Spontaneous Bacterial Translocation Research Articles

A CASE REPORT OF SYNCHRONOUS MULTIFOCAL NECROTIZING FASCIITIS DUE TO CLOSTRIDIUM SEPTICUM IN AN IMMUNOCOMPROMISED HOST

A CASE REPORT OF SYNCHRONOUS MULTIFOCAL NECROTIZING FASCIITIS DUE TO CLOSTRIDIUM SEPTICUM IN AN IMMUNOCOMPROMISED HOST

Treatment for cirrhotic ascites

Common complications of decompensated liver cirrhosis are esophageal varices, hepatic encephalopathy and ascites. After the onset of complications, the prognosis worsens. In patients with ascites, the 5-year mortality rate is 44%. Furthermore, hyponatremia, spontaneous bacterial translocation and hepatorenal syndrome also greatly worsen the prognosis. Effective treatment of cirrhotic ascites improves the quality of life and survival rate. Recently, the newly produced diuretic, tolvaptan (vasopressin V2 receptor antagonist), was reported to be effective in the treatment of refractory ascites in liver cirrhosis; however, there has not been an associated positive effect on the prognosis. There are various types of treatment for ascites, such as large-volume paracenteses, a cell-free and concentrated ascites reinfusion therapy, a transjugular intrahepatic portosystemic shunt, and a peritoneo-venous shunt. Although they improve the prognosis, liver transplantation remains the ultimate form of treatment. The present article discusses the therapeutic management of cirrhotic ascites.

Mitigation of bacterial translocation and subsequent sepsis in γ-irradiated mice treated with CCL1 antisense ODN (INC4P.331)

Abstract Gut bacteria-associated sepsis is a serious concern in persons who have radiation-induced injuries in the gastrointestinal system. Such infection does not normally occur in healthy hosts with M1Mϕ. However, M1Mϕ are not generated in γ-irradiated mice (WBI-mice), even though Mϕ are still present. WBI-mice are carriers of M2bMϕ, which inhibit Mϕ conversion from resident Mϕ to M1Mϕ. We have previously reported that sepsis stemming from Enterococcus faecalis oral infection is markedly mitigated in 5 Gy WBI-mice after M2bMϕ polarization using CCL1 antisense ODN. In this study, we examined the effect of CCL1 antisense ODN on spontaneous bacterial translocation and subsequent sepsis in 8 Gy WBI-mice. The ODN was administered (s.c., twice daily) to 8 Gy WBI-mice for 1 week starting 3 days after γ-irradiation. The efficacy of the treatment was evaluated by an increase in the percentage of survival in test groups, as compared with that of control groups. All control mice died within 22 days of γ-irradiation. However, 70% of the WBI-mice treated with 25 to 125 μg/mouse of the ODN survived more than 30 days after γ-irradiation. Severe bacteremia and bacterial growth in MLNs were not seen in WBI-mice treated with the ODN. M1Mϕ were isolated from MLNs of these mice, while M2bMϕ were not. These results indicate that the Mϕ polarization therapy using CCL1 antisense ODN is effective to mitigate spontaneous bacterial translocation and subsequent sepsis in mice exposed to 8 Gy of γ-irradiation.

