Penetration of meropenem and cefepim into pancreatic tissue during the course of experimental acute pancreatitis

Abstract

Introduction: Recent data from experimental and clinical studies suggest that the antibiotics showing good penetration into the pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis.

Aim: To determine and compare pancreatic tissue concentrations of meropenem and cefepime at different stages of acute necrotizing pancreatitis in an animal model that has been shown to closely mimic severe human pancreatitis.

Methodology: Acute necrotizing pancreatitis was induced in rats by a standardized intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 30) and 48 hours (n = 30) after induction of pancreatitis, the rats were randomized to receive an intravenous 20 mg/kg injection of either meropenem or cefepime. Blood and the head of the pancreas were collected for determining antibiotic concentrations by high-performance liquid chromatography.

Results: Meropenem concentrations in the pancreas at 6 hours of acute pancreatitis increased significantly and decreased at 48 hours of the disease, but were still higher than that in controls. Concentrations of cefepime in necrotic pancreatic tissue were significantly low either during the initial or later phase, but lower in latter, in which the necrosis was more evident. Tissue/serum concentration ratios of meropenem were significantly higher than those of cefepime. However, tissue concentrations of both antibiotics are much higher than the minimum inhibitory concentration values for the common microorganisms involved in pancreatic infections.

Conclusion: Although both antibiotics penetrate into the necrotic tissue in sufficient therapeutic concentrations, penetration of meropenem is much better than cefepime. However, good tissue penetration may not solely indicate efficacy of that antibiotic. Therefore, further experimental and clinical studies are needed to determine the therapeutic and prognostic efficacy of these agents.