title: Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis.
abstract: BACKGROUND
  High morbidity and mortality rates in patients with severe acute pancreatitis are mainly caused by bacterial superinfection of pancreatic necrosis and subsequent sepsis. The benefit of early prophylactic antibiotics remains controversial because clinical studies performed to date were statistically underpowered. Thus, the aim of this study was to evaluate on-demand versus prophylactic antibiotic treatment in a standardised experimental model.
  
  
  METHODS
  Treatment groups received meropenem either therapeutically 24 hours after induction of necrotising pancreatitis or prophylactically before development of pancreatic superinfection. At 24 and 72 hours, pancreatic injury was investigated by histology and translocation by bacterial cultures of pancreatic tissue and mesenteric lymph nodes. Septic complications were evaluated by blood cultures and survival.
  
  
  RESULTS
  Without antibiotic treatment, pancreatic superinfection was observed in almost all cases after induction of necrotising pancreatitis. The 72-hour-mortality rate was 42.9% and bacterial infection of mesenteric lymph nodes and bacteraemia was found in 87.5% of the surviving animals. Therapeutic administration of meropenem on-demand reduced bacteraemia to 50% and mortality to 27.3%. However, prophylactic antibiotic treatment significantly reduced bacteraemia to 25.0% (p = 0.04) and pancreatic superinfection as well as mortality to 0% (p < 0.001 and p = 0.05, respectively) compared with controls.
  
  
  CONCLUSIONS
  In the present study both prophylactic and delayed antibiotic treatment on-demand reduced septic complications in a standardised setting of experimental necrotising pancreatitis. However, pancreatic superinfection, bacteraemia and mortality rates were reduced significantly by early treatment. Thus, in the absence of statistically relevant and well-designed clinical trials, the study demonstrates that prophylactic antibiotic treatment is superior to antibiotic treatment on-demand.
authors.affiliation: Department of General and Visceral Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. stefanfritz@gmx.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Fritz
authors.forename: Werner
authors.initials: W
authors.lastname: Hartwig
authors.forename: Ronny
authors.initials: R
authors.lastname: Lehmann
authors.forename: Katja
authors.initials: K
authors.lastname: Will-Schweiger
authors.forename: Mechthild
authors.initials: M
authors.lastname: Kommerell
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.forename: Lutz
authors.initials: L
authors.lastname: Schneider
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D001424:Bacterial Infections / Q000517:prevention & control; D008297:Male; D010195:Pancreatitis / Q000150:complications; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar; D015163:Superinfection / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents