The microbiology of infected pancreatic necrosis

Background

Acute pancreatitis (AP) continues to cause significant morbidity and mortality, especially when it leads to infected pancreatic necrosis (IPN). Modern treatment of IPN frequently involves prolonged courses of antibiotics in combination with minimally invasive therapies. This study aimed to update the existing evidence base by identifying the pathogens causing IPN and therefore aid future selection of empirical antibiotics.

Value of routine clinical tests in predicting the development of infected pancreatic necrosis in severe acute pancreatitis

Objective. 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. Material and methods. 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). Results. 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 13×10⁹/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. Conclusions. 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.     

Step-up mini-invasive surgery for infected pancreatic necrosis: Results from prospective cohort study

ObjectivesTo investigate the clinical efficacy and success predictors of mini-invasive techniques in the treatment of infected pancreatic necrosis (IPN).MethodsIPN patients admitted to our clinic for treatment by mini-invasive techniques were included in this study prospectively. Treatment was divided into four sequential phases: percutaneous catheter drainage (PCD), mini-incision drainage (MID), video assisted debridement (VAD) and open surgery. Patients progressed to next phase if the infection cannot be controlled. The frequency of surgery, treatment duration, cure rate, incidence of complication and overall mortality were recorded. Risk factors for failure of PCD and MID procedures were detected by logistic regression including demographics, disease severity and morphologic characteristics.ResultsFrom January 2012 to March 2015, a total of 54 consecutive IPN patients were treated, with an average age of 51.2 ± 3.1 years. Of the 54 cases, 18 (33.3%) were cured after PCD; 13 (24.1%) with uncontrolled infection were cured after MID; and the remaining 19 cases (35.2%) were cured after VAD. No open surgery was performed. Overall mortality was 7.4% (4/54), and the incidence of complications was 12.9% (7/54). In multivariable regression, the following factors were associated with high failure rate for both PCD and MID: heterogeneous fluid collection (odds ratio (OR) = 3.14; 95% confidence interval (CI): 1.32 ～ 4.25, P = 0.001 for PCD; OR = 2.99; 95% CI: 1.52 ～ 5.10, P = 0.006 for MID), multiple infected collections (OR = 4.51; 95% CI: 2.94 ～ 8.63; P = 0.000 for PCD; OR = 4.17; 95% CI: 2.77 ～ 8.12, P = 0.000 for MID), CT severity index (0 ～ 3/4 ～ 6/7 ～ 10: OR = 2.16; 95% CI: 1.83 ～ 3.62, P = 0.031 for PCD; OR = 2.72; 95% CI: 1.78 ～ 4.10, P = 0.005 for MID).ConclusionsStep-up mini-invasive techniques can be considered a first choice in the treatment of IPN. CT is effective to predict success of PCD and MID.     

Walled-off pancreatic necrosis

Walled-off pancreatic necrosis (WOPN), formerly known as pancreatic abscess is a late complication of acute pancreatitis. It can be lethal, even though it is rare. This critical review provides an overview of the continually expanding knowledge about WOPN, by review of current data from references identified in Medline and PubMed, to September 2009, using key words, such as WOPN, infected pseudocyst, severe pancreatitis, pancreatic abscess, acute necrotizing pancreatitis (ANP), pancreas, inflammation and al...     

Modified single transluminal gateway transcystic multiple drainage technique for a huge infected walled-off pancreatic necrosis: A case report

We report a successful endoscopic ultrasonographyguided drainage of a huge infected multilocular walledoff necrosis(WON) that was treated by a modified single transluminal gateway transcystic multiple drainage(SGTMD) technique. After placing a widecaliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward-viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases.     

Prognostic factors of critical acute pancreatitis: A prospective cohort study

BackgroundPatients with critical acute pancreatitis (CAP) have the highest risk of mortality. However, there have been no studies specifically designed to evaluate the prognostic factors of CAP.Aims & methodsThis was a prospective observational cohort study involving patients with CAP. Three aspects including organ failure, (peri)pancreatic necrotic fluid cultures and surgical interventions were analyzed specifically to identify prognostic factors.ResultsOf the 102 consecutive patients with CAP, 83 patients (81.4%) received step-up surgical treatment, the mortality of the step-up group was 25.3% (21/83). 19 patients (18.6%) underwent step-down surgical treatment, the mortality of the step-down group was 57.9% (11/19). Overall mortality in the whole cohort was 31.4% (32/102). Multivariate analysis of death predictors indicated that multiple organ failure (MOF) (OR = 5.3; 95% CI, 1.5–18.2; p = 0.008), long duration (≥5 days) of organ failure (OR = 6.4; 95% CI, 1.2–54.3; p = 0.029), multidrug-resistant organisms (MDROs) infection (OR = 4.6; 95% CI, 1.3–15.8; p = 0.013), OPN (OR = 3.7; 95% CI, 1.5–8.8; p = 0.004) and step-down surgical treatment (OR = 3.5; 95% CI, 1.2–10.1; p = 0.019) were significant factors.ConclusionAmong patients with CAP, MOF, long duration (≥5 days) of organ failure, MDROs infection, OPN and step-down surgical treatment were identified as the predictors of mortality.     

