The role of surgery in the treatment of acute pancreatitis has clearly changed over the years. In the 1990s a clear reduction in hospital mortality was achieved through surgery, whereas the value of surgery (open, in general) has slipped into the background due to the improvement in intensive care medicine in general and the development of minimally invasive treatment options. Nowadays, patients with acute pancreatitis are only operated on after exhaustion of intensive medical care treatment and minimally invasive interventions or when complications occur that cannot be treated in any other way (e.g. hollow organ perforation). This article provides an overview of the currently used treatment measures.

Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis.

Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals.

The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy.

The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.

In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond.

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.

To assess the effects of different pharmacological interventions in people with acute pancreatitis.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.

We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.

Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.

We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.

seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.

Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines.

A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines.

Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles.

The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html.

This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using Epistemonikos) is an update of the summary published in August 2014, based on two systematic reviews appeared in January and February 2015. There is controversy about the effects of prophylactic antibiotics in acute pancreatitis. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified 18 systematic reviews including 19 randomised studies overall. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded that prophylactic antibiotics may reduce mortality and length of hospitalization in patients with acute pancreatitis, but the certainty of the evidence is low. The probability that future evidence change what we know is high.

Several studies have yielded conflicting results on the role of antibiotic prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta-analysis was carried out to investigate the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality.

Randomized controlled trials and cohort studies investigating impact of prophylactic systemic antibiotic used in acute necrotizing pancreatitis were retrieved from online databases. An overall analysis was done with all studies (Group 1), followed by subgroup analyses with randomized controlled trials (Group 2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality in each group using random effects model.

Eleven studies involving 864 patients were included. No significant differences in the incidence of infected pancreatic necrosis were observed with prophylactic antibiotic use in all groups. Prophylactic antibiotic use was not associated with significant differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p = 0.04). There was no statistical difference in the incidence of fungal infections and surgical interventions.

Antibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

Acute pancreatitis is a common cause of hospitalization and a major source of morbidity worldwide. When it is severe, and especially when it progresses to include necrosis of the pancreas, the risk of infection rises and mortality increases. Early reports suggested prophylactic antibiotics given in severe pancreatitis prevent infection and death. More recent clinical trials do not support this benefit, and meta-analyses on the topic offer conflicting recommendations. In this article, we evaluate the body of published literature examining the use of antibiotics as a preventive measure in acute pancreatitis. The highest quality, currently available data fail to support prophylactic use of antibiotics, which should be added to treatment regimens only where infection has been proven.

Our understanding of the role of antibiotics in the management of patients with pancreatic necrosis has changed over the past 5 years. Initial studies suggested that antibiotics were useful in preventing infection of necrosis, septic complications, and mortality in patients with acute pancreatitis; however, more recent, better-designed studies established that prophylactic antibiotics are not helpful. In the absence of infection, sterile necrosis is treated conservatively. With insufficient evidence to recommend antibiotics, these agents should be reserved to treat established infection of pancreatic necrosis. Infected necrosis is treated by targeting microbes with pancreatic-penetrating antibiotics (eg, carbapenems, quinolones in combination with metronidazole, or high-dose cephalosporins). If the patient with infected necrosis remains septic or deteriorates, surgical intervention should be performed urgently. Stable patients with infected necrosis can be managed more conservatively in a closely monitored environment. Recent studies suggest that many patients can clear the infection with antibiotics, but even if they do not clear the infection, delay in surgery decreases the mortality rate. Delaying surgery by using antibiotics may allow use of less invasive procedures if drainage is needed. The timing and method of interventions must be individualized based on the patient's condition, anatomic complications, patient's preference after informed consent, and expertise available at the institution.

The incidence of acute pancreatitis varies from 5 to 80 per 100,000 throughout the world. The most common cause of death in these patients is infection of pancreatic necrosis by enteric bacteria, spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. In order to provide evidence of the effect of antibiotic prophylaxis in severe acute pancreatitis (SAP) we performed an updated systematic review and meta-analysis on this topic.

The review of randomized controlled trials was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. We conducted a search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. For assessment of the treatment effects we calculated the risk ratios (RRs) for dichotomous data of included studies.

