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Antibiotic Therapy in Acute Pancreatitis
Symposium on Surgical Infections and Antibiotics
Antibiotic Therapy in Acute Pancreatitis John L. Cameron, M.D. *, Randolph Howes, M.D., Ph.D., t and George D. Zuidema, M.D.!
Acute pancreatitis is a sterile autodigestive inflammatory process that in most instances runs a self-limited course. Generally accepted treatment modalities include intravenous fluids, nasogastric suction, pain medication and anticholinergic drugs. Although mortality figures as high as 35 per cent in the past were common, in recent years many centers have reported mortalities of less than 10 per cent. A significant proportion of this residual mortality is from sepsis. Septic complications are common in patients with acute pancreatitis. These include pneumonia, urinary tract infection, unexplained bacteremia and pancreatic abscess. Although pancreatic abscesses occur in less than 5 per cent of patients with acute pancreatitis, they are notoriously difficult to diagnose, often require multiple drainage procedures, and carry a high mortality. During an attack of acute pancreatitis protein-rich fluid collects under the pancreatic capsule, in the retroperitoneum, and in the lesser sac. This provides an excellent culture medium and if bacterial seeding occurs, a pancreatic abscess results. In addition, if the attack is severe and areas of the pancreatic parenchyma become hemorrhagic and necrotic, secondary infection is made even more likely. The source of the bacterial contamination in such instances is not clear. Hematogenous spread from a distant site, contamination from the biliary tree, or transmural spread from the adjacent transverse colon have been suggested.9 Most pancreatic abscesses are secondary to enteric organisms, with E. coli being the single most common bacteria cultured. 2 This would seem to favor transmural spread from the transverse colon. Because· of the difficulty in dealing with pancreatic abscesses once they have formed, many clinicians have included prophylactic antibiotics as part of the standard treatment of acute pancreatitis. Others, feelFrom the Department of Surgery, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, Maryland *Associate Professor t Assistant Resident t Professor and Director Surgical Clinics of North America- Vol. 55, No.6, December 1975
1319
1320
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
ing antibiotic therapy does not decrease the incidence of pancreatic abscess formation, have been opposed to their use.
CURRENT PRACTICE Most investigators currently favor the use of prophylactic antibiotics in acute pancreatitis. Evans 2 in 1969 stated that antibiotics had decreased the incidence of pancreatic abscess in acute pancreatitis from 9 per cent in 1950 to less than 3 per cent in 1969. Grozinger'l has recommended broad spectrum parenteral antibiotic therapy for a 10 day period following an attack of acute pancreatitis. Warren et al. 8 and Nugent,7 both of the Lahey Clinic, have recommended cephalothin alone or with colistimethate as routine prophylaxis in acute pancreatitis to lessen the likelihood of abscess formation. Zollinger'O has also recommended antibiotic therapy in an attempt to decrease the septic complications of acute pancreatitis. Nardi,6 quoting the high incidence of mixed enteric flora grown from peritoneal taps early in the course of acute pancreatitis, recommended broad spectrum coverage. Statistical evidence of the benefit of prophylactic antibiotic therapy in acute pancreatitis has been sparse. Cogbill and Song' in a retrospective study could find no statistical evidence of benefit in patients treated prophylactically with antibiotics. Recently Kodesch and DuPont,5 again in a retrospective study, were unable to demonstrate a statistical advantage in those patients with acute pancreatitis treated with antibiotics. In their series there were eight septic complications (33 per cent) among 24 patients receiving prophylactic antibiotics, and 10 septic complications (17 per cent) among 60 patients receiving no antibiotics. This difference in septic complications, favoring the untreated group, was not statistically significant. Evans 2 derived his evidence for a decrease from 9 per cent to 3 per cent in abscess formation in acute pancreatitis by comparing his series to a group of patients published from a different institution 19 years earlier. Warshaw9 has pointed out in a thoughtful review of pancreatic abscess that in the largest reported series of pancreatic abscesses, all patients were treated prophylactically with tetracycline during their antecedent pancreatitis. He further stated that prophylactic antibiotics, while not effective in preventing abscess formation, might be harmful by selecting out resistant organisms.
