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

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Abstract

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Background

Acute pancreatitis is a common abdominal emergency with no specific treatment. Pancreatic necrosis may complicate severe attacks, detectable by computed tomography (CT). Necrosis can become infected, making surgical intervention necessary and increasing mortality to more than 40%. Experimental studies suggest that antibiotic therapy may prevent infection, but could promote resistance and fungal infection.

Objectives

To determine the effectiveness and safety of prophylactic antibiotics in acute pancreatitis complicated by pancreatic necrosis.

Search methods

The Cochrane Library (Issue 1, 2006), MEDLINE (January 1966 ‐ December 2005), EMBASE (January 1980 ‐ December 2005) and CINAHL (January 1982 ‐ December 2005) were searched. We also examined Conference proceedings.

Selection criteria

Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis were sought using a detailed search strategy without linguistic limitation. RCTs. Initial searching was undertaken in November 2001. Latest update: December 2005.

Data collection and analysis

Two reviewers extracted data independently for rates of primary end‐points: mortality and pancreatic infection rates. Secondary end‐points included: non pancreatic infection and operative rates. Adverse events: antibiotic resistance and fungal infections. Subgroup analyses: antibiotic regimen.

Main results

Five evaluable studies randomised 294 patients. Analysis suggested significantly less mortality with therapy (6%) versus controls (15.3%), odds ratio 0.37 (95% CI 0.17, 0.83). Infected pancreatic necrosis rates were not significantly different (therapy 20%, controls 27.8%), odds ratio 0.62 (95% CI 0.35, 1.09), and neither were operative treatment rates or non‐pancreatic infection rates. Fungal infections were not significantly different at 4% with therapy versus 4.9% in controls, odds ratio 0.83 (95% CI 0.30, 2.27). There were no evaluable data on antibiotic resistance. Sub‐group analysis was performed for antibiotic regimen: beta lactam (192 patients), and quinolone plus imidazole (102 patients). With beta lactam prophylaxis there was significantly less mortality (6.3%) versus controls (16.7%), odds ratio 0.34 (95% CI 0.13, 0.91), and infected pancreatic necrosis (15.6%) versus (29.2%) in controls, odds ratio 0.41 (95% CI 0.20, 0.85), but there were no significant differences in operative treatment rates or non‐pancreatic infections. No significant differences were seen with quinolone plus imidazole.

Authors' conclusions

Antibiotic prophylaxis appeared to be associated with significantly decreased mortality but not infected pancreatic necrosis. Beta lactams were associated with significantly decreased mortality and infected pancreatic necrosis, but quinolone plus imidazole regimens were not. There were variations in methodological quality, treatment regimens, and a lack of data on adverse effects. Further better designed studies are needed to support antibiotic prophylaxis and, should these prove beneficial, to compare beta‐lactams with quinolones directly.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Antibiotics are sometime prescribed to prevent infection of dead tissue (pancreatic necrosis) in acute pancreatitis (a serious acute abdominal disease) because this complication carries a high risk of death. Their role is unproven.

Acute pancreatitis is a common life‐threatening disease which has no known treatment. Severe inflammation occurs in the pancreas, a digestive gland, and leads to abdominal pain and shock. In severe attacks, patients may develop pancreatic necrosis (gangrene), which can become infected by germs from nearby bowel. This usually requires major surgery and increases the risk of death to over 40%. Pancreatic necrosis can be identified by computed tomography (CT) scanning. Studies in experimental animals suggested that antibiotic treatment for several weeks may help prevent infection of the necrosis, which could reduce the risk of death. Such preventative treatment is referred to as prophylaxis. Randomised controlled trials (RCTs) have been carried out but have been inconclusive.

This meta‐analysis aimed to study whether antibiotic prophylaxis reduces the risks of death, and of infection of the pancreatic necrosis. It also looks into whether it diminishes the need for operations, whether it reduces infection outside the pancreas, and whether there are any adverse (side) effects of this treatment, such as resistant germs or fungal infection. The search for RCTs was restricted to those in which pancreatic necrosis was proven by CT. The medical literature and conference proceedings were searched and five RCTs met the selection criteria. They involved a total of 294 patients.

The quality of RCT varied. Only one RCT was doubly‐blinded (where neither patient nor investigators could know whether treatment or placebo was administered). There appeared to be benefit from antibiotic prophylaxis in reducing the risk of death, but not for the other criteria. There appeared to be no increased risk of fungal infections but there were insufficient data on antibiotic resistance. When the most common regimen (beta‐lactam antibiotics) was analysed from three studies, there was a significant reduction in risk of death, and risk of infected pancreatic necrosis. In the other regimen (quinolone plus imidazole) used in two studies, there were no significant differences for any of the criteria.

The conclusion that antibiotic prophylaxis may prevent death from acute pancreatitis, and with beta lactams only may also reduce infection of pancreatic necrosis and rates of operation, are difficult to support when the quality of RCTs and lack of data on adverse (side) effects are considered. Further better designed RCTs are needed to support antibiotic prophylaxis. One has recently concluded and is in analysis. This review will be revised as soon as the results from this study are published.