Lorne H Blackbourne and Stephen M Cohn
Limiting prophylactic antibiotic use in severe pancreatitis minimizes the development of resistance and superinfections in vulnerable hosts, and also avoids unnecessary costs. Nearly three decades ago in small, prospective, randomized trials (totaling 192 patients), the use of antibiotics for routine pancreatitis was shown to be of no apparent benefit [9–11]. At this juncture there is no definitive, level one, data supporting the use of intravenous antibiotics in the treatment of patients with severe pancreatitis, even in the setting of pancreatic necrosis. The few prospective studies that exist investigating antibiotic use in severe pancreatitis have been nonblinded trials with small patient populations [1, 2].
Pederzoli and colleagues, in the most often quoted trial to support the routine use of antibiotics in pancreatitis, prospectively randomized 74 patients with severe necrotizing pancreatitis in a nonblinded fashion (secondary to either alcoholism or gallstones) to receive imipenem-cilastin or no antibiotics [1]. They found no significant differences in organ dysfunction or mortality (antibiotics, 29% and 7% versus no antibiotics, 39% and 12%; P = not significant) or mortality (antibiotics, 7% versus no antibiotics, 12%; P = not significant). The frequency of operation for debridement of pancreatic necrosis was also unaffected, but Pederzoli and colleagues did note that there was a decrease in the number of positive pancreatic cultures (percutaneously and intraoperatively).
Sainio and colleagues randomized 60 patients with alcoholic necrotizing pancreatitis to receive cefuroxime versus no antibiotic treatment in a nonblinded trial [2]. They reported a significant decrease in mortality in the patient group receiving antibiotics when compared with those not receiving antibiotics (3% versus 23%, P = 0.03). This study has been criticized because of its small size and because of the large percentage of patients (50%) who apparently succumbed from infections caused by Staphylococcus epidermidis (which were often associated with catheter sepsis).
Lutien and colleagues more recently used intravenous and enteral antibiotics (including amphotericin) to achieve decontamination of the gastrointestinal tract for the purpose of possibly decreasing bacterial inoculation of the necrotic pancreatic tissue via translocation [8]. One hundred and two patients were randomized to gut decontamination or to standard treatment. They reported a nonsignificant decrease in mortality (22% gut decontamination versus 35% controls, P = 0.19) in patients undergoing the antibiotic regimen. Other large trials utilizing gastrointestinal decontamination in groups of critically ill patients have failed to demonstrate a decrease in mortality or intensive care days. This extensive protocol, however, requires significant resource utilization and costs, and also carries a potential risk of the development of bacterial resistance.
While there is inconclusive data supporting the use of prophylactic antibiotics in the setting of severe pancreatitis, there is some evidence suggesting that misuse of antibiotics leads to devastating superinfections. Isenmann and colleagues have shown a significant increase in Candida infections in patients with pancreatic necrosis with prolonged exposure to antibiotics [12]. Among 92 patients with infected pancreatic necrosis, 22 had Candida infections and this subgroup had a major increase in mortality (64%) compared with those patients without Candida (19%, P < 0.01). Certainly, critically ill patients developing superinfections tend to be those with more severe disease, with longer antibiotic courses and with longer hospital stays.
We need to identify the subset of patients who are most likely to benefit from prophylactic antibiotics in the setting of severe pancreatitis. An adequately powered, randomized, double-blind, multicenter trial involving a suitable antibiotic regimen compared with placebo in a homogeneous group with severe pancreatitis is required. The primary endpoints should be clinically relevant, such as defined organ dysfunction, length of intensive care unit stay, and 30-day and 60-day mortality. Until such a study is completed, we cannot recommend routine prophylactic antibiotics in the setting of severe pancreatitis.