Spontaneous Enterobacter Cloacae Pyogenic Liver Abscess

Introduction: Pyogenic liver abscess is associated with significant morbidity and mortality. The overall case fatality rate for pyogenic liver abscess is 5.6%. The incidence of pyogenic liver abscess in North America has steadily increased over the past decade, is currently estimated to be 2.3 cases per 100,000, and is higher among men than women. Case Report: A 51-year-old white female with past medical history of hypertension presented to the primary care clinic with a 2-week history of abdominal pain and generalized malaise. She denied any history of recent travel, intravenous drug abuse, alcoholism, recent surgical or endoscopic procedures. She was noted to be febrile, and abdominal examination revealed right upper quadrant tenderness. She was then transferred to the emergency department, where laboratory work-up revealed an elevated white blood cell count of 18 x 109 cells. Contrast enhanced computerized tomographic (CECT) scan of the abdomen showed multiple peripherally enhancing lesions in both lobes of the liver, suggestive of multiple liver abscesses. The largest collection measuring 7 cm in the right posterior lobe was drained using a CT guided pig tail catheter insertion. Gram stain and culture of the aspirate grew Enterobacter cloacae. She was treated with intravenous piperacillin-tazobactam for 4 weeks, followed by oral levofloxacin and metronidazole for another 4 weeks. Follow-up evaluation at 6 weeks after treatment completion showed complete radiographic resolution. Discussion:Enterobacter cloacae is a gram-negative, facultative anaerobic, rod-shape bacteria found as a normal gut flora in many human beings. In the U.S., the more commonly identifiable organisms in patients with pyogenic liver abscess are E.coli and Streptococcus species. However, Asian and African countries report a higher prevalence of parasitic and Klebsiella infections. Enterobacter cloacae infections are commonly seen in patients with an underlying hepato-biliary or pancreatic disease, recent surgical procedure, or with an underlying malignancy, especially colon cancer. To our knowledge, this is the first reported case of Enterobacter cloacae infection causing a clinically significant pyogenic liver abscess in a patient with no identifiable risk factors. The exact mechanism of the spread of this organism is uncertain, but spontaneous bacterial translocation seems to be the most likely explanation. This is particularly worrisome, as significant antimicrobial resistance exists within this group of species. Our patient was treated with a CT-guided drainage in combination with prolonged antibiotics in a relatively large size abscess (>5 cm) with good outcome and avoiding a surgical intervention.

Effect of CCL1 antisense ODN on spontaneous bacterial translocation and subsequent sepsis in mice irradiated with whole body 137Cs γ-rays (WBI-mice) (INC7P.412)

Abstract Radiation victims who suffer from gastrointestinal injuries are extremely susceptible to gut-associated sepsis. In our previous studies, M1Mφ located in the lamina propria and mesenteric lymph nodes were shown to be major effector cells against bacterial translocation. However, M1Mφ were not generated in these organs of WBI-mice who are carriers of M2bMφ (inhibitor cells for Mφ conversion from resident Mφ to M1Mφ). CCL1 produced by M2bMφ is essential for the maintenance of M2bMφ properties. In this study, we examined the effect of CCL1 antisense ODN on gut-associated sepsis stemming from endogenous intestinal microflora in 9 Gy WBI-mice. CCL1 antisense ODN was administered s.c. to WBI-mice twice a day for 1 week starting 3 days post-exposure to γ-rays. This group of mice was designated as treated mice. The mortality rates and bacterial growth in the organs and blood of treated mice were compared to those of control mice (WBI-mice treated with scrambled ODN). In the results, control mice died within 14 days of γ-irradiation, while 30% of treated mice survived more than 30 days after the irradiation. Bacteria progressively grew in the mesenteric lymph nodes, liver and blood of control mice, while the pathogens were not isolated significantly from these organs of treated mice. These results indicate that sepsis stemming from spontaneous bacterial translocation is noticeably mitigated in WBI-mice treated with CCL1 antisense ODN.

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Effect of prenatal cortisone on spontaneous bacterial translocation from gastrointestinal tract in neonatal rat.

The immature host is prone to the passage of bacteria across the gut mucosal barrier. Corticosteroids accelerate the maturation of the intestinal mucosa and alter the composition of the gut bacterial flora. The present study was performed to assess the effect of prenatal cortisone on bacterial translocation in the neonatal rat. Time-pregnant Sprague Dawley rats were randomized on the 19th day of gestation for intraperitoneal injection of either 20 mg/100 g body weight of hydrocortisone or saline. Rats delivered spontaneously and the offspring were suckled ad libitum by the dam. Rat pups (N = 82) were killed 1 or 9 days after delivery. Mesenteric lymph nodes, liver, heart blood, and the terminal ileal loop were excised and quantitatively analyzed for bacteria. After one day, the proportion of rats with positive translocation was not significantly different between the two treatment groups (saline 62%, cortisone 80%, P = NS). By day 9, translocation had increased in the saline group (P = 0.03 vs day 1), did not significantly change in the cortisone group, and was significantly lower in rats treated with cortisone compared with the saline control (saline 90%, cortisone 60%, P = 0.02). The decrease in bacterial translocation after treatment with cortisone was associated with significantly lower total bacterial counts in the ileum (P < 0.05). Cortisone did not reduce bacterial counts in extraintestinal organs with positive translocation. In conclusion, prenatal treatment with cortisone reduces the incidence of spontaneous bacterial translocation from the intestine but not the concentration of translocated bacteria in extraintestinal organs of 9-day-old rats. Cortisone-induced changes of the intestinal microflora may have contributed to the reduction in translocation frequency.

