Bacterial Translocation In Patients Research Articles

Proton pump inhibitor treatment aggravates bacterial translocation in patients with advanced cirrhosis and portal hypertension.

Long-term prescription of proton pump inhibitors (PPIs) in patients with cirrhosis is common practice. However, in recent years, several observational studies have reported increased complications and negative prognostic effects of PPI treatment in these patients. Judging the significance of these associations is complicated by the fact that a plausible underlying pathomechanism has not been identified so far. In the present study, we address this important issue by investigating the impact of PPI treatment on subclinical bacterial translocation from the gut into the blood stream in patients with advanced cirrhosis and portal hypertension. Indeed, we report significantly aggravated bacterial translocation in cirrhosis patients receiving PPI treatment. This finding is highly relevant, as bacterial translocation is known to promote the development of complications and impair prognosis in patients with cirrhosis. Hence, the present study could establish a plausible link between PPI treatment and adverse effects in cirrhosis.

Recombinant VEGF-C (Cys156Ser) improves mesenteric lymphatic drainage and gut immune surveillance in experimental cirrhosis

Lymphatic vessels (LVs) are crucial for maintaining abdominal fluid homoeostasis and immunity. In cirrhosis, mesenteric LVs (mLVs) are dilated and dysfunctional. Given the established role of vascular endothelial growth factor-C (VEGF-C) in improving LVs, we hypothesised that VEGF-C treatment could ameliorate the functions of mLVs in cirrhosis. In this study, we developed a nanoformulation comprising LV-specific growth factor, recombinant human VEGF-C (Cys156Ser) protein (E-VEGF-C) and delivered it orally in different models of rat cirrhosis to target mLVs. Cirrhotic rats were given nanoformulation without VEGF-C served as vehicles. Drainage of mLVs was analysed using tracer dye. Portal and systemic physiological assessments and computed tomography were performed to measure portal pressures and ascites. Gene expression and permeability of primary mesenteric lymphatic endothelial cells (LyECs) was studied. Immune cells in mesenteric lymph nodes (MLNs) were quantified by flow cytometry. Endogenous and exogenous gut bacterial translocation to MLNs was examined. In cirrhotic rats, mLVs were dilated and leaky with impaired drainage. Treatment with E-VEGF-C induced proliferation of mLVs, reduced their diameter, and improved functional drainage. Ascites and portal pressures were significantly reduced in E-VEGF-C rats compared with vehicle rats. In MLNs of E-VEGF-C animals, CD8+CD134+ T cells were increased, whereas CD25+ regulatory T cells were decreased. Both endogenous and exogenous bacterial translocation were limited to MLNs in E-VEGF-C rats with reduced levels of endotoxins in ascites and blood in comparison with those in vehicle rats. E-VEGF-C treatment upregulated the expression of vascular endothelial-cadherin in LyECs and functionally improved the permeability of these cells. E-VEGF-C treatment ameliorates mesenteric lymph drainage and portal pressure and strengthens cytotoxic T-cell immunity in MLNs in experimental cirrhosis. It may thus serve as a promising therapy to manage ascites and reduce pathogenic gut bacterial translocation in cirrhosis. A human recombinant pro-lymphangiogenic growth factor, VEGF-C, was encapsulated in nanolipocarriers (E-VEGF-C) and orally delivered in different models of rat liver cirrhosis to facilitate its gut lymphatic vessel uptake. E-VEGF-C administration significantly increased mesenteric lymphatic vesselproliferation and improved lymph drainage, attenuating abdominal ascites and portal pressures in the animal models. E-VEGF-C treatment limited bacterial translocation to MLNs only with reduced gut bacterial load and ascitic endotoxins. E-VEGF-C therapy thus holds the potential to manage ascites and portal pressure and reduce gut bacterial translocation in patients with cirrhosis.

