BEHAVIOR OF ANTIBIOTICS DURING HUMAN NECROTIZING PANCREATITIS

The aim of the study was to verify whether antibiotics excreted by the normal pancreas are also excreted in human necrotizing pancreatitis, reaching the tissue sites of the infection. Twelve patients suffering from acute necrotizing pancreatitis were treated with imipenem-cilasta tin (0.5 g), mezlocillin (2 g), gentamicin (0.08 g), amikacin (0.5 g), pefloxacin (0.4 g), and metronidazole (0.5 g). Serum and necrotic sam ples were collected simultaneously at different time intervals after p arenteral drug administration by computed tomography-guided needle asp iration, intraoperatively, and from surgical drainages placed during s urgery. Drug concentrations were determined by microbiological and hig h-performance liquid chromatography assays. All antibiotics reached th e necrotic tissues, but with varying degrees of penetration, this bein g low for aminoglycosides (13%) and high in the case of pefloxacin (89 %) and metronidazole (99%). The concentrations of pefloxacin (13.0 to 23 mug/g) and metronidazole (8.4 mug/g) in the necrotic samples were d istinctly higher than the MICs for the organisms most commonly isolate d in this disease; the concentrations in tissue of imipenem (3.35 mug/ g) and mezlocillin (8.0 and 15.0 mug/g) did not always exceed the MICs for 90% of strains tested, whereas the aminoglycoside concentrations in necrotic tissue (0.5 mug/g) were inadequate. Repeated administratio n of drugs (for 3, 7, 17, and 20 days) seems to enhance penetration of pefloxacin, imipenem, and metronidazole into necrotic pancreatic tiss ue. The choice of antibiotics in preventing infected necrosis during n ecrotizing pancreatitis should be based on their antimicrobial activit y, penetration rate, persistence, and therapeutic concentrations in th e necrotic pancreatic area. These requisites are provided by pefloxaci n and metronidazole and to a variable extent by imipenem and mezlocill in.