Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis

Abstract

Background: Acute pancreatitis is a common acute abdominal emergency which lacks specific therapy. In severe attacks, areas of the pancreas may become necrotic. The mortality risk rises to >40% if sterile necrosis becomes superinfected, usually with gut derived aerobic organisms. Experimental and clinical studies indicate a window of opportunity of 1-2 weeks, when superinfection, and thus high-risk surgical debridement, may be prevented by administering systemic antibiotics to 'sterilise' tissues adjacent to necrotic areas. There are theoretical risks of encouraging antibacterial resistance and opportunistic fungal infections.

Objectives: To determine the effectiveness and safety of prophylactic antibiotic therapy in patients with severe acute pancreatitis who have developed pancreatic necrosis.

Search strategy: MEDLINE, EMBASE, and the Cochrane Library were searched. We also examined other sources including Conference Abstracts (published and unpublished data).

Selection criteria: Randomised controlled trials (RCT) were sought using the search strategy detailed below. No linguistic limitations were applied. RCTs were selected in which antibacterial therapy was evaluated in patients with severe acute pancreatitis associated with pancreatic necrosis proven by intravenous contrast-enhanced computed tomography (CT). No linguistic limitations were applied. Searching was undertaken initially in November 2001 and updated in March 2003.

Data collection and analysis: Two reviewers extracted data from trial publications independently, concerning rates for the primary end-points: with respect to: all cause mortality and rates of infection of pancreatic necrosis (proven by microbiological examination of fine needle aspirate or operative specimens). In addition, secondary end-points included peri-pancreatic sepsis, remote sepsis (respiratory, urinary, central venous line sources), operative rates, length of hospital stay, adverse events including the incidence of drug resistant microorganisms and opportunistic fungal infection.

Main results: It was possible to evaluate mortality in all four included studies, and it demonstrated a survival advantage for antibiotic therapy (Odds ratio 0.32, p=0.02). Pancreatic sepsis (infected necrosis) was also measurable in all four studies and showed an advantage for therapy (Odds ratio 0.51, p=0.04). Extra-pancreatic infection could be evaluated in three studies, but showed no significant advantage for therapy (Odds ratio 0.47, p=0.05).Operative treatment data was available in three studies, but surgery rates were not significantly reduced (Odds ratio 0.55, p=0.08). Fungal infections showed no strongly increased preponderance with therapy (Odds ratio 0.83, p=0.7), but there were no data on infection with resistant organisms. Length of hospital stay could only be evaluated in two studies and was not significantly different. Sub-group analyses planned for the influence on outcome measures of the antibiotic regimen, the time of commencement of therapy in relation to symptom onset and/or hospitalisation, duration of therapy, and aetiology could not be performed as no data were available.

Reviewer's conclusions: Despite variations in drug agent, case mix, duration of treatment and methodological quality (especially the lack of double blinded studies), there was strong evidence that intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk of superinfection of necrotic tissue and mortality in patients with severe acute pancreatitis with proven pancreatic necrosis at CT. Further studies are required to confirm all of the benefits suggested (in particular the need for operative debridement), to provide more adequate data on adverse effects, to address the choice of antibacterial agents and effects of varying duration of therapy, and whether outcome is related to aetiology.