title: Time course of bacterial infection of the pancreas and its relation to disease severity in a rodent model of acute necrotizing pancreatitis.
abstract: BACKGROUND
  Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans.
  
  
  OBJECTIVE
  The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis.
  
  
  METHODS
  Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours.
  
  
  RESULTS
  No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours.
  
  
  CONCLUSIONS
  Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston.
authors.forename: T
authors.initials: T
authors.lastname: Foitzik
authors.forename: K
authors.initials: K
authors.lastname: Mithöfer
authors.forename: M J
authors.initials: MJ
authors.lastname: Ferraro
authors.forename: C
authors.initials: C
authors.lastname: Fernández-del Castillo
authors.forename: K B
authors.initials: KB
authors.lastname: Lewandrowski
authors.forename: D W
authors.initials: DW
authors.lastname: Rattner
authors.forename: A L
authors.initials: AL
authors.lastname: Warshaw
mesh_terms: D000208:Acute Disease; D000818:Animals; D001424:Bacterial Infections / Q000473:pathology / Q000503:physiopathology*; D002108:Ceruletide; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D016983:Enterococcus; D004927:Escherichia coli Infections / Q000503:physiopathology; D006002:Glycodeoxycholic Acid; D016908:Gram-Positive Bacterial Infections / Q000503:physiopathology; D007962:Leukocytes / Q000473:pathology; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000503:physiopathology; D015996:Survival Rate; D013997:Time Factors
chemical_list: D006002:Glycodeoxycholic Acid; D002108:Ceruletide