Calculated parenteral initial treatment of bacterial infections: Intra-abdominal infections.

This is the seventh chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. The chapter deals with the empirical and targeted antimicrobial therapy of complicated intra-abdominal infections. It includes recommendations for antibacterial and antifungal treatment.

Systematic review and meta-analysis of antibiotic prophylaxis in severe acute pancreatitis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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]). CONCLUSION: In summary, to date there is no evidence that supports the routine use of antibiotic prophylaxis in patients with SAP.

Changing role of surgery in necrotizing pancreatitis: a single-center experience.

BACKGROUND/AIMS: The incidence of acute pancreatitis varies from 5 to 80 per 100,000 inhabitants throughout the world. Recognizing the natural course of severe acute pancreatitis a multidisciplinary approach had become the standard. The strategy of postponing surgical intervention was implemented in the treatment algorithm several years ago. METHODOLOGY: A retrospective analysis of patient data from two five-year periods. The first period was from 01/1992 to 12/1997 (group 1), the second period from 10/2001 to 12/2006 (group 2). RESULTS: In this study, we retrospectively analyzed the impact of this approach on the outcome of our patients with necrotizing pancreatitis. The time interval between onset of disease and first necrosectomy was in the mean 19.5 days in patients of group 1 and 30 days in group 2 (p = 0.015). In group 1, 45/78 patients (57%) were operated on during the first 14 days compared to 8/32 patients (25%; p = 0.002) in group 2. The mortality was 41% in group 1 and 18% in group 2 (p = 0.026). There was also a statistically significant decrease in mortality when first necrosectomy was postponed after day 29 (p = 0.015). CONCLUSION: Our results are in line with several other analyses suggesting that the strategy of postponing surgery in patients with necrotizing pancreatitis is associated with a decreased mortality.

The weak evidence base for antibiotic prophylaxis in severe acute pancreatitis.

BACKGROUND/AIMS: The incidence of acute pancreatitis varies from 5 to 80 per 100,000 inhabitants 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. We therefore analyzed randomized clinical trials, which form the basis of guidelines and recommendations on this topic. RESULTS: One trial demonstrated that antibiotic prophylaxis reduces mortality, but the statistical design of this trial was questionable. Another important trial, showing an effect of antibiotic prophylaxis on the incidence of pancreatic sepsis, used the wrong statistical test to analyze their data. An analysis with the correct test could not confirm this effect. Three randomized clinical trials demonstrated that antibiotic prophylaxis in severe acute pancreatitis could reduce the incidence of extrapancreatic infections. Two trials showed a significant reduction of the overall infection rate; while in one of them peripancreatic and extrapancreatic infections alone were not significantly different. Two double blinded studies could not demonstrate a significant effect of antibiotic prophylaxis on pancreatic/peripancreatic infection, extrapancreatic infection or mortality. CONCLUSION: Our analysis shows that some of the reported significant effects of prophylactic antibiotic treatment are either questionable or less clinically relevant. With regards to reduction in mortality and the incidence of infected pancreatic necrosis, no convincing evidence exists which supports the routine administration of prophylactic antibiotics in severe acute pancreatitis.

Effect of early and late antibiotic treatment in experimental acute pancreatitis in rats.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevention of infectious complications in severe acute pancreatitis with systemic antibiotics: where are we now?

Infectious complications are the leading cause of death in patients with severe acute pancreatitis. Currently, there is controversy concerning the therapeutic possibilities to reduce the incidence of bacterial infection in this disease. Numerous studies are available which apparently support the prophylactic use of antibiotics in patients with necrotizing pancreatitis. The results, however, are contradicting and interpretation is difficult as these studies have used various antibiotic drugs with different application schemes and heterogeneous study end points. This article gives a critical overview of the background of antibiotic treatment in severe acute pancreatitis, the published data on antibiotic treatment and an outlook on the topics that need to be addressed by future research.

Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial.

BACKGROUND & AIMS: Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic. METHODS: A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 x 400 mg/day) + MET (2 x 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped. RESULTS: Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group (P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed. CONCLUSIONS: This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.

Pancreatic fungal infection.

INTRODUCTION: There has been a steady rise in the incidence of pancreatic fungal infections. Even though fungal infections of the pancreas are not very common, they are often nosocomial. AIMS: To review pancreatic fungal infections and to compare their clinical characteristics with those of bacterial pancreatic infections, along with the causes and approaches to diagnosis and treatment. RESULTS: Because of the lack of randomized, prospective trials, standardized recommendations for use of antifungal prophylaxis would be premature. The most important aspect of prophylaxis against pancreatic fungal infection is minimizing the factors that predispose the pancreas to fungal infections. CONCLUSION: Isolation of fungal elements from necrotic pancreatic tissue and treatment of local infection are vital. Treatment of local candidal infection should be initiated with surgical necrosectomy. Systemic antifungal therapy should be started early in the course of the disease, but whether antifungal agents should be added to the prophylactic antibiotic regimens for patients with necrotizing pancreatitis remains questionable.

Gastrointestinal disorders of the critically ill. Shock and acute pancreatitis.

Shock and pancreatitis are closely associated. Shock can be a sequel of severe pancreatitis and systemic shock may induce pancreatitis. This chapter discusses both features with regard to their clinical and pathophysiological characteristics.

Characteristics of infection with Candida species in patients with necrotizing pancreatitis.

This study focuses on the relevance of Candida infection (albicans and non-albicans) in patients with necrotizing pancreatitis. Altogether, 92 patients with infected pancreatic necrosis were reviewed for Candida infection. All patients underwent surgical necrosectomy for infected pancreatic necrosis. Data from patients with Candida growth in intraoperative smears were compared to those obtained from patients without Candida infection. There were 22 patients (24%) with Candida infection. Patients with or without Candida infection were comparable regarding age, gender, etiology, and severity scores at admission. Candida patients suffered a higher mortality (64% vs.19%, p = 0.0001) and experienced more systemic complications (3.2 +/- 1.6 vs. 2.1 +/- 1.4; p= 0.004) than patients without Candida. Preoperative antibiotics were given significantly longer prior to Candida infection (19.0 +/- 13.2 vs. 6.4 +/- 10.3 days; p < 0.0001). With regard to the concomitant spectrum of bacteria, solitary gram-negative infection was rare in Candida patients (5% vs. 43%, p =0.0006). The presence of Candida in patients with infected pancreatic necrosis is associated with increased mortality. Our data provide evidence that application of antibiotics contributes to the development of Candida infection and to changes in the bacterial spectrum of infected necrosis with an increase in the incidence of gram-positive infection.