PROSPECTIVE STUDY Because of the lack of objective· data with which to analyze the efficacy of prophylactic antibiotic therapy in acute pancreatitis, a prospective randomized study was carried out at the Johns Hopkins Hospital. This clinical trial, previously published,4 was carried out between 1972 and 1974. All patients presenting to the Johns Hopkins Hospital with the clinical picture of acute pancreatitis and with a serum amylase of 160 Caraway units, or greater, were included. During this period 104
1321
ANTIBIOTIC THERAPY IN ACUTE PANCREATITIS
Table 1. Acute Pancreatitis-Sample Population
Patients Average Age (years)
Sex Race
PROPHYLACTIC ANTIBIOTICS
NO ANTIBIOTICS
48
47
37
42
38M 10F 46B 2W
35M 12F 45B 2W
consecutive patients meeting these criteria were seen. All patients with even history numbers were given ampicillin, 1 gm., every six hours. Initially it was administered parenterally, but when the patient began oral intake, it was given by mouth. The antibiotic was given for a total of five days, unless a septic complication developed. If sepsis developed, ampicillin or another antibiotic was continued for an appropriate period. Patients with odd history numbers were given no prophylactic antibiotics. If signs of infection developed, antibiotics were administered after appropriate cultures. In addition, all patients were given intravenous support, nasogastric suction, pain medication, and intramuscular atropine. Nine of the 104 patients presenting with acute pancreatitis were not included in the study because of physician noncompliance. Forty eight patients with even history numbers were given antibiotics, and 47 patients with odd history numbers received no antibiotics. These two groups of patients were comparable with no statistically significant differences in age, race, or sex (Table 1). The average adInission serum amylase in the antibiotic group was 392 Caraway units and in the no antibiotic group, 365 Caraway units. In those patients placed on antibiotics the etiology of the pancreatitis in 94 per cent (45 patients) was ethanol ingestion, and in 4 per cent (two patients) biliary tract disease. In the group of patients receiving no antibiotics, 87 per cent (41 patients) had a history of heavy ethanol ingestion and 6 per cent (three patients) biliary tract disease. The remaining patients had a variety of causes for their pancreatitis. There were no deaths in the. 104 consecutive patients presenting with acute pancreatitis during the period of the clinical protocol. This emphasizes the lower mortalities currently being achieved with inflammatory disease of the pancreas. In those patients receiving antibiotics, the average length of hospitalization was 9 days. In the no antibiotic group, the average length of hospitalization was 12 days. Because of the wide spread of days in the hospital ranging from two days to several weeks, these differences in length of hospital stay were not statistically significant between the two groups. Serum amylase values remained elevated for an average of two days in both groups. None of the patients in this study developed pseudocysts, and there were no prolonged serum amylase elevations. In both groups of patients an average of three days of fever followed admission. Among the 95 patients who were included in the clinical protocol, 12 per cent (11 patients) developed septic complications. Five of the pa-
1322
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
Table 2. Acute Pancreatitis - Incidence of Septic Complications PROPHYLACTIC
Patients Deaths Hospitalization (days) Amylase elevation (days) Fever (days) Septic complications
ANTIBIOTICS
NO ANTIBIOTICS
48
47
o
o
9 2 3
12 2 3 6
5
tients (10 per cent) were in the 48 patients treated with antibiotics, and six (13 per cent) were among the 47 patients receiving no antibiotics. There was no statistically significant difference in the incidence of septic complications in acute pancreatitis in patients receiving prophylactic antibiotics, when compared to patients receiving no antibiotic therapy (Table 2). In the five septic complications in the antibiotic treated group, three patients developed pneumonia and two developed a pancreatic abscess. Of the six septic complications in the patients receiving no antibiotic therapy, four patients developed pneumonia, one patient had a bacteremia the source of which was never found, and one patient developed a pancreatic abscess. Interestingly, of the six patients receiving no antibiotics who developed septic complications, in five instances the organism was sensitive to ampicillin, and in one instance the organism was ampicillin resistant. Among the five septic complications in the antibiotic group, in three instances no organisms could be cultured, and in the other two the organisms were resistant to ampicillin (Table 3). One patient in the antibiotic group developed an allergic reaction to ampicillin. Ampicillin has been recommended by many investigators as the drug of choice in patients with acute pancreatitis. Most E. coli organisms are sensitive to ampicillin, and E. coli is the single most common organism cultured from pancreatic abscesses. Also, ampicillin has the advantage that it can be given safely through a peripheral intravenous line initially, and then switched to oral intake when the patient is eating. There are other antibiotic regimens that would more closely cover