Functionalized gold nanomaterials in the detection of bacterial translocation in patients with acute intestinal obstruction

Functionalized gold nanomaterials in the detection of bacterial translocation in patients with acute intestinal obstruction

Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options.

Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.

Enhanced Bacteremia in Dextran Sulfate-Induced Colitis in Splenectomy Mice Correlates with Gut Dysbiosis and LPS Tolerance.

Because both endotoxemia and gut dysbiosis post-splenectomy might be associated with systemic infection, the susceptibility against infection was tested by dextran sulfate solution (DSS)-induced colitis and lipopolysaccharide (LPS) injection models in splenectomy mice with macrophage experiments. Here, splenectomy induced a gut barrier defect (FITC-dextran assay, endotoxemia, bacteria in mesenteric lymph nodes, and the loss of enterocyte tight junction) and gut dysbiosis (increased Proteobacteria by fecal microbiome analysis) without systemic inflammation (serum IL-6). In parallel, DSS induced more severe mucositis in splenectomy mice than sham-DSS mice, as indicated by mortality, stool consistency, gut barrier defect, serum cytokines, and blood bacterial burdens. The presence of green fluorescent-producing (GFP) E. coli in the spleen of sham-DSS mice after an oral gavage supported a crucial role of the spleen in the control of bacteria from gut translocation. Additionally, LPS administration in splenectomy mice induced lower serum cytokines (TNF-α and IL-6) than LPS-administered sham mice, perhaps due to LPS tolerance from pre-existing post-splenectomy endotoxemia. In macrophages, LPS tolerance (sequential LPS stimulation) demonstrated lower cell activities than the single LPS stimulation, as indicated by the reduction in supernatant cytokines, pro-inflammatory genes (iNOS and IL-1β), cell energy status (extracellular flux analysis), and enzymes of the glycolysis pathway (proteomic analysis). In conclusion, a gut barrier defect after splenectomy was vulnerable to enterocyte injury (such as DSS), which caused severe bacteremia due to defects in microbial control (asplenia) and endotoxemia-induced LPS tolerance. Hence, gut dysbiosis and gut bacterial translocation in patients with a splenectomy might be associated with systemic infection, and gut-barrier monitoring or intestinal tight-junction strengthening may be useful.

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder.

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation.Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3+ Tregs and their distribution on the naïve (TN), effector (TE), central (TCM), and effector memory(TEM) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay.Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the TN, TE, TCM, and TEM stages. The percentage of Tregs cells at TN stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients.Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25highFoxP3+ and CD25lowFoxP3+ subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.

Microbiome alterations are related to an imbalance of immune response and bacterial translocation in BDL-rats.

Objective(s):Bacterial translocation in patients with cirrhosis is an important triggering factor for infections and mortality. In the bile duct ligation (BDL) model, crucial players of bacterial translocation are still unknown. This study aims to determine the interrelation between microbiome composition in the colon, mesenteric lymph nodes, and liver, as well as the local inflammatory microenvironment in the BDL model.Materials and Methods:Liver damage was assayed by Masson trichrome staining, and hepatic enzymes. The diversity of microbiota in colon stools, mesenteric lymph nodes, and liver was determined by 16S rRNA pyrosequencing. Cytokine expression in mesenteric lymph nodes was analyzed by qRT-PCR.Results:Our results show that Proteobacteria was the predominant phylum found to translocate to mesenteric lymph nodes and liver in cirrhotic rats. Bile duct ligation induces a drastic intestinal dysbiosis, revealed by an increased relative abundance of Sarcina, Clostridium, Helicobacter, Turicibacter, and Streptococcus genera. However, beneficial bacteria, such as Lactobacillus, Prevotella and Ruminococcus were found to be notably decreased in BDL groups. Mesenteric pro-inflammatory (TNF-α, IL-1β, IL-6, TLR-4) and regulatory (TGF-β, Foxp3, and IL-10) molecules at 30 days post-BDL were significantly increased. Conversely, TGF-β and Foxp3 were significantly augmented at 8 days post-BDL. Conclusion:Dysbiosis in the colon and mesenteric lymph nodes is linked to an imbalance in the immune response; therefore, this may be an important trigger for bacterial translocation in the BDL model.

Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention.

Increased bacterial translocation (BT) across the gut barrier due to greater intestinal permeability (IP) is seen across a range of conditions, including alcohol-related liver disease (ArLD). The phenomenon of BT may contribute to both the pathogenesis and the development of complications in ArLD. There are a number of methods available to assess IP and in this review we look at their various advantages and limitations. The knowledge around BT and IP in ArLD is also reviewed, as well as the therapeutic strategies currently in use and in development.

Safety of two different doses of simvastatin plus rifaximin in decompensated cirrhosis (LIVERHOPE-SAFETY): a randomised, double-blind, placebo-controlled, phase 2 trial

Statins have beneficial effects on intrahepatic circulation and decrease portal hypertension and rifaximin modulates the gut microbiome and might prevent bacterial translocation in patients with cirrhosis. Therefore, this drug combination might be of therapeutic benefit in patients with decompensated cirrhosis. However, there is concern regarding the safety of statins in patients with decompensated cirrhosis. We assessed the safety of two different doses of simvastatin, in combination with rifaximin, in patients with decompensated cirrhosis. We did a double-blind, randomised, placebo-controlled, phase 2 trial in patients with decompensated cirrhosis and moderate-to-severe liver failure from nine university hospitals in six European countries (Italy, France, Holland, Germany, the UK, and Spain). Patients older than 18 years with Child-Pugh class B or C disease were eligible. We randomly assigned patients (1:1:1) to receive either simvastatin 40 mg/day plus rifaximin 1200 mg/day, simvastatin 20 mg/day plus rifaximin 1200 mg/day, or placebo of both medications for 12 weeks. Randomisation was stratified according to Child-Pugh class (B vs C) and restricted using blocks of multiples of three. The primary endpoint was development of liver or muscle toxicity, as defined by changes in liver aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), alkaline phosphastase, and creatine kinase. The study is registered with the European Union Clinical Trials Register, 2016-004499-23, and with ClinicalTrials.gov, NCT03150459. The study recruitment period was between July 28, 2017, and Jan 2, 2018. Follow-up finished on March 12, 2018. 50 patients were randomly assigned to simvastatin 40 mg/day plus rifaximin 1200 mg/day (n=18), simvastatin 20 mg/day plus rifaximin 1200 mg/day (n=16), or placebo of both medications (n=16). Six patients (two from each group) were excluded. Therefore, the full analysis set included 44 patients (16 in the simvastatin 40 mg/day plus rifaximin 1200 mg/day group, 14 in the simvastatin 20 mg/day plus rifaximin mg/day group, and 14 in the placebo group). After a safety analyses when the first ten patients completed treatment, treatment was stopped prematurely in the simvastatin 40 mg/day plus rifaximin group due to recommendations by the data safety monitoring board. Patients in the simvastatin 40 mg/day plus rifaximin group showed a significant increase in AST and ALT compared with the placebo group (mean differences between the groups at the end of treatment for AST 130 IU/L [95% CI 54 to 205; p=0·0009] and for ALT 61 IU/L [22 to 100; p=0·0025]. We observed no significant differences at 12 weeks in AST and ALT between the simvastatin 20 mg/day plus rifaximin and placebo group (for AST -14 IU/L [-91 to 64; p=0·728] and for ALT -8 IU/L [-49 to 33; p=0·698]). We observed no significant differences in alkaline phosphatase between the the simvastatin 40 mg/day plus rifaximin or the simvastatin 20 mg/day plus rifaximin groups compared with placebo. Patients in the simvastatin 40 mg/day plus rifaximin group showed an increase in creatine kinase at the end of treatment compared with patients in the placebo group (1009 IU/L [208 to 1809]; p=0·014). We observed no significant changes in creatine kinase in the simvastatin 20 mg/day plus rifaximin group (4·2 IU/L [-804 to 813]; p=0·992). Three (19%) patients in the simvastatin 40 mg/day group developed liver and muscle toxicity consistent with rhabdomyolysis. The number of patients who stopped treatment because of adverse events was significantly higher in the simvastatin 40 mg/day plus rifaximin group (nine [56%] of 16 patients) compared with the other two groups (two [14%] of 14 for both groups; p=0·017). There were no serious unexpected adverse reactions reported during the study. Treatment with simvastatin 40 mg/day plus rifaximin in patients with decompensated cirrhosis was associated with a significant increase in adverse events requiring treatment withdrawal, particularly rhabdomyolysis, compared with simvastatin 20 mg/day plus rifaximin. We recommend simvastatin 20 mg/day as the dose to be used in studies investigating the role of statins in patients with decompensated cirrhosis. Horizon 20/20 European programme.