Fourteen trials were included with a total of 841 patients. The use of antibiotic prophylaxis was not associated with a statistically significant reduction in mortality (RR 0.74 [95% CI 0.50-1.07]), in the incidence of infected pancreatic necrosis (RR 0.78 [95% CI 0.60-1.02]), in the incidence of non-pancreatic infections (RR 0.70 [95% CI 0.46-1.06]), and in surgical interventions (RR 0.93 [95% CI 0.72-1.20]).

In summary, to date there is no evidence that supports the routine use of antibiotic prophylaxis in patients with SAP.

Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection.

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

Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched.

Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis.

Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem).

Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84).

No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.

Our knowledge of acute pancreatitis is still far from complete and there is no unanimous agreement concerning the pathophysiological processes leading to typical alterations during the course of acute pancreatitis. We reviewed the paper published in the last decade on the pathophysiology and treatment of acute pancreatitis. It is difficult to translate the experimental therapeutic results into clinical practice. For example, lexipafant was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on severe acute pancreatitis in humans. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of designing clinical studies capable of giving reliable statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings. Thus, analgesia, supportive care, and treatment of the pulmonary and renal complications remain the cornerstones of the treatment of acute pancreatitis, especially in the severe form of the disease.

Patients who have been diagnosed as having acute pancreatitis should be, on principle, hospitalized. Crucial fundamental management is required soon after a diagnosis of acute pancreatitis has been made and includes monitoring of the conscious state, the respiratory and cardiovascular system, the urinary output, adequate fluid replacement and pain control. Along with such management, etiologic diagnosis and severity assessment should be conducted. Patients with a diagnosis of severe acute pancreatitis should be transferred to a medical facility where intensive respiratory and cardiovascular management as well as interventional treatment, blood purification therapy and nutritional support are available. The disease condition in acute pancreatitis changes every moment and even symptoms that are mild at the time of diagnosis may become severe later. Therefore, severity assessment should be conducted repeatedly at least within 48 h following diagnosis. An adequate dose of fluid replacement is essential to stabilize cardiovascular dynamics and the dose should be adjusted while assessing circulatory dynamics constantly. A large dose of fluid replacement is usually required in patients with severe acute pancreatitis. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with severe acute pancreatitis. Although the efficacy of intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional continuous regional arterial infusion and blood purification therapy.

Mild acute pancreatitis (AP) is rarely complicated by infection, and the value of prophylactic antibiotics is questionable. We report a case of mild AP complicated by infection, which developed within 1 week after the onset. A 66-year-old woman was referred to our hospital where a diagnosis of mild AP was made, based on laboratory data and computed tomography (CT) findings. She was managed conservatively with fluid resuscitation, intravenous antibiotics, and protease inhibitor. Her general condition improved initially, but a high fever redeveloped on hospital day 3. On hospital day 7, a repeat CT scan showed a peripancreatic fluid collection with gas, indicating peripancreatic abscess. A drainage operation was performed, and the organism cultured from the abscess was Escherichia coli. Her postoperative course was uneventful. We report this case to stress that infection may develop even in mild AP, and even in the early phase.

Infected pancreatic necrosis (IPN) is one of the main causes of mortality in patients with acute pancreatitis (AP). The choice of antibiotic therapy in AP should be based on penetration of the drug in the pancreas and the degree of coverage provided against the typical bacterial flora produced in IPN. Drugs such as imipenem, ciprofloxacin and metronidazole have been widely studied and seem to be ideal in the treatment of INP. Clinical practice guidelines recommend a carbapenem agent as the initial empirical treatment. When Gram-positive pathogens are isolated in pancreatic samples, vancomycin can be used alone or associated with a carbapenem. Currently, prophylactic antibiotic therapy for IPN is not supported by the scientific evidence, since both the best quality studies (double-blind) and the latest meta-analysis published have found no benefit of the use of this strategy.

