Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis

Abstract

Introduction: 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.

Figure 1

Experimental design. Animals in all treatment groups received induction of acute necrotising pancreatitis at time point 0. In experimental group 1, animals were euthanased at 24 hours. Prophylactic antibiotic treatment (starting six hours after induction of pancreatitis) was evaluated versus no antibiotic treatment. In a second experimental group, animal were euthanased at 72 hours. Meropenem therapy on-demand (starting at 24 hours after induction of pancreatitis) was compared with prophylactic treatment and controls.

Figure 2

Bacterial superinfection at 24 hours. Meropenem given prophylactically reduced bacterial infection of blood, ascites, pancreas, and lymph nodes of the small bowel (LN Sm.bo.) and colon (LN Colon) 24 hours after induction of acute pancreatitis (*p = 0.015).

Figure 3

Survival rates at 24 and 72 hours. *p = 0.01 and ^#p = 0.05 compared with controls.

Figure 4

Bacterial superinfection at 72 hours. Both prophylactic and therapeutic antibiotic treatment reduced bacterial infection of blood, pancreatic tissue, mesenteric lymph nodes of small bowel (LN Sm.bo.) and colon (LN Colon). Compared with the control group without antibiotic treatment, prophylactic treatment reduced significantly bacterial infection of blood (p = 0.041), ascites (p = 0.039), pancreatic tissue (p < 0.001), mesenteric lymph nodes of small bowel (p = 0.010) and colon (p = 0.001). Compared with this, on-demand antibiotic treatment only reduced pancreatic superinfection and infection of mesenteric lymph nodes of the colon significantly (p = 0.026 and p = 0.039, respectively).