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis

BackgroundMortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined.ObjectivesTo determine the association between mortality and the development of early IPN.MethodsInternational multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses.ResultsA total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63–3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70–13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05).ConclusionEarly infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.     

Dissecting the effect of moxifloxacin in mice with infected necrosis in taurocholate induced necrotizing pancreatitis

ObjectivesTo investigate the limited benefit of antibiotics in ameliorating the outcome of acute necrotizing pancreatitis, we analyzed antibiotic therapy in primarily infected necrotizing pancreatitis in mice with respect to the local pancreatic pathology as well as systemic, pancreatitis induced adverse events.MethodsSterile pancreatic necrosis (SN) was induced by retrograde injection of 4% taurocholate in the common bile duct of Balb/c mice. Primarily infected pancreatic necrosis (IN) was induced by co-injecting 10⁸ CFU/ml Escherichia coli. 10 mg/kg of moxifloxacin was administered prior to pancreatitis induction (AN). After 24 h, animals were sacrificed to examine serum as well as organs for signs of SIRS.ResultsMoxifloxacin significantly reduced bacterial count in pancreatic lysates of animals with infected pancreatic necrosis (IN 4.1·10⁷ ± 2.4·10⁷ vs. AN 4.9·10⁴ ± 2.6·10⁴ CFU/g; p < 0.001). However, it did not alter pancreatic histology or pulmonary damage (Histology score: IN 23.8 ± 2.7 vs. AN 22.6 ± 1.7). Moxifloxacin reduced systemic immunoactivation (Serum IL-6: IN 330.5 ± 336.6 vs. 38.7 ± 25.5 pg/ml; p < 0.001), hypoglycemia (serum glucose: IN 105.8 ± 12.7 vs. AN 155.7 ± 39.5 mg/dl; p < 0.001), and serum aspartate aminotransferase (IN 606 ± 89.7 vs. AN 255 ± 52.1; p < 0.05). These parameters were significantly increased in animals with necrotizing pancreatitis.ConclusionIn the experimental setting, initial antibiotic therapy with moxifloxacin in acute infected necrotizing pancreatitis in mice does not have a beneficial impact on pancreatic pathology or pulmonary damage. However, other systemic complications induced by infected necrosis in acute pancreatitis are reduced by the administration of moxifloxacin.     

Infected pancreatic necrosis: not necessarily a late event in acute pancreatitis

It is widely believed that infection of pancreatic necrosis is a late event in the natural course of acute pancreatitis. This paper discusses the available data on the timing of pancreatic infection. It appears that infected pancreatic necrosis occurs early in almost a quarter of patients. This has practical implications for the type, timing and duration of preventive strategies used in these patients. There are also implications for the classification of severity in patients with acute pancreatitis. Given that the main determinants of severity are both local and systemic complications and that they can occur both early and late in the course of acute pancreatitis, the classification of severity should be based on their presence or absence rather than on when they occur. To do otherwise, and in particular overlook early infected pancreatic necrosis, may lead to a misclassification error and fallacies of clinical studies in patients with acute pancreatitis.     

Application of metagenomic next-generation sequencing for suspected infected pancreatic necrosis

BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly used for the clinical diagnosis of infectious diseases, but there is a paucity of data regarding the application of mNGS in the early diagnosis of infected pancreatic necrosis (IPN).ObjectiveTo investigate the clinical application value of mNGS in the pathogenic diagnosis of IPN.MethodsForty-two patients with suspected IPN were prospectively and consecutively enrolled from August 2019 to August 2021. Blood samples were collected for mNGS and microbial culture simultaneously during fever (T ≥ 38.5 °C). For patients who had indications of surgical interventions, peri-pancreatic specimens were collected for mNGS and microbial culture simultaneously during the first surgical intervention to confirm IPN. The clinical performance of mNGS and microbial culture were compared.ResultsA total of 21 patients (50.0%) were confirmed to have IPN during hospitalization. The sensitivity of blood mNGS was significantly higher than blood culture (95.2% vs. 23.8%, P < 0.001) in diagnosing IPN. The negative predictive value of blood mNGS was 90.0%. The turnaround time of mNGS was significantly shorter than that of microbial culture [(37.70 ± 1.44) vs. (115.23 ± 8.79) h, P < 0.01] and the average costs of mNGS accounted for 1.7% of the average total cost of hospitalization. The survival analysis demonstrates that the positive blood mNGS result was not associated with increased mortality (P = 0.119).ConclusionsWith more valuable diagnostic performance and shorter turnaround time, clinical mNGS represents a potential step forward in the early diagnosis of IPN.     