Time course of spontaneous bacterial translocation from gastrointestinal tract and its relationship to intestinal microflora in conventionally reared infant rats.

Whereas the developed gut mucosal barrier prevents luminal bacteria from invading the host, bacterial translocation appears to be facilitated in the neonate. The aim of this study was to determine the extent to which bacteria spontaneously translocate from the gut to extraintestinal organs during the neonatal period and to relate translocation to the evolving intestinal flora in the rat. Newborn Sprague-Dawley rats suckled ad libitum and ate regular chow after weaning. A total of 167 rats were killed either immediately or at 1, 9, 14, 21, 26, or 42 days after delivery. Mesenteric lymph nodes (MLN), liver, heart blood, and the terminal ileal loop were harvested under sterile conditions and analyzed for aerobic and facultatively anaerobic bacteria by standard microbiologic procedures. Bacterial translocation to the MLN and liver began soon after birth and peaked during the second week. On day 14, translocation to any organ was present in 85% of rats. All cultures from the liver were sterile after day 26. By contrast, the fall in translocation to the MLN was incomplete, as 50% of pups still had positive MLN on day 42. Blood cultures were positive in three of the 167 rats. The intensity of translocation as determined by the number of organs infected significantly increased with the number of gram-negative enterics and gram-positive cocci in the gut and was negatively correlated with the percentage of lactobacilli from the total measured intestinal flora (P < 0.0001). In conclusion, bacterial translocation from the gut is a physiological and age-dependent phenomenon in the neonatal rat. Translocation appears to be facilitated when intestinal concentrations of gram-negative enterics and gram-positive cocci are high and when the concentration of lactobacilli is low.

Confirmation of Translocated Gastrointestinal Bacteria in a Neonatal Model

Purpose. The hypothesis that enteric bacteria translocate from the gastrointestinal (GI) tract to extraintestinal sites has been extensively studied. However, definitive evidence that spontaneous bacterial translocation and dissemination from the GI tract to extraintestinal sites occur in a neonatal model has been lacking. The aim of this study was to confirm this phenomenon by tracking enterally administered, plasmid-labeled bacteria to extraintestinal sites.Materials and Methods. Escherichia coli 07:K1 (E. coli K1) with and without a nontransferable, ampicillin resistance plasmid (pGEM-7) were used in this study. Newborn New Zealand white rabbit pups were separated into three treatment groups: transformed E. coli K1 (E. coli K1 + pGEM-7, n = 20), nontransformed E. coli K1 (n = 12), and control pups (no bacteria, n = 7). Pups were enterally fed 10% Formulac solution supplemented with a suspension of bacteria respective to their group. After the pups fed twice daily for 2 days, representative tissue specimens from the small bowel (SB), mesenteric lymph nodes (MLNs), spleen (SPL), and liver (LIV) were aseptically harvested and tested for culture growth in ampicillin-supplemented medium.Results. Positive growths of plasmid-induced ampicillin-resistant bacteria were detected in tissue specimens harvested from rabbits fed transformed E. coli K1, but were not detected in the other groups.Conclusion. This experiment demonstrated conclusively that transformed E. coli K1 fed to healthy rabbit pups spontaneously translocated from the intestinal lumen and subsequently disseminated to the mesenteric lymph nodes, spleen, and liver.