The management of infected peripancreatic or pancreatic necrosis in patients with severe pancreatitis has changed considerably in recent years. This review discusses the recent literature on prevention, detection, and management of infected necrosis. Though antibiotics, probiotics, and enteral nutrition have been tried to prevent infected necrosis, only enteral nutrition has consistently proven to be effective. Antibiotics and probiotics have not shown a consistent beneficial effect on outcome. Enteral nutrition reduced infectious complications and mortality in severe pancreatitis, compared with parenteral nutrition. The detection of infection of pancreatic necrosis is important for clinical decision making. Fine-needle aspiration may be used to confirm suspected infection, but if its results will not change clinical decisions, it should be omitted, as it may even introduce infection. Minimally invasive surgical, radiologic, or endoscopic intervention is increasingly being applied. In the absence of level 1 evidence, local expertise dictates which type of intervention is applied.

The effect of prophylactic antibiotic treatment on infection and survival of acute necrotizing pancreatitis (ANP) remains uncertain. The aim of this study was to assess the long-term efficacy of prophylactic antibiotic treatment for ANP.

Searches were carried out of electronic databases including Medline, EMBASE, the Cochrane Controlled Trials Register, the Science Citation Index, and PubMed (updated to December 2007), and manual bibliographical searches were also conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing prophylactic antibiotic treatment with placebo or no treatment was performed.

Eight RCTs including 540 patients were assessed. The outcomes included infected necrosis, death, non-pancreatic infection, surgical intervention, and length of hospital stay. Prophylactic antibiotic use leads to a significant reduction of infected necrosis (relative risk (RR) 0.69, 95% CI, 0.50-0.95; p=0.02), non-pancreatic infections (RR 0.66 95% CI, 0.48-0.91; p=0.01), and length of hospital stay (p=0.004) but was not associated with a statistically significant reduction in mortality (RR 0.76 95% CI, 0.50-1.18; p=0.22) and surgical intervention (RR 0.90 95% CI, 0.66-1.23; p=0.52). In a subgroup analysis, carbapenem was associated with a significant reduction in infected necrosis (p=0.009) and non-pancreatic infections (p=0.006), whereas other antibiotics were not.

Prophylactic antibiotic treatment is associated with a significant reduction of pancreatic or peripancreatic infection, non-pancreatic infection, and length of hospital stay, but cannot prevent death and surgical intervention in acute necrotizing pancreatitis.

There is no agreement whether intravenous prophylactic antibiotics can reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis (ANP). We performed a meta-analysis comparing intravenous antibiotics with placebo or no treatment in randomized controlled trials (RCTs).

Databases including MEDLINE, EMBASE, the Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were infected necrosis and mortality.

Seven trials involving 467 patients were included. Analysis suggested infected pancreatic necrosis rates were not significantly different (antibiotics 17.8%, controls 22.9%), RR 0.81 (95% CI 0.54-1.22). There was nonsignificantly decreased mortality with antibiotics (9.3%) versus controls (15.2%), RR 0.70 (95% CI 0.42-1.17). Subsequent subgroup analysis confirmed antibiotics were not statistically superior to controls in reduction of infected necrosis and mortality.

Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in patients with ANP.

In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved.

A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe.

One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo.

Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days.

Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization.

Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476).

This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.

The main causes of death in severe pancreatitis are multiorgan failure and septic complications. Prophylactic treatment with effective antibiotics is therefore a tempting therapeutic option. However, there could be side effects such as selection of resistant microbes and fungi. The aim of the present study was to compare the rate of infectious complications, interventions, days in the intensive care unit (ICU), morbidity and mortality in patients with severe pancreatitis randomized to prophylactic therapy with imipenem compared with those receiving no treatment at all.

Seventy-three patients with severe pancreatitis were included in a prospective, randomized, clinical study in seven Norwegian hospitals. The number of patients was limited to 73 because of slow patient accrual. Severe pancreatitis was defined as a C-reactive protein (CRP) level of >120 mg/l after 24 h or CRP >200 48 h after the start of symptoms. The patients were randomized to either early antibiotic treatment (imipenem 0.5 g x 3 for 5-7 days) (imipenem group) (n=36) or no antibiotics (control group) (n=37).

The groups were similar in age, cause of pancreatitis, duration of symptoms and APACHE II score. Patients in the imipenem group experienced lower rates of complications (12 versus 22 patients) (p=0.035) and infections (5 versus 16 patients) (p=0.009) than those in the control group. There was no difference in length of hospital stay (18 versus 22 days), need of intensive care (8 versus 7 patients), need of acute interventions (10 versus 13), nor for surgery (3 versus 3) or 30-day mortality rates (3 versus 4).