Site and size of extrapancreatic necrosis are associated with clinical outcomes in patients with acute necrotizing pancreatitis

BackgroundThe site and size of extrapancreatic necrosis (EPN) as assessed on computed tomography may influence the severity of acute necrotizing pancreatitis (ANP). The objective of the study was to evaluate the impact of site and size of EPN on the clinical outcomes in patients with acute necrotizing pancreatitis (ANP).Method and materialsThis retrospective study comprised of consecutive patients with ANP who were admitted between January 2017 and March 2019. Patients in whom the initial contrast enhanced CT showed EPN were eligible for inclusion. The site, volume and maximum dimension of EPN were recorded. The severity of AP and modified CT severity index (MCTSI) was calculated. Clinical outcomes were recorded.ResultsA total of 119 patients (mean age, 37.56 years, 91 males) were included. There was a significant association between the location of EPN and the outcome parameters. The left posterior pararenal collections were significantly associated with mortality (P = 0.041), left paracolic gutter collections with the length of hospitalisation (LOH) (P = 0.014), and right paracolic gutter and mesenteric collections with the intensive care unit (ICU) stay (P = 0.024, and P = 0.021, respectively). There was a significant correlation between the volume and the maximum dimension of collection with LOH and ICU stay. The area under the receiver operating characteristic curve for volume, maximum dimension and MCTSI for predicting death was 0.724 (95% CI, 0.612–0.837), 0.644 (95% CI, 0.516–0.772) and 0.574 (95% CI, 0.452–0.696), respectively.ConclusionThe site and size of EPN provide reliable and objective information for assessing clinical outcomes in patients with ANP.     

Walled-off pancreatic necrosis: Wishing our pancreatitis nomenclature was correct

The ultimate reason why pancreatologists have strived to establish definitions for inflammatory pathologies of the pancreas is to improve patient care.Although the Atlanta Classification has been used for around for 17 years,considerable misunderstanding of the key elements of the nomenclature still persists.While a recent article by Stamatakos et al aimed to deal with an entity not clearly def ined in the 1993 document,it is replete with factual and conceptual errors as well as contradictory statements.     

Outcomes of infected pancreatic necrosis complicated with duodenal fistula in the era of minimally invasive techniques

Abstract

Background: Duodenal fistula (DF) was reportedly thought to be the second most common type of gastrointestinal fistula secondary to acute necrotizing pancreatitis. However, infected pancreatic necrosis (IPN) associated DF (IPN-DF) was rarely specifically reported in the literature. The outcome of IPN-DF was also less well recognized, especially in the era of minimally invasive techniques. A retrospective cohort study was designed mainly focused on the management and outcomes of IPN-DF in the era of minimally invasive techniques.

Methods: One hundred and twenty-one consecutive patients diagnosed with IPN between January 2015 and May 2018 were enrolled retrospectively. Among them, 10 patients developed DF. The step-up minimal invasive techniques were highlighted and outcomes were analyzed.

Results: Compared with patients without IPN-DF, patients with IPN-DF had longer hospital stay (95.8 vs. 63.5 days, p?p?>?.05). The median interval between the onset of acute pancreatitis (AP) and detection of DF was 2.4 months (1–4 months). The median duration of DF was 1.5 months (0.5–3 months). Out of the 10 patients with DF, 9 had their fistulas resolve spontaneously over time by means of controlling the source of infection with the use of minimally invasive techniques and providing enteral nutritional support, while one patient died of uncontrolled sepsis. No open surgery was performed. On follow-up, the 9 patients recovered completely and remained free of infection and leakage.

Conclusion: IPN-DF could be managed successfully using minimally invasive techniques in specialized acute pancreatitis (AP) center. Patients with IPN-DF suffered from a longer hospital stay, but similar mortality rate compared with patients without DF.     

Analysis of the delayed approach to the management of infected pancreatic necrosis

AIM: To analyze outcomes of delayed single-stage necrosectomy after early conservative management of patients with infected pancreatic necrosis (IPN) associated with severe acute pancreatitis (SAP). METHODS: Between January 1998 and December 2009, data from patients with SAP who developed IPN and were managed by pancreatic necrosectomy were analyzed. RESULTS: Fifty-nine of 61 pancreatic necrosectomies were performed by open surgery and 2 laparoscopically. In 55 patients, single-stage necrosectomy could be p...     

