Pathogenesis and Prevention of Early Pancreatic Infection in Experimental Acute Necrotizing Pancreatitis

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Abstract
The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxme alone. Renal infection was reduced by both intravenous antibiotics. Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.