Table 3. Acute Pancreatitis-Septic Complications in 11 Patients PROPHYLACTIC ANTIBIOTICS
Pneumonia-no growth Pneumonia-no growth Pneumonia- Klebsiella Abscess-no growth Abscess - Klebsiella
NO ANTIBIOTICS
Pneumonia- Pneumococcus Pneumonia- Pneumococcus Pneumonia- Pneumococcus Pneumonia- Pneumococcus Bacteremia- Lactobacillus Abscess - Klebsiella, Enterobacter
ANTIBIOTIC THERAPY IN ACUTE PANCREATITIS
1323
all organisms found in pancreatic abscesses. The flora found in abscesses is usually enteric. A combination of an amino glycoside and clindamycin with penicillin or an amino glycoside with chloramphenicol would come the closest to covering all the aerobic and anaerobic organisms found in pancreatic abscesses. It is possible that such a combination of antibiotics should be used in all patients with pancreatitis. Since less than 5 per cent of all patients with pancreatitis develop abscesses, however, to expose the entire population of patients to these potentially toxic drugs seems unwarranted. It is certainly unlikely that any statistical advantage to such a combination of drugs could have been demonstrated in this study, since only 3 (3 per cent) of the 95 patients developed a pancreatic abscess. In addition, there are possible disadvantages to the use of antibiotics in acute pancreatitis. The selection of resistant organisms is a possibility suggested by Warshaw. 9 In our study, in two of the five septic complications in the antibiotic treated group the organisms were resistant to the ampicillin the patient was receiving, and in the other three patients no organism could be cultured. In contrast, in five of the six patients who developed sepsis while not receiving antibiotics the organism was ampicillin sensitive. It is possible that by using very broad spectrum enteric antibiotic coverage, resistant organisms very difficult to treat would be selected. Finally, a significant proportion of all patients receiving antibiotics will have an adverse reaction. In studies involving large populations of patients, ampicillin has been found to cause adverse reactions in as many as 5.7 per cent of all patients. There was one allergic reaction (2.1 per cent) among the patients receiving antibiotics in our study. Since there were no deaths in our series of consecutive patients, one might argue that we were dealing with a mild form of pancreatitis where antibiotics are not needed. Our absence of mortality, however, is probably more a reflection of the improvement in survival generally being seen in many centers. It is possible, however, that if one alternated antibiotic use only in patients severely ill with acute hemorrhagic pancreatitis, and eliminated those only mildly ill with edematous pancreatitis, a statistically significant difference could be seen.
RECOMMENDATIONS We currently recommend that prophylactic antibiotics not be used in acute pancreatitis. The above prospective study presents strong evidence in support of this regimen. In hemorrhagic pancreatitis when the patient is severely ill, broad spectrum coverage might be of benefit and further study of this should be undertaken. However, even in this group of patients with more severe disease, we feel presently that prophylactic antibiotics should not be used. If clinical, radiologic or bacteriologic evidence of an abscess develops, then appropriate coverage should be instituted and immediate surgical drainage carried out. It appears from available data that prophylactic antibiotics in acute pancreatitis do not
1324
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
prevent abscess formation, and might make it more difficult to treat because of resistant organisms if one does form.
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Cogbill, C. L., and Song, K. T.: Acute pancreatitis. Arch. Surg., 100:673,1970. Evans, F. C.: Pancreatic abscess. Amer. J. Surg., 117:537,1969. Grozinger, K. H.: Pancreatitis: progress in management. Surgery, 59:319,1966. Howes, R., Zuidema, G. D., and Cameron, J. L.: Evaluation of prophylactic antibiotics in acute pancreatitis. J. Surg. Res., in press. Kodesch, R., and DuPont, H. L.: Infectious complications of acute pancreatitis. Surg. GynecoL Obstet., 131 :763,1973. Nardi, G. L.: Acute pancreatitis. SURG. CLINICS N. AMER., 46:619,1966. Nugent, F. W.: Medical management of acute pancreatitis. Med. Clinics N. Amer., 53:431,1969. Warren, K. W., Veidenheimer, M. C., and Kune, G. A.: Management of pancreatitis. New York State J. Med., 67:1174,1967. Warshaw, A. L.: Pancreatic abscesses. New Eng. J. Med., 287:1234,1972. Zollinger, R. M.: Pancreatic problems. Postgrad. Med., 49:91,1971.
Department of Surgery The Johns Hopkins Medical Institutions Baltimore, Maryland 21205
Antibiotic Therapy in Acute Pancreatitis John L. Cameron, M.D. *, Randolph Howes, M.D., Ph.D., t and George D. Zuidema, M.D.!
