Penetration of Antibiotics into the Pancreas in Rats: An Effect of Acute Necrotizing Pancreatitis

Abstract

Background: Penetration of antibiotics into the pancreas is considered to be an important criterion in determining the most appropriate antibiotic treatment during severe acute pancreatitis. Our study investigated pancreatic penetration of five antibiotics in rats with and without acute necrotizing pancreatitis (ANP) (non-pancreatitis rats (NR), pancreatitis rats (AP)). Methods: ANP was induced by intraductal bile acid injection, and 3 h later the antibiotic was administered. In both NR and AP the antibiotic concentrations were evaluated in blood and pancreatic tissue 90 min after antibiotic administration. Results: The tissue/serum (T/S) ratios for NR were 16% with amikacin, 24% with amoxycillin/clavulanic acid, 27% with piperacillin, 59% with ofloxacin, and 108% with cefoperazone. The ratios for AP were 7%, 23%, 26%, 52%, and 70%, respectively. T/S ratios were similar for NR and AP except for amikacin, for which the T/S ratio was lower in AP than in NR (P = 0.02). Pancreatic tissue concentrations of antibiotics with high penetration rates (cefoperazone and ofloxacin) were sufficient to inhibit most of the pathogens expected during acute pancreatitis. The concentrations of the other antibiotics were less than the minimal inhibitory concentrations (MIC) for common potential pathogens in pancreatic infection. Conclusions: Cefoperazone and ofloxacin showed the best pancreatic penetration of the five antibiotics tested. The high concentrations of these antibiotics in the pancreatic tissue would have enabled efficient antibacterial activity against most of the potential pathogens causing pancreatic infection. An early stage of acute necrotizing pancreatitis did not have a major effect on the pancreatic concentrations of the antibiotics.