Spectrum of microorganisms in infected walled-off pancreatic necrosis – Impact on organ failure and mortality

ObjectiveData on the microbial spectrum in infected pancreatic necrosis are scarce. Only few studies have addressed this issue in a larger, consecutive group of patients treated by a standardized algorithm. Since 2005 endoscopic, transmural drainage and necrosectomy (ETDN) has been the treatment of choice for walled-off necrosis in our centre. The present study evaluated the microbial spectrum of infected pancreatic necrosis and the possible relationship between infected necrosis, organ failure, and mortality. Furthermore, we investigated whether the aetiology of pancreatitis, use of external drainage, and antibiotic treatment influenced the microbial findings.MethodsRetrospective review of medical charts on 78 patients who underwent ETDN in our tertiary referral centre between November 2005 and November 2011.ResultsTwenty-four patients (31%) developed one or more organ failures, 23 (29%) needed treatment in the intensive care unit (ICU), and 9 (11%) died during hospital admission. The prevailing microbial findings at the index endoscopy were enterococci (45%), enterobacteriaceae (42%), and fungi (22%). There was a significant association between the development of organ failure (p < 0.001), need of treatment in ICU (p < 0.002), in-hospital mortality (p = 0.039) and infected necrosis at the time of index endoscopy. Enterococci (p < 0.0001) and fungi (p = 0.01) were found more frequently in patients who died during admission as compared to survivors.ConclusionDifferent microbes in pancreatic necrosis may influence the prognosis. We believe that a detailed knowledge on the microbial spectrum in necrotizing pancreatitis may be utilized in the treatment to improve the outcome.     

Efficacy of antibiotic penetration into pancreatic necrosis

Background: Infection of pancreatic necrosis is the most dangerous complication of acute necrotizing pancreatitis. Infection is undoubtedly caused by the endogenous flora of the host. This is why prophylaxis with a broad-spectrum antibiotic is considered an effective procedure. However, two aspects should be taken into consideration when choosing the antibiotic; it should have the spectrum of action consistent with the pathogens and it should penetrate effectively to the necrotic tissue of the pancreas. The aim of the study was to estimate the efficacy of piperacillin/tazobactam penetration into pancreatic necrosis in patients who received intravenous infusion of piperacillin/tazobactam at a dose of 4.5 g every 8 h for 14–21 days, as the prophylaxis in the treatment of acute necrotizing pancreatitis. Patients and methods: Necrotic tissue of the pancreas and the inflammatory ascites surrounding the pancreas were derived from 15 patients (male, 10; female, 5; mean age 46 years), who underwent laparatomy due to pancreatic necrosis after treatment for 14–21 days. Tissue/fluid samples were investigated for the concentration of the antibiotic by fluoroscopic/spectroscopic methods of registration in an HPLC system. Results: The mean concentration of piperacillin/tazobactam was established as 120 mg/kg (SD±34) in the necrotic pancreatic tissue and as 183 mg/kg (SD±37) in the inflammatory pancreatic ascites. Conclusions: In patients with acute necrotizing pancreatitis, the study indicates effective penetration of piperacillin/tazobactam to the necrotic pancreatic tissue and to the inflammatory ascites surrounding the pancreas.     

Isolated peripancreatic necrosis (PPN) is associated with better clinical outcomes compared with combined pancreatic and peripancreatic involvement (CPN)- a systematic review and meta-analysis

Background and aimsPeripancreatic necrosis (PPN) is considered as a distinct entity with a better outcome when compared with combined pancreatic and peripancreatic necrosis (CPN), but there is no systematic review to summarize the evidence. Our study aimed to perform a meta-analysis of existing observational studies comparing the outcomes of PPN with CPN.MethodsStudies in adult patients comparing the outcomes of PPN and CPN from PubMed, Medline, and Scopus databases from inception to November 2018 were systematically searched. The primary outcome was mortality, and secondary outcomes included multi-organ failure, persistent organ failure, infected necrosis, need for interventions including open necrosectomy. Pooled adjusted odds ratios, and 95% confidence intervals (CI) were obtained by the random-effects model. Forrest plots were constructed to show the summary pooled estimate. Heterogeneity was assessed by using I2 measure of inconsistency.ResultsA total of 6 studies involving 1851 patients (1295 (70%) with CPN and 556 (30%) with PPN) were included. Patients with CPN had a significantly higher mortality (OR 2.49, 95% CI: 1.61–3.87), risk for multi-organ failure (OR 3.24, 95% CI: 2.38–4.43), persistent organ failure (OR 2.79, 95% CI: 1.53–5.08), and infected necrosis (OR 6.21, 95% CI: 3.85–10.03). They underwent more interventions (OR 5.86, 95% CI: 3.69–9.32), including open necrosectomy (OR 5.04, 95% CI: 3.33–7.63). Heterogeneity was low (I2 = 18.1, p = 0.296), and there was no publication bias.ConclusionIsolated peripancreatic necrosis portends an overall better prognosis when compared to necrosis involves pancreatic parenchyma. Clinicians should recognize this distinction for management decisions.