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Routine administration of antibiotics in patients with AP is not currently recommended. In the past, prophylactic antibiotics were administered to decrease risk of infection in pancreatic necrosis. A few unblinded studies showed that imipenem was beneficial in preventing infection in pancreatic necrosis [45]. However, better‐conducted studies have shown that prophylactic antibiotics do not reduce risk of infection in necrotizing pancreatitis [46,47]. The AGA technical review observed that recent clinical trials showed no difference in risks of infected pancreatic and peripancreatic necrosis or mortality with prophylactic antibiotic usage [28]. Patients presenting with concomitant cholangitis or other coexisting infection should receive antibiotics in the emergency room. In all other patients, both mild and severe pancreatitis, routine antibiotic prophylaxis is not recommended [29].

In many instances, severe AP is indistinguishable from sepsis or concomitant cholangitis. In such scenarios when infection is suspected, antibiotics should be promptly administered after drawing blood sample for cultures. Once blood cultures are found to be negative, and no other source of infection is identified, antibiotics should be discontinued [5,29].