Association between intestinal barrier and bacterial translocation in patients with liver cirrhosis

Decompensated liver cirrhosis has various life-threatening complications such as spontaneous bacterial peritonitis, hepatic encephalopathy, and sepsis, and the development of such complications is closely associated with bacterial translocation. Pathological bacterial translocation in patients with liver cirrhosis is caused by the impairment of intestinal barrier function, and thus bacteria can cross the intestinal barrier and enter the mesenteric lymph nodes or other sites. Therefore, a better understanding of the association between intestinal barrier and bacterial translocation in liver cirrhosis can provide new theoretical support for the treatment of liver cirrhosis. This article discusses the four major components of the intestinal barrier, namely the mechanical barrier, the immune barrier, the chemical barrier, and the biological barrier, as well as their changes during bacterial translocation.

Mucosal Barrier Injury Laboratory Confirmed Bloodstream Infections

To increase the awareness of the new CDC survey definition of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection (MBI-LCBI). We included a comparison of the definition of Central Line-Associated Bloodstream Infection (CLABSI), with a high sensitivity but low specificity and Catheter-Related Bloodstream Infection (CRBSI). There are other parameters like the difference between the size of the inoculum (catheter lumen vs peripheral), that increased specificity and is useful for research and clinical decisions. Also, MBI-LCBI secondary to bacterial translocation in patients who had received myeloablative chemotherapy with severe neutropenia is not related to central venous catheter care. This new survey definition is useful for better classification of nosocomial bloodstream infections among patients receiving myeloablative chemotherapy and has impacted diminishing the incidence of CLABSI, which has probably has been overestimated in patients with hematological malignancies. The concept of MBI-LCBI should not be limited to survey purposes; it is also useful for clinical decisions. We propose to incorporate a second set of blood cultures obtained 48 hours after antibiotic treatment onset, one through the line of the CVC and another one at a peripheral site; if negative, it avoids unnecessary removal of the catheter in patients with severe neutropenia or, on the contrary, if positive blood cultures persist after 48 hours of antimicrobial therapy, there is a clear indication for central venous catheter removal. The definition of MBI-LCBI avoids over-diagnosis of CLABSI in patients receiving myeloablative chemotherapy with severe neutropenia.

The Influence of Carbon Dioxide Pneumoperitoneum on Systemic Inflammatory Response Syndrome and Bacterial Translocation in Patients With Bacterial Peritonitis Caused by Acute Appendicitis.