The effect of epidermal growth factor on bacterial translocation in newborn rabbits

Purpose: Epidermal growth factor (EGF), which is present in breast milk, has both trophic and maturational effects on intestinal mucosa. The aim of this study is to deermine the effect of EGF on spontaneous intestinal bacterial translocation (BT) in formula-fed newborn rabbits, who have a high incidence of BT compared with breast-fed newborn rabbits. Methods: Sixty-one rabbit pups were divided into three groups: EGF(−), n = 24, EGF(+), n = 22, and breast-fed animals, n = 15. Both the EGF(−) and EGF(+) groups were gavage fed a standard artificial formula three times daily. EGF was administered subcutaneously three times daily (1.5 μg/g body weight per day) in the EGF(+) group. The breast-fed group was fed by their mothers ad libitum. At 7 days of age, all rabbits were killed, and the mesenteric lymph nodes (MLN), liver, and spleen were cultured qualitatively for bacterial growth, while the cecum and ileum were quantitatively cultured. To determine the effect of EGF on mucus-producing cells, goblet cell numbers in the small intestine were quantified histologically. Results: There was no BT to MLN, spleen, or liver in the breast-fed group. The incidence of BT to MLN and spleen was significantly lower in the EGF(+) compared with EGF(−) group; (EGF[+]: MLN, 45%; spleen, 32%; Liver, 27%; EGF[−]: MLN, 79%; Spleen 67%; Liver 29%; in EGF[+] MLN and Spleen P < .05 v EGF[−]). There was no significant difference in cecal and ileal bacterial colonization between the EGF(+) and EGF(−) groups. The number of goblet cells in the small intestine was significantly lower in the EGF(−) group compared with the EGF(+) group as follows: EGF(+), 14 ± 3; EGF(−), 9 ± 3; breast-fed, 11 ± 5 goblet cells per 100 epithelial cell nuclei; P = .013. Conclusions: (1) EGF caused a significant decrease in spontaneous bacterial translocation in formula-fed newborn rabbits and was associated with an increase in the goblet cell number of the small intestine. (2) These changes occurred in spite of the fact that no changes in small bowel bacterial colonization were observed. (3) These results suggest, but do not prove, that EGF may provide protection for neonates from gut origin infection by improving the mucosal barrier function through increased goblet cell production, thus decreasing the incidence of spontaneous bacterial translocation in the newborn.

Intestinal permeability to small- and large-molecular-weight substances in the newborn rabbit

Background/Purpose: The authors have previously reported the occurrence of spontaneous bacterial translocation (BT) and its resolution with age in the newborn rabbit. They have also reported a close correlation between small bowel bacterial colonization (BC-SB) and BT at 1 week of age, suggesting that the presence of luminal bacteria and their production of endotoxins may increase the intestinal permeability. The aim of this study was to evaluate intestinal permeability to small and large molecules in the newborn rabbit and to correlate it with BT. Materials and Methods: New Zealand White rabbits (n = 96) 1, 7, 14, 21, and over 120 days (adult) of age were given either C 14-labeled ethylene diamine tetraacetic acid (EDTA) (MW 290) or C 14-Dextran (MW 70,000) via an orogastric tube at 1 mCi per 100 g of body weight. Five hours later, blood, urine, liver, and intestine were collected, and scintillation counting was performed after solubilization. In a separate series of rabbits (n = 136), the incidence of BT, BC-SB, and small intestinal surface area (SA) were measured. Results: Total permeability to Dextran decreased with age and was significantly reduced at 14 days of age. In contrast, total permeability to EDTA increased and was maximal in 7-to 14-day-old rabbits and began to decrease at 21 days of age. The incidence of BC-SB rapidly increased at 7 days of age and reached 100% at 14 days of age. The incidence of BT peaked at 7 days of life (30%) and then decreased with age. SA increased rapidly in the first 3 weeks and SA growth rate of 21-day-old rabbits was almost 1,400% compared with 1-day-old rabbits. Conclusions: This study has shown an age-related reduction of intestinal permeability to large (Dextran) and small (EDTA) molecular weight particles. However, intestinal permeability to EDTA had a different pattern than Dextran, suggesting that there may be different mechanisms of intestinal permeability to different size molecules. Intestinal permeability to EDTA closely correlated with bacterial colonization and bacterial translocation, suggesting that changes in the intestinal bacterial environment may affect the intestinal permeability, possibly by activating the immune system secondary to increases in endotoxins and bacteria.

