incidknce of septic complications was 10% in the antibiotic-treated group, and 13% in those receiving no antibiotics. This difference was not significant. Two patients in the antibiotic-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 recommended 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 bacterial contamination in pancreatic sepsis is not known, but transmural penetration from the adjacent transverse colon has been suggested [17]. The high incidence of coliform infections reported in pancreatic abscesses supports this thesis [5]. Ampicillin is additionally 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 complications 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 ampicillin. This suggeststhat ampicillin therapy made growing an organism more difficult, and tended to foster the growth of ampicillin-resistant organisms. The results of this prospectively randomized 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 antibiotics 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 become 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. Furthermore, most patients in this series had alcoholic 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 antibiotic coverage had been provided, such as gentamycin and chloromycetin, or gentamycin, 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 apparent, antibiotic therapy along with surgical drainage become mandatory. Prophylactic antibiotic therapy will not decrease the likelihood of an abscessforming, and might make it more difficult to treat because of resistant organisms if one does develop. REFERENCES 1. Altemeier, W. A., and Alexander, J. W. Pancreatic abscess: A study of 32 cases. Arch. Surg. 87:80
(1963). Baker, R. J. Acute surgical diseases of the pancreas. Surg. Clin. North Am. 52~239 (1972). Cogbill, C. L., and Song, K. T. Acute pancreatitis. Arch. Surg. 100:673 (1970). Elmslie, R. G. Aspects of the management of acute pancreatitis. Med. J. Aust. 211(1967). 5. Evans, F. C. Pancreatic abscess. Am. .Z. Surg. 117:537 (1969). 6. Geokas, M. C., Van Lancker, J. L., Kadell, B. M., and Machleder, H. F. Acute pancreatitis. Ann. Zntern. Med 76:105 (1972).
Geokas, M. C. Pancreatitis: Mortality, antibiotics. Ann. Intern. Med. 76:1045 (1972).
Grozinger, K. H. Pancreatitis: Progress in management.Surgery319,1966. Kodesch, R., and DuPont, H. L. Infectious complications of acute pancreatitis. Surg. Gynecol Obstet. 136~763 (1973).
10. Lowenfels, A. B., Rohman, M., and Shibutain, K. Surgical consequences of alcoholism. Surg. Gynecol Obsret. 131:129(1970). 11. Nardi, G. L.: Acute pancreatitis. Surg. Clin. North Am. 46:619 (1966).
12. Nugent, F. W., and Zuberi, S. Treatment of acute pancreatitis.Surg. Clin. North Am. 48:595 (1968). 13. Nugent, F. W. Medical management of acute pancreatitis. Med. Clin. North Am. 53:431 (1969). 14. Rahman, F. Pancreatitis: Mortality, antibiotics. Ann. Intern. Med. 76:1044 (1972): 15. Snodgrass, P. J. Acute pancreatitis, in Harrison’s Principles oflnternal Medicine, 6th ed, Vol. 1, pp. 1578-1582,McGraw-Hill, New York, 1970. 16. Warren, K. W., Veidenheimer, M. C., and Kure, G. A. Management of pancreatitis. N.Y. Slate J. Med. 1174, 1967. 17. Warshaw, A. L. Pancreatic abscesses.N. Engl. J. Med. 287:1234(1972). 18. Zimberg, Y. H. Pancreatitis: Principles of management. Surg. Clin. North Am. 48:889 (1968). 19. Zollinger, R. M. Pancreatic problems 1. Acute pancreatitis. Postgrad. Med. 91(1971).
Evaluation
(1975)
of Prophylactic
RANDOLPH
Antibiotics
in Acute
Pancreatitis
HOWES, M.D., PH.D., GEORGE D. ZUIDEMA, AND JOHN L. CAMERON, M.D.
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. Ninety-five patients were randomized into medical management has become standardized 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 numpancreatitis [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 subsethe 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, nasocomparing 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 antibiotic group and received either ampicillin (44 patients) or lincomycin (four patients), CLINICAL MATERIAL AND while 47 patients received no antibiotic PROTOCOL 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 an160 Caraway units per 100 ml or greater. tibiotic group. This difference was not statisPatients with normal amylase values who tically significant. Alcohol consumption was had their pancreatitis discovered at lap- the most common etiology of the panarotomy, 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 Patients
Age (YI)
Antibiotic
48
37
No antibiotic
47
42
Group0
Race
Sex
46 B 2w 45 B 2w
38M 10F 35M 12F
Initial amyhe value (Caraway units/100 ml) 392 365
aThere was no statistically significant difference in any category between the two groups.
