DOES PROPHYLACTIC ANTIBIOTIC THERAPY IMPROVE OUTCOMES IN SEVERE ACUTE PANCREATITIS: A CLINICAL DECISION MODEL

Abstract

Background: The prophylactic administration of antibiotics in subjects with severe acute pancreatitis (SAP) is a controversial subject. Although antibiotic administration may prevent infection in SAP it may also worsen outcomes by the creating of fungal superinfection. Prior studies have suffered from small sample size and missclassification bias. Aim: The goal of our study was to simulate a randomized clinical trial of prophylactic antibiotics versus placebo of up to one million patients with SAP. Methods: We modeled a randomized placebo controlled trial (RCT) of antibiotics versus placebo using the technique of decision analysis. We conducted a systematic review of the English published medical literature and obtained all articles on prophylactic antibiotic therapy in the management of acute pancreatitis. All point estimates and ranges of variable inputs for the model were derived from the published medical literature. We designed the model to provide input on three key parameters: 1. The length of administration of antibiotics, 2. The likelihood of developing fungal, bacterial or mixed infection and 3. Whether administration of prophylactic antibiotics was favorable vs. a no antibiotic strategy. Our base case consisted of a subject with SAP with or without necrosis. We tested the robustness of our model by using the technique of MonteCarlo simulation to simulate a series of randomized trials in which 100-1,000,000 patients were enrolled. Clinical endpoints were likelihood of death vs. life. Results: Our model demonstrated that the base case simulated RCT a short course of antibiotics (<14 days) was the preferred strategy. When we varied the model such that giving antibiotics was associated with a higher risk of fungal or bacterial infection no antibiotics was the preferred strategy. Monte-Carlo simulation for simulated trials of 100-1,000,000 patients demonstrated that short course of prophylactic antibiotics and fungal treatment was the preferred strategy 93% of the time. Conclusion: A short course of antibiotics appears to improve outcome in SAP. Consideration should be given to antifungal treatment as well.