The association of gut-associated lymphoid tissue and bacterial translocation in the newborn rabbit

The authors have previously demonstrated spontaneous bacterial translocation (BT) in newborn rabbits and its resolution with aging. It is hypothesized that this spontaneous BT was associated with an immature gut-associated lymphoid tissue (GALT). The aim of the present study was to characterize the cellular populations of the GALT in rabbits at various ages and to correlate this with the frequency of BT. Small bowel (SB) sections and mesenteric lymph nodes (MLN) were harvested and cultured (aerobically) from New Zealand White rabbits at 0, 6, 14, 28, and more than 90 days of age for determination of bacterial colonization (BC) and BT. Portions of ileum (n = 6 for each age) were simultaneously harvested for immunoperoxidase staining. Total T cells (CD5 +), expressed as the number of positive cells/1,000 nuclei and activated T cells (CD25 +), expressed as the number of positive cells/1000 nuclei and as the ratio of CD25 + CD5 + cells, were analyzed for each tissue. Positive cells were counted in 30 villi by light microscopy. The incidence of BT rose as BC increased in the small bowel and peaked at 6 days of age; BT then decreased with age. CD5 + cells in the small bowel villi at 0 days of age were few (2.5 positive cells/1000 nuclei) and the number significantly increased with age (6 days, 6.5; 14 days, 19.0; 28 days, 31.6; adult, 136.6 positive cells/1,000 nuclei). The distribution of T cells started in the crypts, and with advancing age, cells were found all the way to the top of the villi. The number of CD25 + cells in the villi increased with age. The CD25 + CD5 + ratio in the small bowel villi peaked at 6 days of age. These results demonstrate an inverse relationship between the number of CD5 + cells in the intestinal villi and the incidence of bacterial translocation. The elevation of activated T cells (CD25 +) at 6 days of age may be the result of an immunologic activation during the time of peak bacterial translocation. These data suggest that maturity of the GALT leads to a loss of spontaneous bacterial translocation in the newborn period. Modalities that supplement the GALT may help reduce bacterial translocation.

Acute hypoxia does not increase bacterial translocation in newborn rabbits

Purpose: We have previously demonstrated that spontaneous bacterial translocation (BT) occurs, in newborn rabbits and correlates strongly with small bowel colonization (BC). Birth stress, specifically hypoxia, is believed to increase this pathologic process and thus lead to sepsis. This study investigated the relationship between BT and acute hypoxia in newborn rabbits. Methods: Four hundred seventeen rabbit pups (aged 0, 2 to 4, 6, and 28 days) were divided into four groups according to the type of hypoxic stress: 9% O 2 for 1 hour, 9% O 2 + 12% CO 2 for 1 or 4 hours, and 21% O 2 (control animals). The animals were killed 1.5 or 20 hours after the stress. Sterile specimens of mesenteric lymph nodes (MLN), spleen, liver, small bowel, and large bowel were incubated aerobically at 37°C for 24 hours in thioglycolate broth, and subsequently plated on both MacConkey and Colistin Naladixic Acid media. After 24 hours, the growth on both plates was recorded. χ 2 analysis was used, and P values of less than .05 were considered significant. Results: BC of the small bowel and BT to the MLN were low in the first 4 days of life in the hypoxic groups (range, 0% to 21% BC, 0% to 6% BT) and the control group (range, 4% to 30% BC, 3% to 12% BT). After an increase in BC at 6 days of age, the rate of BT increased to 25% to 29% in control animals. The rate of BT in the hypoxic groups (25%) did not differ significantly from that of the controls ( P > .05). Additionally, killing at 20 hours ( v 1.5 hours) was not associated with an increase in the incidence of BT. None of the stress groups had a significant increase in BT compared with the controls. Importantly, although 4 hours of 9% O 2 + 12% CO 2 resulted in a 30% mortality rate, the incidence of BT was no higher than that of the control animals (13% v 29%; P > .05). Conclusion: Severe hypoxic stress in newborn rabbits does not increase the incidence of BT. Because the incidence of BT correlates with that of BC, and because BC is the same in the control and hypoxic animals, the sepsis observed in hypoxic newborns probably is not related to an increased incidence of BT.