RESULTS 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 remained 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 developed in the antibiotic group, and six in the no-antibiotic group (Table 3). In the antibiotic-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 bacteria cultured was a lactobacillus-sensitive to ampicillin. One patient in the antibiotictreated group developed an ampicillin
allergy and had to be switched to lincomycin. 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 inflammatory process in which bacteria play no etiologic role [lo, 151. Nevertheless, their utilization is thought necessary by most physicians as prophylaxis against secondary infection [7]. During an attack of acute pancreatitis protein-rich exudate collects under the pancreatic capsule, in the retroperitoneum, and in the lesser sac. In addition, in severe episodes parts of the pancreas can become necrotic. Theoretically, this represents an ideal culture medium susceptible to secondary infection. 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 Groupa
Patients
Ethanol
Biliary tract disease
Antibiotic No antibiotic
48 47
45 41
2 3
Idiopathic
Pancreatic carcinoma
1 1
1
aThere was no statistically significant difference in any category between the two groups.
VtlScular
disease 1
HOWE& ZUIDEMA,
AND CAMERON:
ANTIBIOTICS
199
IN PANCREATITIS
TABLE 3 Hospital Course
GroupQ
Patients
Deaths
Hospitalization (days)
Antibiotic No antibiotic
48 41
0 0
9 12
Amylase elevation (days)
Fever (daYSI
Septic complications
2 2
3 3
5 6
‘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 incidence 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 Kodesch 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 evidence 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 selection 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 period between 1972 and 1974. During this interval 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 physicians 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-
holic pancreatitis. The over-all incidence of septic complications in this study was 12%, and 3% of the 95 patients in the study developed 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 elevation, or days of temperature elevation between the antibiotic and no antibiotic groups. The over-all incidknce of septic complications was 10% in the antibiotic-treated group, and 13% in those receiving no antibiotics. This difference was not significant. Two patients in the antibiotic-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 recommended 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 bacterial contamination in pancreatic sepsis is not known, but transmural penetration from the adjacent transverse colon has been suggested [17]. The high incidence of coliform infections reported in pancreatic abscesses supports this thesis [5]. Ampicillin is additionally 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 complications 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 ampicillin. This suggeststhat ampicillin therapy made growing an organism more difficult, and tended to foster the growth of ampicillin-resistant organisms. The results of this prospectively randomized 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 antibiotics 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 become 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. Furthermore, most patients in this series had alcoholic 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 antibiotic coverage had been provided, such as gentamycin and chloromycetin, or gentamycin, 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 apparent, antibiotic therapy along with surgical drainage become mandatory. Prophylactic antibiotic therapy will not decrease the likelihood of an abscessforming, and might make it more difficult to treat because of resistant organisms if one does develop. REFERENCES 1. Altemeier, W. A., and Alexander, J. W. Pancreatic abscess: A study of 32 cases. Arch. Surg. 87:80
(1963). Baker, R. J. Acute surgical diseases of the pancreas. Surg. Clin. North Am. 52~239 (1972). Cogbill, C. L., and Song, K. T. Acute pancreatitis. Arch. Surg. 100:673 (1970). Elmslie, R. G. Aspects of the management of acute pancreatitis. Med. J. Aust. 211(1967). 5. Evans, F. C. Pancreatic abscess. Am. .Z. Surg. 117:537 (1969). 6. Geokas, M. C., Van Lancker, J. L., Kadell, B. M., and Machleder, H. F. Acute pancreatitis. Ann. Zntern. Med 76:105 (1972).
Geokas, M. C. Pancreatitis: Mortality, antibiotics. Ann. Intern. Med. 76:1045 (1972).
Grozinger, K. H. Pancreatitis: Progress in management.Surgery319,1966. Kodesch, R., and DuPont, H. L. Infectious complications of acute pancreatitis. Surg. Gynecol Obstet. 136~763 (1973).
10. Lowenfels, A. B., Rohman, M., and Shibutain, K. Surgical consequences of alcoholism. Surg. Gynecol Obsret. 131:129(1970). 11. Nardi, G. L.: Acute pancreatitis. Surg. Clin. North Am. 46:619 (1966).
12. Nugent, F. W., and Zuberi, S. Treatment of acute pancreatitis.Surg. Clin. North Am. 48:595 (1968). 13. Nugent, F. W. Medical management of acute pancreatitis. Med. Clin. North Am. 53:431 (1969). 14. Rahman, F. Pancreatitis: Mortality, antibiotics. Ann. Intern. Med. 76:1044 (1972): 15. Snodgrass, P. J. Acute pancreatitis, in Harrison’s Principles oflnternal Medicine, 6th ed, Vol. 1, pp. 1578-1582,McGraw-Hill, New York, 1970. 16. Warren, K. W., Veidenheimer, M. C., and Kure, G. A. Management of pancreatitis. N.Y. Slate J. Med. 1174, 1967. 17. Warshaw, A. L. Pancreatic abscesses.N. Engl. J. Med. 287:1234(1972). 18. Zimberg, Y. H. Pancreatitis: Principles of management. Surg. Clin. North Am. 48:889 (1968). 19. Zollinger, R. M. Pancreatic problems 1. Acute pancreatitis. Postgrad. Med. 91(1971).
