Antibiotic prophylaxis: An ongoing controversy in the treatment of severe acute pancreatitis

The most significant change in the clinical course of acute pancreatitis over the past few decades has undoubtedly been the decrease in mortality. Overall mortality is now about 5%, and in the range of 10 20% for severe cases. The major improvements include intensive-care (IC) medicine, the accurate diagnosis of necrosis by CE-CT, the reliable diagnosis of infected necrosis by fine-needle aspiration (FNA), the ERCP concept in gallstone pancreatitis, late interventions in the case of infected necrosis, and new surgical techniques including postoperative continuous lavage. Almost all deaths caused by acute pancreatitis are observed in patients with severe acute pancreatitis. According to the Atlanta criteria, severe acute pancreatitis is defined as pancreatitis with local complications such as necrosis, abscess, hemorrhage, or pseudocysts, or systemic complications including systemic inflammatory response syndrome (SIRS), single or multiple organ failure (MFO), and sepsis. Early deaths during the initial phase of acute pancreatitis are caused by SIRS and MOF. Since more patients survive the first phase of severe acute pancreatitis, the prophylaxis and treatment of infected necrosis is of increasing clinical importance. Today there is no doubt that in necrotizing pancreatitis, pancreatic infection is the major risk factor for morbidity and mortality in the later phase of the disease [1 3]. Whereas pancreatic necrosis develops within the first week, superinfection of pancreatic and peripancreatic necrosis is usually observed 2 to 3 weeks after onset of the disease, and about 70% of patients with necrotizing pancreatitis develop infected necrosis by the third week [1,4]. In addition, the frequency of infection correlates with the extent of necrosis. The profile of organisms suggests an origin in the gastrointestinal tract. The ways in which microorganisms reach the pancreas include transperitoneal spread, spread along the pancreatic duct ascending from the duodenum or descending from the bile duct, as well as via lymph or the bloodstream. Attempts to decrease infection-related mortality in severe acute pancreatitis are focused on the prophylactic administration of antibiotics. Since the early 1970s several clinical trials have evaluated whether prophylactic antibiotic application could reduce the likelihood of pancreatic infection, development of sepsis, complications, and mortality in severe necrotizing pancreatitis. The early trials had several flaws, as the majority of patients evaluated had only mild disease so that pancreatic infection was very unlikely to develop. Moreover, the antibiotic agent applied in these first trials was ampicillin. However, we have demonstrated that the pancreas is highly impenetrable for antibiotics, and that most antibiotics, including ampicillin, do not reach sufficient tissue concentrations to inhibit the bacteria usually found in pancreatic infections [5]. The antibiotics with the greatest penetrance into the pancreatic tissue and with the best bactericidal properties are the carbapenems, followed by fluoroquinolones, and cephalosporins. Thus, all clinical trials performed since then have used these antibiotic agents. In addition, several randomized, controlled trials have compared the clinical efficiency of different antibiotics in the treatment of severe acute pancreatitis [6]. In a multicenter trial from Italy, 60 patients with severe necrotizing pancreatitis were randomly allocated to receive either intravenous pefloxacin, a fluoroquinalone with good pancreatic penetration and an appropriate spectrum of antimicrobiocidal activity, or