To explore the influence of carbon dioxide pneumoperitoneum (CDP) on system inflammatory response syndrome (SIRS) and bacterial translocation (BT) in patients with bacterial peritonitis (BP) caused by acute appendicitis (AA). Eighty-six consecutive subjects were randomly divided into the laparoscopy and laparotomy groups (n = 44 and n = 42, respectively). The levels of white blood cells (WBC), C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) of the 2 groups were tested preoperatively and at days 1, 2, and 4 after surgery. Blood and secretion culture was performed to verify whether septicemia or incision infection occurred, respectively. And the abdominal ultrasound or computed tomography scanning was used to diagnose peritoneal abscess for the suspected patients. The essential risk factors related to the aggravation of SIRS were analyzed through analysis of variance and binary logistic regression. The postoperative blood levels of WBC, CRP, TNF-α, and IL-6 on day 4 in the laparoscopy group were significantly lower than those in the control group (all Ps < .05). The differences in incidence rates of septicemia and peritoneal abscess between the CDP and control groups were not statistically significant ( P > .05). Nevertheless, the incision infection rate in the laparoscopy group was apparently lower than that in the control group (4.55% vs 19.04%, P = .047). Analysis of variance and binary logistic regression showed that the non-pneumoperitoneum, pathological type of appendicitis, and multidrug resistant infections were the 3 major risk factors for SIRS (the P values were .001, .019, and .012, respectively). It was found that CDP is safe for BP and could be a potential protective factor to mitigate BP effectively, indicating that the performance of laparoscopy operation under CDP is feasible to control SIRS; at the same time, CDP would not raise the incidence rate of BT.

Does bacterial translocation influence the postoperative infections in splenectomized patients after abdominal trauma?

BackgroundSome studies suggested that after abdominal trauma, postoperative infections are associated with bacterial translocation, whereas others have not replicated these findings. We have assessed the bacterial translocation and postoperative infections in patients undergoing splenectomy after abdominal trauma, using a very homogeneous study population. MethodsWe consecutively studied, in a prospective observational clinical study, 125 patients who required urgent surgical treatment (splenectomy) following blunt abdominal trauma. For bacterial translocation identification, tissue samples were taken from liver, spleen and mesenteric lymph nodes (MLNs). Postoperative infectious complications in these patients were registered, confirmed by a positive culture obtained from the septic focus. Associations between clinical variables, bacterial translocation presence, and postoperative infection development were established. ResultsBacterial translocation was detected in 47 (37.6%) patients. Postoperative infections were present in 29 (23.2%) patients. A significant statistical difference was found between postoperative infections in patients with bacterial translocation evidence (22 of 47 patients: 46.8%) in comparison with patients without bacterial translocation (7 of 78 patients: 8.9%) (P < 0.05). After multivariate adjustment analysis: a) the bleeding ≥ 1500 mL was significantly associated with the risk of bacterial translocation and, b) bacterial translocation was significantly associated with the risk of postoperative infections. Bacterial strains isolated from infection sites were the same as those cultured in MLNs in 48.3% of the cases (n = 14 of 29). ConclusionsThere is higher risk of bacterial translocation in patients who required urgent surgical treatment (splenectomy) following blunt abdominal trauma and it is associated with a significant higher number of postoperative infections.

Arpin contributes to bacterial translocation and development of severe acute pancreatitis.

To assess the impact of Arpin protein and tight junction (TJ) proteins in the intestinal mucosa on bacterial translocation in patients with severe acute pancreatitis (SAP). Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation (BT) in the blood [i.e., BT(+) and BT(-)]. Twenty healthy individuals were included in the control group. BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting. Bacterial DNA was detected in the peripheral blood of 62.0% of patients (31/50) with SAP. The expression of TJ proteins in SAP patients was lower than that in healthy controls. In contrast, Arpin protein expression in SAP patients was higher than in healthy controls (0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05). Among SAP patients, those positive for BT showed a higher level of claudin-2 expression (0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin (OC) (0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1 (0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT (-) patients. Moreover, the level of Arpin expression in BT (+) patients was higher than in BT (-) patients (0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05). Arpin protein affects the expression of tight junction proteins and may have an impact on BT. These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.