The study, although underpowered, supports the use of early prophylactic treatment with imipenem in order to reduce the rate of septic complications in patients with severe pancreatitis.

The clinical course in acute necrotizing pancreatitis is mainly determined by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic regimens for early and late treatment was investigated in the taurocholate model of necrotizing pancreatitis in the rat.

Seventy male Wistar rats were divided into five pancreatitis groups (12 animals each) and a sham-operated group (10 animals). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals received two different antibiotic regimes (20 mg/kg imipenem or 20 mg/kg ciprofloxacin plus 20 mg/kg metronidazole) early at 2, 12, 20, and 28 h after induction of pancreatitis or late at 16 and 24 h after induction of pancreatitis or no antibiotics (control). Animals were examined after 30 h for pancreatic and extrapancreatic infection.

Early and late antibiotic treatment with both regimes could significantly reduce pancreatic infection from 58 to 8-25%. However, extrapancreatic infection was only reduced by early antibiotic therapy. While quinolones also reduced bacterial counts in small and large bowel, imipenem did not.

In our animal model of necrotizing pancreatitis, early and late treatment with ciprofloxacin/metronidazole and imipenem reduce bacterial infection of the pancreas. Extrapancreatic infection, however, is reduced significantly only by early antibiotic treatment. The effectivity of early antibiotic treatment in the clinical setting should be subject to further investigation with improved study design and sufficient patient numbers.

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.

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

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.

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.

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.

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.

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.

Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis.

A meta-analysis of randomized controlled trials was carried out. Medline, Web of Science, the Cochrane controlled trials register and international conference proceedings were searched, with a citation review of relevant primary and review articles.

Six of 328 studies assessed were included in data extraction. Primary outcome measures were infected necrosis and death. Secondary outcome measures were non-pancreatic infections, surgical intervention and length of hospital stay. Prophylactic antibiotic use was not associated with a statistically significant reduction in infected necrosis (relative risk (RR) 0.77 (95 per cent confidence interval (c.i.) 0.54 to 1.12); P = 0.173), mortality (RR 0.78 (95 per cent c.i. 0.44 to 1.39); P = 0.404), non-pancreatic infections (RR 0.71 (95 per cent c.i. 0.32 to 1.58); P = 0.402) and surgical intervention (RR 0.78 (95 per cent c.i. 0.55 to 1.11); P = 0.167). It was, however, associated with a statistically significant reduction in hospital stay (P = 0.040).

Prophylactic antibiotics do not prevent infected necrosis or death in acute necrotizing pancreatitis.

The basic principles of the initial management of acute pancreatitis are adequate monitoring of vital signs, fluid replacement, correction of any electrolyte imbalance, nutritional support, and the prevention of local and systemic complications. Patients with severe acute pancreatitis should be transferred to a medical facility where adequate monitoring and intensive medical care are available. Strict cardiovascular and respiratory monitoring is mandatory for maintaining the cardiopulmonary system in patients with severe acute pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular system. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with necrotizing pancreatitis. Although the efficacy of the intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional measures, blood purification therapy and continuous regional arterial infusion of a protease inhibitor and antibiotics, depending on the patient's condition.

Infectious complications are the most common cause of morbidity and mortality in patients suffering from severe acute pancreatitis. Approximately 25% of patients develop pancreatic necrosis. In these patients with severe disease complicated by necrosis, there is evidence that preventing infection of the pancreatic necrosis decreases morbidity and mortality. Whereas sterile necrosis is often treated conservatively, surgical debridement is required when the necrosis becomes infected. Although surgery is necessary in patients with infected necrosis, for a variety of reasons surgical intervention increases the morbidity and mortality of the disease. Preventing infectious complications, such as infected necrosis, through the use of prophylactic antibiotics is controversial. Despite reviewing the same evidence, different authors and organizations have formed different conclusions. In this review, we perform a critical analysis of the studies. Overall, the use of antibiotics in patients with necrotizing pancreatitis appears to decrease infectious complications and mortality.

