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.

Necrotizing pancreatitis is a life-threatening presentation of acute pancreatitis. The mortality of 20-80% initially depends on the persistence of organ failure and systemic inflammatory response syndrome (SIRS) and, in the later course of the disease, on secondary infection of the necrosis. The questions whether prophylactic antibiotics aiming to prevent this infection should be administered and which antibiotic is the best to use, as well as the problem of fungal infection under antibiotic treatment are still intriguing and insufficiently solved.

A search of the literature using PubMed was carried out, supplemented by a review of the programmes of the Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW).

Despite the widely practised prophylactic antibiotic administration in severe pancreatitis, no evidence for the benefit of this strategy exists. One of the drawbacks might be a tendency for disastrous fungal infection under prophylactic antibiotics. Bacterial translocation from the gut in the second week after the onset of symptoms is the major source for infection of pancreatic necrosis and provides a clear indication for antibiotic treatment. However, routine fine-needle aspiration for a calculated antibiotic therapy cannot be recommended, and all other tests offer only indirect signs. Important factors such as enteral versus parenteral feeding and the method of necrosectomy are mostly neglected in the trials but seem to be essential for the outcome of the patient.

Even though most meta-analyses including the newer double-blind, placebo-controlled trials on prophylactic antibiotics showed no beneficial effects in the prevention of infection of necrosis and/or outcome of the patients, this strategy is still widely used in clinical routine. Since nearly all trials published so far show systematic problems (i.e. inaccurate definition of the severity of the disease, poor statistical testing, and neglect of differences in the route of nutrition), there is a need for randomized controlled prospective trials with exact definitions of the disease.

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.

Acute necrotizing pancreatitis is a severe acute inflammatory disease of the pancreas that can lead to extrapancreatic organ involvement. Supervening lung injury is an important clinical entity determining the prognosis of the patient. Probiotics are dietary supplements known to reduce or alter inflammation and inflammatory cytokines. In the present study, we hypothesize that probiotics may reduce lung injury by reducing bacterial translocation, which results in reduced infection, inflammation, and generation of proinflammatory cytokines in an experimental model of acute necrotizing pancreatitis.

Pancreatitis was induced by concomitant intravenous infusion of cerulein and glycodeoxycholic acid infusion into the biliopancreatic duct. Saccharomyces boulardii was used as the probiotic agent. Rats were divided into three groups: sham, pancreatitis-saline, which received saline via gavage at 6 and 24 h following the pancreatitis, pancreatitis-probiotics, which received probiotics via gavage method at 6 and 24 h following the pancreatitis. The rats were sacrificed at 48 h, venous blood, mesenteric lymph node, pancreatic and lung tissue samples were obtained for analysis.

Serum pancreatic amylase, lactate dehydrogenase, secretory phospholipase A(2), and IL-6 were found to be increased in pancreatitis-saline group compared with the other groups (P < 0.05). Histological analyses revealed that edema, inflammation, and vacuolization as well as polymorphonuclear leukocyte infiltration in the lung tissue was significantly reduced in the probiotic treated group. Bacterial translocation was significantly reduced in the probiotic treated group compared with the other groups (P < 0.05).

These results suggest that Saccharomyces boulardii reduce the bacterial translocation. As a result of this, reduced proinflammatory cytokines and systemic inflammatory response was observed, which may be the reason underlying reduced lung injury in acute necrotizing pancreatitis.

Acute pancreatitis has an incidence of about 300 per 1 million individuals per year, of which 10-15% of patients develop the severe form of the disease. Novel management options, which have the potential to improve outcome, include initial proper fluid resuscitation, which maintains microcirculation and thereby potentially decreases ischaemia and reperfusion injury. The traditional treatment concept in acute pancreatitis, fasting and parenteral nutrition, has been challenged and early initiation of enteral feeding in severe pancreatitis and oral intake in mild acute pancreatitis is both feasible and provides some benefits. There are at present no data supporting immunonutritional supplements and probiotics should be avoided in patients with acute pancreatitis. There is also no evidence of any benefits provided by prophylactic antibacterials in patients with predicted severe acute pancreatitis. A variety of specific medical interventions have been investigated (e.g. intense blood glucose monitoring by insulin) but none has become clinically useful. Lessons can probably be learned from critical care in general, but studies are needed to verify these interventions in acute pancreatitis.