Bacterial Translocation as a Cause of Postoperative Sepsis in Surgical Patients Undergoing Laparotomy

Introduction: Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and the internal organs. Objective of the study is to examine the spectrum of bacteria involved in translocation in surgical patients undergoing laparotomy and to determine the relation between nodal migration of bacteria and the development of postoperative septic complications.&#x0D; Methods: Mesenteric lymph nodes (MLN)culture was done in patients undergoing elective and emergency surgeries fulfilling the inclusion criteria.&#x0D; Results:Bacterial translocation was identified in 22 (44.8%) patients. The most common organism identified was Escherichia coli (n=11, 50%). Both enteric bacteria, typical of indigenous intestinal flora, and non-enteric bacteria were isolated. Postoperative septic complications developed in four (11%) patients. Septic morbidity was more frequent when a greater diversity of bacteria resided within the mesenteric lymph nodes.&#x0D; Conclusion: Bacterial translocation is associated with an increase in the development of postoperative sepsis in surgical patients. The organisms responsible for septic morbidity are similar in spectrum to those observed in the mesenteric lymph nodes. These data strongly support the gut origin hypothesis of sepsis in humans. Besides, there is increased bacterial translocation in patients undergoing emergency procedures.&#x0D; Keywords: bacteria • laparotomy • postoperative • sepsis • translocation

Long-term antibiotics and PPI's induce bacterial translocation in patients with cirrhosis: antibiotics are not always ANTI-biotics.

O’Leary JG, Reddy KR, Wong F, et al. Long-term use of antibiotics and proton-pump inhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2014; pii: S1542-3565(14)01146X. doi: 10.1016/j.cgh.2014.07.060. [Epub ahead of print]. O’Leary et al. (1) prospectively analyzed 188 patients with cirrhosis who were hospitalized for infection from 12 centers (North American Consortium for the Study of End-Stage Liver Disease). They investigated and characterized risk factors for repeat infections in these patients. Patients were followed for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections. Just after 6 months after hospital discharge, only 59% of them were alive and 14% had liver transplant.

Plasma l-citrulline concentrations and its relationship with inflammation at the onset of septic shock: A pilot study

PurposeHypocitrullinemia has been suggested to be a prognostic factor for patients in intensive care. The aim of this ancillary study of the Corticosteroids and Intensive Insulin Therapy for Septic Shock prospective study was to investigate plasma l-citrulline concentrations and its relationship with inflammation and digestive bacterial translocation in patients with septic shock multiorgan failure and without primary intestinal disease or chronic renal failure. MethodsSixteen adult patients were selected. They were studied on day (D) 0 at hours (H) 0, 6, 12, 18, and 24 and on D4 (H96). Selected plasma amino acids and proteins, proinflammatory (tumor necrosis factor α [TNF-α]) and anti-inflammatory (interleukin [IL] 10) cytokine concentrations, and bacterial translocation were measured. ResultsEight D14 survivors and 8 D14 nonsurvivors patients were studied. Citrulline was decreased on D0 (H0: 29 ± 10 vs nadir: 18 ± 6 μmol/L; P < .05). The citrulline nadir was lower (P < .01) in patients with digestive bacterial translocation than that in those without. Mean citrulline concentrations at H0 to H96 were not significantly different between survivors and nonsurvivors. In both groups, citrulline was significantly inversely correlated with C-reactive protein (r2 = 0.10, P < .01) on D0. No significant correlations were found between citrulline and albumin, transthyretin, TNF-α, IL-10, or TNF-α/IL-10 ratio. ConclusionsAt the onset of septic shock, plasma citrulline decreases and varies inversely with C-reactive protein and is lower when digestive bacterial translocation occurs. This finding could reflect an early acute intestinal dysfunction, but measurement of citrulline concentration does not appear to be able to predict the patients' mortality.