Acute pancreatitis is an inflammatory disorder, but it is not generally caused by infectious agents. Yet, in tertiary referral hospitals, the majority of patients who die of necrotizing pancreatitis do so as a consequence of infectious complications. These generally develop late (2-4 weeks) in the disease process. This finding prompted the hypothesis that infectious pancreatitis complications, such as an abscess or an infected necrosis which can lead to death, can be reduced by treating patients who suffer, at least initially, from a sterile inflammatory disorder, with broad-spectrum antibiotics. Here we review the experimental foundations of this hypothesis, as well as the difficulties that were encountered when clinical trials were undertaken to confirm it. At present, there is still a case for treating necrotizing pancreatitis patients with broad-spectrum antibiotics (specifically carbapenems), but the extent of the beneficial effect and the number of patients expected to profit from this approach should not be overestimated.

Acute pancreatitis is a disease of increasing prevalence, unchanged mortality over many decades, and limited treatment strategies. Progress has been made in developing therapies that reduce the rate of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatitis and in preventing infected pancreatic necrosis with intravenous carbapenems. Attempts at reducing pancreatic enzyme output or inhibiting the activity of digestive enzyme proteases have not yielded encouraging results - nor have anti-inflammatory strategies for the treatment of acute pancreatitis been found to be effective so far. Future therapeutic options that are presently being developed or under investigation attempt to restore pancreatic secretory function, interfere with inflammatory pathways in a more effective manner, or inhibit digestive enzyme proteases more selectively.

To carry out a meta-analysis of published studies in order to evaluate the clinical efficacy of prophylactic antibiotics in severe acute pancreatitis (SAP).

MEDLINE, China Biological Medicine, Embase and Cochrane Data Base for Systematic Reviews were searched for randomized controlled trials on the efficacy of prophylactic antibiotics in patients with SAP from 1966 to 2004. Six studies met our inclusion criteria. Two authors (G.S.X. and Z.H.W.) independently extracted the following data from these studies: trial design, characteristics of participants and outcomes. Data were analyzed by Revman 4.2 software.

In patients with SAP, prophylactic antibiotics, including broad-spectrum antibiotics that usually achieve therapeutic pancreatic tissue levels, did not reduce pancreatic infection (relative risk, RR, 0.77, 95% confidence interval 0.48-1.24, p = 0.28), surgical intervention (RR 0.84, 95% confidence interval 0.40-1.74, p = 0.64) and mortality rate (RR 0.54, 95% confidence interval 0.28-1.04, p = 0.07).

Prophylactic antibiotic administration is not an appropriate treatment strategy in patients with SAP, it should be limited in patients with pancreatic necrosis, as demonstrated by computerized tomography.

The treatment of severe acute pancreatitis has been evolving from routine operative management to nonoperative care for patients without evidence of pancreatic infection.

Retrospective chart review of patients with severe acute pancreatitis at a single institution during a 9-year period.

Sixty consecutive patients had severe pancreatitis. Forty-two had pancreatic necrosis on computed axial tomography (13 infected and 29 sterile). Patients with infected necrosis and 8 with sterile necrosis had operative debridement; the remaining patients were managed without operation (n = 39). The overall mortality was 15%. Mortality was directly related to the Acute Physiology and Chronic Health Examination II and Marshall organ failure scores (P <0.001). Patients who died had a greater incidence of nosocomial infection.

Patients with infected pancreatic necrosis require early operative debridement, whereas those with sterile necrosis or severe pancreatitis without necrosis can usually be managed safely without surgery.

Acute pancreatitis represents a spectrum of disease ranging from a mild, self-limited course requiring only brief hospitalization to a rapidly progressive, fulminant illness resulting in the multiple organ dysfunction syndrome (MODS), with or without accompanying sepsis. The goal of this consensus statement is to provide recommendations regarding the management of the critically ill patient with severe acute pancreatitis (SAP).

An international consensus conference was held in April 2004 to develop recommendations for the management of the critically ill patient with SAP. Evidence-based recommendations were developed by a jury of ten persons representing surgery, internal medicine, and critical care after conferring with experts and reviewing the pertinent literature to address specific questions concerning the management of patients with severe acute pancreatitis.

