PATHOGENESIS AND PREVENTION OF EARLY PANCREATIC INFECTION IN EXPERIMENTAL ACUTE NECROTIZING PANCREATITIS

Objective The authors test antibiotic strategies aimed at either mitig ating bacterial translocation from the gut or delivering antibiotics s pecifically concentrated by the pancreas for prevention of early secon dary infection after acute necrotizing pancreatitis. Background Infect ion currently is the principal cause of death after severe pancreatiti s. The authors have shown that the risk of bacterial infection correla tes directly with the degree of tissue injury in a rodent model of pan creatitis. Bacteria most likely arrive by translocation from the colon . Methods Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeo xycholic acid superimposed on intravenous cerulein hyperstimulation. A t 6 hours, animals were randomly allocated to five treatment groups: c ontrols, selective gut decontamination (oral antibiotics and cefotaxim e), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours , surviving animals were killed for quantitative bacterial study of th e cecum, pancreas, and kidney. Results The 95-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria wer e significantly reduced only by the oral antibiotics. Pancreatic infec tion was significantly reduced by full-gut decontamination and by imip enem, but not by oral antibiotics or by cefotaxime alone. Renal infect ion was reduced by both intravenous antibiotics. Conclusions Early pan creatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentr ated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These f indings suggest that 1) both direct bacterial translocation from the o ut and hematogenous seeding interplay in pancreatic infection while he matogenous seeding is dominant at extrapancreatic sites and 2) imipene m may be useful in clinical pancreatitis.