1020 POOR AGREEMENT OF DIFFERENT APPROACHES TO ASSESS BACTERIAL TRANSLOCATION IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

1020 POOR AGREEMENT OF DIFFERENT APPROACHES TO ASSESS BACTERIAL TRANSLOCATION IN PATIENTS WITH DECOMPENSATED CIRRHOSIS T. Bruns, P.A. Reuken, A. Vogt, H.W. Zimmermann, A. Stallmach. Division of Gastroenterology, Hepatology and Infectious Diseases, Department of Internal Medicine II, Jena University Hospital, Integrated Research and Treatment Center – Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany; NIHR Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK; Department of Medicine III, University Hospital Aachen, Aachen, Germany E-mail: t.bruns@bham.ac.uk

Probiotics Are Sensitive Microorganisms: Lactobacillus Can Be Affected by Stomach Acid, Antibiotic, and Bowel Cleansing

We read with great interest the article by Mangell et al. entitled ‘‘Lactobacillus plantarum 299v does not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection’’ [1]. The authors show that Lactobacillus plantarum 299v did not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection. Although the study was well presented, there are some limitations and a few points on the affects of probiotics in the study protocol that we would like to address. Bowel cleansing before surgery can change the concentration of gut microbiota. Also, the patients had consumed food with L. plantarum 299v for 8 days in the preoperative period; however in the postoperative period, the patients had consumed L. plantarum 299v without food for 5 days. Foods typically contain fermentable substrates that can help nourish probiotic organisms as they transit through the gastrointestinal tract. Gastric pH following food intake is usually in the range of 4–7. Many lactobacilli and bifidobacteria secrete hydrolytic enzymes that can aid in the digestion of foods. Gastric pH is below 2 in the fasting state, which rapidly kills probiotics [2]. The main factors affecting the viability of probiotics in the gastrointestinal tract are the acidic environment of the stomach and the presence of bile in the duodenum. Significant numbers of probiotic bacteria can be destroyed unless they have some acid protection. Low pH is one of the most important factors that restricts the growth and stability of probiotic bacteria [3, 4]. Recent evidence shows that the dual-coating technology of probiotic bacteria enhances the survival and the amount of bacteria reaching the distal gut [5]. If there is an encapsulation technique of acid protection against L. plantarum 299v, it should be mentioned in this article. Preoperative and postoperative food intake might influence the transit of L. plantarum 299v to the distal gastrointestinal tractus. On the other hand, preoperative antibiotic prophylaxis may alter gut microbiota as well. The detection of bacterial genome in the lymph node does not reliably indicate recent bacterial translocation. Some bacteria might have already translocated in the preprobiotic phase, and scant amounts of these translocated bacteria might not be clinically important. Supporting this hypothesis, the authors did not mention any correlation with bacterial translocation and postoperative septic complications. And finally, two of these patients had translocation of lactobacilli, which is not a pathogenic bacterium. The rate of postoperative complications, although not significant between groups, is markedly decreased in the probiotic group. The overall complication rate, 16 versus 31 % (nearly twice as much in the control group), needs further comment. As a conclusion, probiotics are sensitive microbial agents to various noxious stimuli. Viability of probiotics in gastrointestinal tractus depends on some factors such as gastric acidity, bile acids, enzymes in intestine, antibiotics and bowel cleansing.

169 Markers of Bacterial Translocation in Patients With Chronic Liver Disease

G A A b st ra ct s for HE-related, and all-cause hospitalizations were 0.21 and 0.45 with long term rifaximin use; both rates were significantly lower (p<0.0001, p=0.0051) compared to the corresponding rates for RCT placebo (0.72, 1.31). Safety was not adversely impacted with increased long term rifaximin exposure. Adverse event rates and the rate of change in the mean MELD scores remained stable in the long term. Mortality rates with long term rifaximin exposure were similar between all rifaximin patients (0.1) and the RCT placebo group (0.2) . Conclusions: Long term treatment with rifaximin 550 mg BID afforded continued protection from HE, reduced the hospitalization rate, and did not adversely affect safety or mortality in patients with cirrhosis.