Influence of changes in pancreatic tissue morphology and capillary blood flow on antibiotic tissue concentrations in the pancreas during the progression of acute pancreatitis.
BACKGROUND
The ability of an antibiotic to reach bactericidal concentrations in tissue depends on numerous factors including tissue composition and regional perfusion. Although necrotising pancreatitis is characterised by progression of pancreatic necrosis over at least 96 hours and microcirculatory alterations, the impact of these changes on the concentration of antibiotics in the pancreas has not yet been investigated.


OBJECTIVE
To determine and compare pancreatic tissue concentrations of imipenem and cefotaxime at different stages of acute necrotising pancreatitis in an animal model that has been shown to mimic closely the pathomorphological and bacteriological features of severe human pancreatitis.


METHODS
Acute necrotising pancreatitis was induced in rats by a standardised intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 16) and 48 hours (n = 16) after induction of pancreatitis, 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 pancreas were collected for determining imipenem or cefotaxime in serum and tissue; the splenic portion of the pancreas was prepared for histological examination. In an additional set of identically treated animals, pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy before induction of acute necrotising pancreatitis and at the time 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 resolution 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 necrotising pancreatitis and increase with the resolution of oedema and normalisation of PCBF.


CONCLUSIONS
Concentrations of antibiotics in the pancreas vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue morphology and capillary blood flow. This suggests that antibiotic 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 microbiological properties.
Foitzik
T
T
Department of Surgery, Freie Universität Berlin, Germany.
Hotz
H G
HG
Kinzig
M
M
Sörgel
F
F
Buhr
H J
HJ
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000627:therapeutic use; D002196:Capillaries; D002439:Cefotaxime / Q000032:analysis / Q000097:blood / Q000627:therapeutic use; D002511:Cephalosporins / Q000032:analysis / Q000097:blood / Q000627:therapeutic use; D018450:Disease Progression; D015378:Imipenem / Q000032:analysis / Q000097:blood / Q000627:therapeutic use; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000098:blood supply / Q000737:chemistry / Q000473:pathology*; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D013845:Thienamycins / Q000032:analysis / Q000097:blood / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D013845:Thienamycins; D015378:Imipenem; D002439:Cefotaxime