Acute pancreatitis is a sterile autodigestive inflammatory process that in most instances runs a self-limited course. Generally accepted treatment modalities include intravenous fluids, nasogastric suction, pain medication and anticholinergic drugs. Although mortality figures as high as 35 per cent in the past were common, in recent years many centers have reported mortalities of less than 10 per cent. A significant proportion of this residual mortality is from sepsis. Septic complications are common in patients with acute pancreatitis. These include pneumonia, urinary tract infection, unexplained bacteremia and pancreatic abscess. Although pancreatic abscesses occur in less than 5 per cent of patients with acute pancreatitis, they are notoriously difficult to diagnose, often require multiple drainage procedures, and carry a high mortality. During an attack of acute pancreatitis protein-rich fluid collects under the pancreatic capsule, in the retroperitoneum, and in the lesser sac. This provides an excellent culture medium and if bacterial seeding occurs, a pancreatic abscess results. In addition, if the attack is severe and areas of the pancreatic parenchyma become hemorrhagic and necrotic, secondary infection is made even more likely. The source of the bacterial contamination in such instances is not clear. Hematogenous spread from a distant site, contamination from the biliary tree, or transmural spread from the adjacent transverse colon have been suggested.9 Most pancreatic abscesses are secondary to enteric organisms, with E. coli being the single most common bacteria cultured. 2 This would seem to favor transmural spread from the transverse colon. Because· of the difficulty in dealing with pancreatic abscesses once they have formed, many clinicians have included prophylactic antibiotics as part of the standard treatment of acute pancreatitis. Others, feelFrom the Department of Surgery, The Johns Hopkins University School of Medicine and The Johns Hopkins Hospital, Baltimore, Maryland *Associate Professor t Assistant Resident t Professor and Director Surgical Clinics of North America- Vol. 55, No.6, December 1975
1319
1320
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
ing antibiotic therapy does not decrease the incidence of pancreatic abscess formation, have been opposed to their use.
CURRENT PRACTICE Most investigators currently favor the use of prophylactic antibiotics in acute pancreatitis. Evans 2 in 1969 stated that antibiotics had decreased the incidence of pancreatic abscess in acute pancreatitis from 9 per cent in 1950 to less than 3 per cent in 1969. Grozinger'l has recommended broad spectrum parenteral antibiotic therapy for a 10 day period following an attack of acute pancreatitis. Warren et al. 8 and Nugent,7 both of the Lahey Clinic, have recommended cephalothin alone or with colistimethate as routine prophylaxis in acute pancreatitis to lessen the likelihood of abscess formation. Zollinger'O has also recommended antibiotic therapy in an attempt to decrease the septic complications of acute pancreatitis. Nardi,6 quoting the high incidence of mixed enteric flora grown from peritoneal taps early in the course of acute pancreatitis, recommended broad spectrum coverage. Statistical evidence of the benefit of prophylactic antibiotic therapy in acute pancreatitis has been sparse. Cogbill and Song' in a retrospective study could find no statistical evidence of benefit in patients treated prophylactically with antibiotics. Recently Kodesch and DuPont,5 again in a retrospective study, were unable to demonstrate a statistical advantage in those patients with acute pancreatitis treated with antibiotics. In their series there were eight septic complications (33 per cent) among 24 patients receiving prophylactic antibiotics, and 10 septic complications (17 per cent) among 60 patients receiving no antibiotics. This difference in septic complications, favoring the untreated group, was not statistically significant. Evans 2 derived his evidence for a decrease from 9 per cent to 3 per cent in abscess formation in acute pancreatitis by comparing his series to a group of patients published from a different institution 19 years earlier. Warshaw9 has pointed out in a thoughtful review of pancreatic abscess that in the largest reported series of pancreatic abscesses, all patients were treated prophylactically with tetracycline during their antecedent pancreatitis. He further stated that prophylactic antibiotics, while not effective in preventing abscess formation, might be harmful by selecting out resistant organisms.