There were a total of 23 recommendations developed to provide guidance to critical care clinicians caring for the patient with SAP. Topics addressed were as follows. 1) When should the patient admitted with acute pancreatitis be monitored in an ICU or stepdown unit? 2) Should patients with severe acute pancreatitis receive prophylactic antibiotics? 3) What is the optimal mode and timing of nutritional support for the patient with SAP? 4) What are the indications for surgery in acute pancreatitis, what is the optimal timing for intervention, and what are the roles for less invasive approaches including percutaneous drainage and laparoscopy? 5) Under what circumstances should patients with gallstone pancreatitis undergo interventions for clearance of the bile duct? 6) Is there a role for therapy targeting the inflammatory response in the patient with SAP? Some of the recommendations included a recommendation against the routine use of prophylactic systemic antibacterial or antifungal agents in patients with necrotizing pancreatitis. The jury also recommended against pancreatic debridement or drainage for sterile necrosis, limiting debridement or drainage to those with infected pancreatic necrosis and/or abscess confirmed by radiologic evidence of gas or results or fine needle aspirate. Furthermore, the jury recommended that whenever possible, operative necrosectomy and/or drainage be delayed at least 2-3 wk to allow for demarcation of the necrotic pancreas.

This consensus statement provides 23 different recommendations concerning the management of patients with SAP. These recommendations differ in several ways from previous recommendations because of the release of recent data concerning the management of these patients and also because of the focus on the critically ill patient. There are a number of important questions that could not be answered using an evidence-based approach, and areas in need of further research were identified.

Infected pancreatic necrosis is the leading cause of death in patients with severe acute pancreatitis. Early prophylactic antibiotic treatment is effective in preventing conversion of sterile necrosis to pancreatic infection, but its effect on mortality remains unproven. Fungal infections may predict a worse outcome, but no evidence supports the use of antifungal prophylaxis. Because infection of pancreatic necrosis by enteric bacteria can develop despite prophylaxis, a high index of suspicion should allow early detection followed by aggressive management.

Although most patients with acute pancreatitis have a mild course, almost a quarter of patients will develop complications. It has become clear that the early management of patients with acute pancreatitis will likely affect outcome. Too often patients are admitted to the hospital with what appears to be mild disease only later to deteriorate with severe disease. This review will focus on the early management of patients with acute pancreatitis in an attempt to prevent severe disease, complications, and death.

The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows.

A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed.

Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur.

Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.

While interstitial acute pancreatitis usually takes a benign course, necrotizing acute pancreatitis takes a severe course, mainly because of severe local and systemic complications. After a quick diagnosis it is necessary to rapidly assess a degree of severity of the disease and thus the prognosis. The clinical picture and the result of imaging procedures do not always correspond. The management basically includes to treat pain as well as to administer fluid, electrolyte, protein and calories. In addition, systemic treatment of complications such as shock or respiratory and renal insufficiency--if occurring--is necessary. In case of pancreatic necrosis, prophylactic administration of pancreas-penetrable antibiotics is recommended to avoid infection. In the severely ill with infected pancreatic necrosis, surgery is the treatment of choice. In approximately 10% of all patients with alcohol-induced pancreatitis, there is a gradual transition to chronic pancreatitis.

In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

Pancreatitis is not an infrequent diagnosis in patients admitted to the intensive care unit. Prolonged stays, intense resource utilization and high morbidity/mortality are commonplace in such patients. Management for the most part is supportive, with the surgical team keeping close watch to intervene as the need arises. Over the past few decades there has been considerable debate regarding the usefulness of systemic antibiotics to prevent infectious complications in patients with evidence of pancreatic necrosis. In the present article of Critical Care, two expert groups debate the two sides of this contentious antibiotic issue.

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.

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

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

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.

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.

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.

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.

The clinical significance and incidence of the specific pancreatic infections during severe pancreatitis, such as infected pancreatic necrosis and pancreatic abscesses, is very well known in the literature. The up-to-date knowledge in both the microbiological and pharmacological field related to pancreatitis suggests a series of antibiotics which are potentially useful in the prophylaxis of pancreatic infections. Here we review the most important controlled clinical experiences reported up to now.