BACKGROUND: The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. 
DATA RESOURCES: All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. 
RESULTS: In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. 
CONCLUSION: Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients with severe acute pancreatitis.