INFLUENCE OF CHANGES IN PANCREATIC TISSUE MORPHOLOGY AND CAPILLARY BLOOD-FLOW ON ANTIBIOTIC TISSUE CONCENTRATIONS IN THE PANCREAS DURING THE PROGRESSION OF ACUTE-PANCREATITIS

Backgrond-The ability of an antibiotic to reach bactericidal concentra tions in tissue depends on numerous factors including tissue compositi on and regional perfusion. Although necrotising pancreatitis is charac terised by progression of pancreatic necrosis over at least 96 hours a nd microcirculatory alterations, the impact of these changes on the co ncentration of antibiotics in the pancreas has not yet been investigat ed. Aim-To determine and compare pancreatic tissue concentrations of i mipenem and cefotaxime at different stages of acute necrotising pancre atitis in an animal model that has been shown to mimic closely the pat homorphological and bacteriological features of severe human pancreati tis. Method-Acute necrotising pancreatitis was induced in rats by a st andardised intraductal infusion of glycodeoxycholic acid and intraveno us cerulein. Six hours (n=16) and 48 hours (n=16) after induction of p ancreatitis, the animals were randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen minutes after injection of the antibiotic, the animals were killed. Blood and the head of the pancrea s were collected for determining imipenem or cefotaxime in serum and t issue; the splenic portion of the pancreas was prepared for histologic al examination. In an additional set of identically treated animals, p ancreatic capillary blood flow (PCBF) was assessed by intravital micro scopy before induction of acute necrotising pancreatitis and at the ti me of antibiotic therapy. Results-Imipenem accumulates in the pancreas in the initial phase of acute necrotising pancreatitis characterised by pronounced oedema and decreased PCBF, and tends to decrease with re solution of the oedema and the progression of acinar cell necrosis in the later course of the disease. Concentrations of cefotaxime are low in oedematous pancreatic tissue early after induction of acute necroti sing pancreatitis and increase with the resolution of oedema and norma lisation of PCBF. Conclusions-Concentrations of antibiotics in the pan creas vary in necrotising pancreatitis, depending on changes in pancre atic tissue morphology and capillary blood flow. This suggests that an tibiotic tissue concentrations may not be consistent from one agent to another and that efficacy of antibiotics in acute pancreatitis cannot be estimated solely on the basis of their pharmacological and microbi ological properties.