The time-related metabolic responses to l-arginine (ARG)-induced exocrine pancreatic toxicity were investigated using single ip doses of 1,000 and 4,000 mg/kg body weight over a 7 day experimental period in male Sprague-Dawley rats. Sequential timed urine and plasma samples were analyzed using high resolution (1)H NMR spectroscopy together with complementary clinical chemistry and histopathology analyses. Principal components analysis (PCA) and orthogonal projection on latent structures discriminant analysis (O-PLS-DA) were utilized to analyze the (1)H NMR data and to extract and identify candidate biomarkers and to construct metabolic trajectories post ARG administration. Low doses of ARG resulted in virtually no histopathological damage and distinct reversible metabolic response trajectories. High doses of ARG caused pancreatic acinar degeneration and necrosis and characteristic metabolic trajectory profiles with several distinct phases. The initial trajectory phase (0-8 h) involved changes in the urea cycle and transamination indicating a homeostatic response to detoxify excess ammonia generated from ARG catabolism. By 48 h, there was a notable enhancement of the excretion of the gut microbial metabolites, phenylacetylglycine (PAG), 4-cresol-glucuronide and 4-cresol-sulfate, suggesting that compromised pancreatic function impacts on the activity of the gut microbiota giving potential rise to a novel class of surrogate extragenomic biomarkers of pancreatic injury. The implied compromise of microbiotal function may also contribute to secondary hepatic and pancreatic toxic responses. We show here for the first time the value of metabonomic studies in investigating metabolic disruption due to experimental pancreatitis. The variety of observed systemic responses suggests that this approach may be of general value in the assessment of other animal models or human pancreatitis.

Multi-organ dysfunction, and in particular lung injury, is often responsible for the unfavorable outcome of patients with severe acute pancreatitis. Understanding of the mechanisms by which local inflammation in the pancreas leads to end-organ injury is crucial for the development of new therapeutic strategies.

A MEDLINE search was performed with the terms "acute pancreatitis," "lung injury," "inflammatory response," "SIRS," and "multi-organ dysfunction." Pertinent articles were selected for analysis.

Modulation of the inflammatory response using a combination of immunomodulatory agents may decrease the incidence of severe pancreatitis-related acute lung injury and acute respiratory distress syndrome.

Clinical trials are of utmost importance to establish the validity of such strategies.

Fine-needle aspiration (FNA) is the procedure of choice for accurate diagnosis of infected necrosis. However, invasive procedures increase the risk of secondary pancreatic infection and the timing of FNA is still a matter for debate. Our objective was to assess the value of routine clinical tests to determine the minimal risk for infected necrosis, thereby optimizing timing and selection of patients for image-guided FNA.

This prospective, non-randomized study comprised 90 patients with acute necrotizing pancreatitis. The data of 52 patients were used for discriminant function analysis to determine the differences between patients with infected necrosis and those with sterile necrosis. Cut-off points for variables were established using receiver operating characteristic (ROC) curve analysis and logistic regression was performed to determine the risk of infected necrosis. The clinical relevance of the defined diagnostic system was prospectively tested in a further 38 consecutive patients with acute necrotizing pancreatitis (ANP).

Discriminant function analysis showed that C-reactive protein (CRP) and white blood cell (WBC) values were significant discriminators between patients with sterile necrosis and those with infected necrosis. Cut-off values of 81 mg/l for CRP and 13 x 10(9)/l for WBC were established. The predicted risk for infected necrosis is approx. 1.4% if both tests are below the defined cut-off values. Consequently, we found FNA unnecessary in this subset of patients, unless otherwise indicated, as this invasive procedure per se carries a certain risk of bacterial contamination.