PROSPECTIVE STUDY Because of the lack of objective· data with which to analyze the efficacy of prophylactic antibiotic therapy in acute pancreatitis, a prospective randomized study was carried out at the Johns Hopkins Hospital. This clinical trial, previously published,4 was carried out between 1972 and 1974. All patients presenting to the Johns Hopkins Hospital with the clinical picture of acute pancreatitis and with a serum amylase of 160 Caraway units, or greater, were included. During this period 104
1321
ANTIBIOTIC THERAPY IN ACUTE PANCREATITIS
Table 1. Acute Pancreatitis-Sample Population
Patients Average Age (years)
Sex Race
PROPHYLACTIC ANTIBIOTICS
NO ANTIBIOTICS
48
47
37
42
38M 10F 46B 2W
35M 12F 45B 2W
consecutive patients meeting these criteria were seen. All patients with even history numbers were given ampicillin, 1 gm., every six hours. Initially it was administered parenterally, but when the patient began oral intake, it was given by mouth. The antibiotic was given for a total of five days, unless a septic complication developed. If sepsis developed, ampicillin or another antibiotic was continued for an appropriate period. Patients with odd history numbers were given no prophylactic antibiotics. If signs of infection developed, antibiotics were administered after appropriate cultures. In addition, all patients were given intravenous support, nasogastric suction, pain medication, and intramuscular atropine. Nine of the 104 patients presenting with acute pancreatitis were not included in the study because of physician noncompliance. Forty eight patients with even history numbers were given antibiotics, and 47 patients with odd history numbers received no antibiotics. These two groups of patients were comparable with no statistically significant differences in age, race, or sex (Table 1). The average adInission serum amylase in the antibiotic group was 392 Caraway units and in the no antibiotic group, 365 Caraway units. In those patients placed on antibiotics the etiology of the pancreatitis in 94 per cent (45 patients) was ethanol ingestion, and in 4 per cent (two patients) biliary tract disease. In the group of patients receiving no antibiotics, 87 per cent (41 patients) had a history of heavy ethanol ingestion and 6 per cent (three patients) biliary tract disease. The remaining patients had a variety of causes for their pancreatitis. There were no deaths in the. 104 consecutive patients presenting with acute pancreatitis during the period of the clinical protocol. This emphasizes the lower mortalities currently being achieved with inflammatory disease of the pancreas. In those patients receiving antibiotics, the average length of hospitalization was 9 days. In the no antibiotic group, the average length of hospitalization was 12 days. Because of the wide spread of days in the hospital ranging from two days to several weeks, these differences in length of hospital stay were not statistically significant between the two groups. Serum amylase values remained elevated for an average of two days in both groups. None of the patients in this study developed pseudocysts, and there were no prolonged serum amylase elevations. In both groups of patients an average of three days of fever followed admission. Among the 95 patients who were included in the clinical protocol, 12 per cent (11 patients) developed septic complications. Five of the pa-
1322
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
Table 2. Acute Pancreatitis - Incidence of Septic Complications PROPHYLACTIC
Patients Deaths Hospitalization (days) Amylase elevation (days) Fever (days) Septic complications
ANTIBIOTICS
NO ANTIBIOTICS
48
47
o
o
9 2 3
12 2 3 6
5
tients (10 per cent) were in the 48 patients treated with antibiotics, and six (13 per cent) were among the 47 patients receiving no antibiotics. There was no statistically significant difference in the incidence of septic complications in acute pancreatitis in patients receiving prophylactic antibiotics, when compared to patients receiving no antibiotic therapy (Table 2). In the five septic complications in the antibiotic treated group, three patients developed pneumonia and two developed a pancreatic abscess. Of the six septic complications in the patients receiving no antibiotic therapy, four patients developed pneumonia, one patient had a bacteremia the source of which was never found, and one patient developed a pancreatic abscess. Interestingly, of the six patients receiving no antibiotics who developed septic complications, in five instances the organism was sensitive to ampicillin, and in one instance the organism was ampicillin resistant. Among the five septic complications in the antibiotic group, in three instances no organisms could be cultured, and in the other two the organisms were resistant to ampicillin (Table 3). One patient in the antibiotic group developed an allergic reaction to ampicillin. Ampicillin has been recommended by many investigators as the drug of choice in patients with acute pancreatitis. Most E. coli organisms are sensitive to ampicillin, and E. coli is the single most common organism cultured from pancreatic abscesses. Also, ampicillin has the advantage that it can be given safely through a peripheral intravenous line initially, and then switched to oral intake when the patient is eating. There are other antibiotic regimens that would more closely cover
