Strategy of antibiotic therapy in SAP,De-escalate (cefoperazone+metronidazole) or Escalate (meropenem) therapy,which one is better.

SAP is a serious and life-threatening disease and requires intensive and aggressive management of multiple organ failure and severe infectious complications that can develop in these patients. The most common cause of death in patients suffering from severe acute pancreatitis (SAP) is the infection of pancreatic necrosis by enteric bacteria with mortality rates of 30% (range 14- 62%),spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. Pancreatic infections are more often monomicrobial, especially E. coli in the two first weeks (100% and 62.5%) of onset, with a shift from gram-negative to gram-positive as the pancreatitis progressed.

In order to evaluate the benefit of prophylactic antibiotic application, a number of randomized controlled clinical trials have been published over the past 15 years. Since the results were conflicting and most studies were of low methodological quality and/or statistically underpowered, meta-analyses have been performed to assess this important issue. However, their results ranged from absolutely no effect of antibiotic prophylaxis to positive effects regarding mortality, the incidence of infected pancreatic necrosis and the incidence of extra pancreatic infections.

In order to provide reliable evidence of the effect of antibiotherapy strategy in SAP, we performed a prospective randomized multicenter clinical trial.

Inclusion Criteria:

• severe Acute Pancreatitis according to Atlanta criteria revisited in 2012

Exclusion Criteria:

• concurrent sepsis or (peri)pancreatic infection caused by a second disease
• patients with chronic organ failure (chronic renal failure needs kidney replacement, chronic heart failure, decompensate hepatic cirrhosis, chronic obstructive pulmonary disease)
• recurrent or endoscopic retrograde cholangiopancreatography (ERCP), or traumatic or operative pancreatitis
• pregnancy, malignancy or immunodeficiency
• a history of allergy to meropenem, cefoperazone and metronidazole
• a history of antibiotic administration within 48 h prior to enrollment
• possible death within 48 h after enrollment