ANTIBIOTICS BIOAVAILABILITY IN ACUTE EXPERIMENTAL PANCREATITIS

Pancreatic sepsis in acute pancreatitis is the most lethal complication of the disease. This study was done to create a rational basis for the choice of antibiotics used in the treatment of severe acute pancreatitis. We postulated that, unless the antibiotics were present in therapeutic concentrations in the pancreatic tissue during pancreatitis, their use was of no value. Six mongrel dogs were used to test each antibiotic, each dog acting as its own control. The doses were based on the weight of the dogs: 15.0 milligrams per kilogram of clindamycin; 50.0 milligrams per kilogram of chloramphenicol; 10.0 milligrams per kilogram of metronidazole; 5.0 milligrams per kilogram of gentamicin; 12.5 milligrams per kilogram of cefazolin, and 50.0 milligrams per kilogram of ampicillin. Baseline serum and pancreatic tissue levels were obtained after intravenous injection of the antibiotics. Bile-trypsin hemorrhagic pancreatitis was induced one week later, and the serum and pancreatic tissue level antibiotics were measured again. The results showed significant differences in bioactive levels of antibiotics between blood and the pancreas. Ampicillin, gentamicin and cefazolin reached therapeutic blood levels, but did not achieve a parallel therapeutic level in the normal pancreatic tissue or during pancreatitis. Only three of the antibiotics tested, clindamycin, metronidazole and chloramphenicol, achieved therapeutic tissue penetrance in the normal and inflamed pancreas. After 1982, based on these results, clindamycin became our prophylactic antibiotic of choice in instances of acute severe pancreatitis. This resulted in the eradication of Bacteroides as a cause of pancreatic sepsis between 1980 and 1985. In 1993, our recommendation is to use a broad-spectrum gram-negative and grampositive antibiotic with good penetration of the pancreatic tissue, such as cefotaxime or imipenem.