Table 3. Acute Pancreatitis-Septic Complications in 11 Patients PROPHYLACTIC ANTIBIOTICS
Pneumonia-no growth Pneumonia-no growth Pneumonia- Klebsiella Abscess-no growth Abscess - Klebsiella
NO ANTIBIOTICS
Pneumonia- Pneumococcus Pneumonia- Pneumococcus Pneumonia- Pneumococcus Pneumonia- Pneumococcus Bacteremia- Lactobacillus Abscess - Klebsiella, Enterobacter
ANTIBIOTIC THERAPY IN ACUTE PANCREATITIS
1323
all organisms found in pancreatic abscesses. The flora found in abscesses is usually enteric. A combination of an amino glycoside and clindamycin with penicillin or an amino glycoside with chloramphenicol would come the closest to covering all the aerobic and anaerobic organisms found in pancreatic abscesses. It is possible that such a combination of antibiotics should be used in all patients with pancreatitis. Since less than 5 per cent of all patients with pancreatitis develop abscesses, however, to expose the entire population of patients to these potentially toxic drugs seems unwarranted. It is certainly unlikely that any statistical advantage to such a combination of drugs could have been demonstrated in this study, since only 3 (3 per cent) of the 95 patients developed a pancreatic abscess. In addition, there are possible disadvantages to the use of antibiotics in acute pancreatitis. The selection of resistant organisms is a possibility suggested by Warshaw. 9 In our study, in two of the five septic complications in the antibiotic treated group the organisms were resistant to the ampicillin the patient was receiving, and in the other three patients no organism could be cultured. In contrast, in five of the six patients who developed sepsis while not receiving antibiotics the organism was ampicillin sensitive. It is possible that by using very broad spectrum enteric antibiotic coverage, resistant organisms very difficult to treat would be selected. Finally, a significant proportion of all patients receiving antibiotics will have an adverse reaction. In studies involving large populations of patients, ampicillin has been found to cause adverse reactions in as many as 5.7 per cent of all patients. There was one allergic reaction (2.1 per cent) among the patients receiving antibiotics in our study. Since there were no deaths in our series of consecutive patients, one might argue that we were dealing with a mild form of pancreatitis where antibiotics are not needed. Our absence of mortality, however, is probably more a reflection of the improvement in survival generally being seen in many centers. It is possible, however, that if one alternated antibiotic use only in patients severely ill with acute hemorrhagic pancreatitis, and eliminated those only mildly ill with edematous pancreatitis, a statistically significant difference could be seen.
RECOMMENDATIONS We currently recommend that prophylactic antibiotics not be used in acute pancreatitis. The above prospective study presents strong evidence in support of this regimen. In hemorrhagic pancreatitis when the patient is severely ill, broad spectrum coverage might be of benefit and further study of this should be undertaken. However, even in this group of patients with more severe disease, we feel presently that prophylactic antibiotics should not be used. If clinical, radiologic or bacteriologic evidence of an abscess develops, then appropriate coverage should be instituted and immediate surgical drainage carried out. It appears from available data that prophylactic antibiotics in acute pancreatitis do not
1324
JOHN
L.
CAMERON, RANDOLPH HOWES, AND GEORGE
D.
ZUIDEMA
prevent abscess formation, and might make it more difficult to treat because of resistant organisms if one does form.
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Cogbill, C. L., and Song, K. T.: Acute pancreatitis. Arch. Surg., 100:673,1970. Evans, F. C.: Pancreatic abscess. Amer. J. Surg., 117:537,1969. Grozinger, K. H.: Pancreatitis: progress in management. Surgery, 59:319,1966. Howes, R., Zuidema, G. D., and Cameron, J. L.: Evaluation of prophylactic antibiotics in acute pancreatitis. J. Surg. Res., in press. Kodesch, R., and DuPont, H. L.: Infectious complications of acute pancreatitis. Surg. GynecoL Obstet., 131 :763,1973. Nardi, G. L.: Acute pancreatitis. SURG. CLINICS N. AMER., 46:619,1966. Nugent, F. W.: Medical management of acute pancreatitis. Med. Clinics N. Amer., 53:431,1969. Warren, K. W., Veidenheimer, M. C., and Kune, G. A.: Management of pancreatitis. New York State J. Med., 67:1174,1967. Warshaw, A. L.: Pancreatic abscesses. New Eng. J. Med., 287:1234,1972. Zollinger, R. M.: Pancreatic problems. Postgrad. Med., 49:91,1971.
Department of Surgery The Johns Hopkins Medical Institutions Baltimore, Maryland 21205