Time course of spontaneous bacterial translocation in the neonatal rat

Time course of spontaneous bacterial translocation in the neonatal rat

Colonization of intestinal bacteria in the normal neonate: Comparison between mouth and rectal swabs and small and large bowel specimens

Seventy-four New Zealand white rabbit pups were divided into four groups: group I, 2 days of age (n = 9); group II, 3 to 5 days of age (n = 24); group III, 6 to 8 days of age (n = 27); and group IV, 10 to 13 days of age (n = 14). Mouth swabs (MS), rectal swabs (RS), small bowel specimens (SB), and large bowel specimens (LB) were obtained from each rabbit, incubated for 24 hours in thioglycolate broth, and plated on blood agar in aerobic and anaerobic environments. After 24 hours, growth on blood agar plates were observed. All MS specimens and all but one RS specimen showed positive growth. Growth of both LB and SB specimens increased significantly with age ( P < .04). In addition, SB growth was significantly less than RS or MS growth in groups I, II, and III ( P < .05). LB growth was significantly less than RS or MS growth in group I ( P < .01) and tended to be less in groups II and III (62.5% v 100% and 93% v 100%, respectively). These data show that nearly half of normal rabbits under 6 days of age have sterile small and large intestines despite almost 100% growth from rectal and mouth swabs. These findings partially explain the absence of spontaneous bacterial translocation in young rabbit pups (under 4 days of age) and have important implications for the prophylaxis and treatment of neonatal sepsis.

Bacterial translocation in the neonate

Bacterial translocation has been a major topic of investigation for the past two decades. Despite recent evidence that bacterial translocation may play a significant role in the morbidity and mortality of adults faced with multiple types of stress, very little is known about the effect of bacterial translocation on the neonate. Recently more and more evidence has suggested that normal as well as premature or ill neonates experience spontaneous bacterial translocation quite commonly. This article reviews the recent literature on bacterial translocation in stressed adults, the development of an intact intestinal mucosal barrier in the newborn as a protection against bacterial translocation, and the role of spontaneous bacterial translocation in the development of systemic sepsis and its accompanying morbidity and mortality.

Elemental diet alters macrophage function in mice

Administration of a chemically defined liquid elemental diet (ED) induces spontaneous bacterial translocation to mesenteric lymph nodes (MLN) in animal models. The influence of this process on host immunity is unclear. This study evaluated the effects of ED on peritoneal macrophage (PMφ) antimicrobial functions. Conventional C57/BL6 mice and endotoxin-resistant C3H/HeJ mice ( n = 60) were randomized to be pair-fed either an ED or regular chow diet (RD) for 14 days. Blood, spleen, liver, and MLN were cultured for bacteria. PMφ were harvested for: percentage Candida albicans (CA) phagocytosis, percentage killing of CA, PMφ superoxide anion (O2 −) production, and TNF-dependent macrophage cytotoxicity. Enteral feeding of ED in conventional C57/BL6 mice caused significant bacterial translocation to MLN but not other organs. Significant impairment of CA killing by PMφ occurred in the ED group and was associated with reduced O2 − production. Tumor necrosis factor (TNF)-dependent cytotoxicity of PMφ was also decreased. In endotoxin-resistant C3H/HeJ mice, bacterial translocation was not observed and PMφ antifungal functions remained similar in both RD and ED groups. Thus, enteral feeding of an elemental diet downregulates host oxidative and antimicrobial mechanisms and TNF-dependent cytotoxicity in conventional mice which may be secondary to elemental diet-induced bacterial translocation.