Routine clinical tests are helpful in diagnosing the development of infected necrosis. Based on the application of classification functions, the timing and selection of patients for image-guided FNA can be optimized.

Acute pancreatitis (AP) is a common disease that has a mild to moderate course in most cases. During the last decade, a change in diagnostic facilities as well as improved intensive care have influenced both morbidity and mortality in AP. Still, however, a number of controversies and unresolved questions remain regarding AP. These include prognostic factors and how these may be used to improve outcome, diagnostic possibilities, their indications and optimal timing, and the systemic inflammatory reaction (systemic inflammatory response syndrome--SIRS) and its effect on the concomitant course of the disease and potential development of organ failure. The role of the gut has been suggested to be important in severe AP, but has recently been somewhat questioned. Despite extensive research, pharmacological and medical intervention of proven clinical value is scarce. Various aspects on surgical interventions, including endoscopic sphincterotomy, cholecystectomy and necrosectomy, as regards indications and timing, will be reviewed. Last, but not least, are the management of late complications and long-term outcome for patients with especially severe AP.

We compared two imipenem regimens for prevention of septic complications in patients with severe acute necrotizing pancreatitis (ANP).

Prospective, randomized open clinical trial involving intensive care units of 14 Spanish Hospitals.

92 patients with ANP.

Imipenem/cilastatin was administered at 500 mg four times daily starting at the time of diagnosis of ANP, within the first 96 h from the onset of symptoms. Patients were randomized to receive antibiotic prophylaxis either for 14 days (group 1) or at least for 14 days and as long as major systemic complications of the disease persisted (group 2).

Antibiotic was maintained in group 2 for 19.7+/-10.9 days. The incidence of infected pancreatic necrosis, pancreatic abscess, and extrapancreatic infections was 11%, 17%, and 28% in group 1 and 17.4%, 13%, and 35% in group 2 (n.s.). Pancreatic or extrapancreatic infection by Candida albicans occurred in 7% and 22% of patients. Global mortality was 18.5% (10.9% secondary to septic complications), without differences between groups. In patients with persisting systemic complications at day 14 mortality was almost always secondary to septic complications and decreased from 25% (group 1) to 8.8% (group 2) by maintaining antibiotic prophylaxis.

Compared to a 14-day imipenem prophylaxis, a longer antibiotic administration in patients with ANP is not associated with a reduction in the incidence of septic complications of the disease. However, prolonged imipenem administration in patients with persisting systemic complications tends to reduce mortality in ANP compared to a 14-days regimen.

Infectious complications of acute necrotizing pancreatitis (ANP) determine the extent of multiorgan failure and account for 80% of deaths. Prophylactic use of antibiotics can reduce the incidence of these complications. However, the actual indication as well as choice of drug remains a controversial matter. We examined the penetration of moxifloxacin, a new broad-spectrum fluoroquinolone, in healthy and inflamed pancreatic tissue in rats after inducing ANP. The concentration of moxifloxacin in pancreatic tissue and serum was determined 10, 30, 60 and 240 min after the administration of moxifloxacin (5 mg/kg, i.v.). Mean serum concentrations 10 min after administration in rats with ANP were 1,886 ng/ml versus 1,805 ng/ml in healthy controls, and these values decreased to 350 versus 222 ng/ml, respectively, after 240 min. Corresponding concentrations in pancreatic tissue were in the mean 2-3 times higher.

Lung injury is the most pertinent manifestation of extra-abdominal organ dysfunction in pancreatitis. The propensity of this retroperitoneal inflammatory condition to engender a diffuse and life-threatening lung injury is significant. Approximately one third of patients will develop acute lung injury and acute respiratory distress syndrome, which account for 60% of all deaths within the first week. The variability in the clinical course of pancreatitis renders it a vexing entity and makes demonstration of the efficacy of any specific intervention difficult. The distinct pathologic entity of pancreatitis-associated lung injury is reviewed with a focus on etiology and potential therapeutic maneuvers.