A thermogenic fat-epithelium cell axis regulates intestinal disease tolerance.

Disease tolerance, the capacity of tissues to withstand damage caused by a stimulus without a decline in host fitness, varies across tissues, environmental conditions, and physiologic states. While disease tolerance is a known strategy of host defense, its role in noninfectious diseases has been understudied. Here, we provide evidence that a thermogenic fat-epithelial cell axis regulates intestinal disease tolerance during experimental colitis. We find that intestinal disease tolerance is a metabolically expensive trait, whose expression is restricted to thermoneutral mice and is not transferable by the microbiota. Instead, disease tolerance is dependent on the adrenergic state of thermogenic adipocytes, which indirectly regulate tolerogenic responses in intestinal epithelial cells. Our work has identified an unexpected mechanism that controls intestinal disease tolerance with implications for colitogenic diseases.

Citrobacter braakii bacteremia-induced septic shock after colonoscopy preparation with polyethylene glycol in a critically ill patient: a case report.

BACKGROUND: Polyethylene glycol (PEG) is widely used for bowel cleaning in preparation for colonoscopy because of its safety. Septic shock after PEG preparation is an extremely rare complication. Herein, we describe a case of septic shock that occurred immediately after colonoscopy preparation with PEG. CASE PRESENTATION: A 75-year-old Japanese male who had previously developed diabetes after total pancreatectomy received PEG in preparation for colonoscopy. He had been admitted to the emergency intensive care unit 4 days earlier due to hematochezia presenting with shock. He ingested PEG to prepare for a colonoscopy examination, which was performed to identify the source of his bleeding over a 5-h period, but suddenly exhibited septic shock and markedly elevated procalcitonin levels. A blood culture subsequently revealed Citrobacter braakii. Immediate resuscitation and intensive care with appropriate antibiotics improved his condition. CONCLUSIONS: Clinicians should be aware of the possibility of deteriorating conditions after bowel preparation with PEG among severely ill patients with recent episodes of hemorrhagic shock.

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis.

BACKGROUND: Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). METHOD: Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses. MAIN RESULTS: The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08-2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. CONCLUSIONS: Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients.

High rates of intestinal colonisation with fluoroquinolone-resistant ESBL-harbouring Enterobacteriaceae in hospitalised patients with antibiotic-associated diarrhoea.

The purposes of this study were to investigate the intestinal carriage of extended-spectrum ß-lactamase-harbouring Enterobacteriaceae (ESBL-EN) and associated fluoroquinolone resistance (FQ-R) in 120 hospitalised patients with antibiotic-associated diarrhoea, and to investigate a correlation between Clostridium difficile (C. difficile) infection and intestinal colonisation with ESBL-EN in these patients. Stool samples were screened for C. difficile infection by toxin A/B enzyme-linked immunosorbent assay (ELISA) and for the presence of enterobacterial isolates producing ß-lactamases by plating on ß-lactamase screening (BLSE) agar. Recovered isolates were confirmed pheno- and genotypically for the presence of ESBL genes (bla CTX-M, bla TEM, bla SHV) by the double-disc synergy test and polymerase chain reaction (PCR) sequencing, and tested for the presence of topoisomerase mutations (gyrA, parC) and plasmid-mediated quinolone resistance (PMQR) determinants [qnrA, qnrB, qnrS, qepA, aac(6')-Ib-cr] by PCR sequencing. ESBL-EN were detected in 44/120 (37 %) stool samples. C. difficile-infected patients showed a significantly higher frequency of intestinal colonisation with ESBL-EN compared to C. difficile non-infected patients (62 % vs. 31 %, p = 0.008). Of the 73 ESBL-EN recovered, 46 (63 %) showed high-level FQ-R [ciprofloxacin minimum inhibitory concentration (MIC) ≥32 mg/L]. The largest group consisted of 21 bla CTX-M-15-harbouring Enterobacteriaceae (ciprofloxacin MIC ≥64 mg/L) with multiple topoisomerase mutations in gyrA and parC, in combination with co-carriage of aac(6')-Ib-cr. Most of them were Escherichia coli isolates belonging to sequence types ST131 and ST410. We found remarkably high rates of intestinal colonisation with high-level FQ-R ESBL-EN in hospitalised patients with antibiotic-associated diarrhoea, especially among C. difficile-infected patients. These data underscore the need for stringent infection control to contain this potentially infectious and multidrug-resistant reservoir.

Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses.

Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)(2)D(3) to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)(2)D(3) treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)(2)D(3)-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)(2)D(3)-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)(2)D(3) suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

[Enterobacter cloacae spondylodiscitis through misuse of high-dose intravenous buprenorphine]. / Spondylodiscite à Enterobacter cloacae par mésusage intraveineux de la buprénorphine haut dosage.

INTRODUCTION: We report a case of Enterobacter cloacae spondylodiscitis related to risk practices in intravenous drug addicts (IVDA). OBSERVATION: The patient, a former heroin addict, was receiving long-term, high-dose buprenorphine maintenance treatment. He had been misusing the treatment, injecting it daily for several months. The clinical course included several uncommon features that are usually found in IVDA patients: subacute infection, apyrexia, and minimal inflammatory syndrome. This infection also led to the discovery of his HIV infection. DISCUSSION: Any dorsolumbar pain in IVDA patients, including those receiving regular drug maintenance treatment and especially those with HIV infection, should suggest spondylodiscitis, because of these patients' enhanced sensitivity to infection and the frequent bacteremia caused by persistent or transitory relapse involving injection (exchange of material, reuse of needles, syringes, cotton swabs, and risk of contamination through the hands or saliva).

[Effectiveness of combined vancomycin and pefloxacine in gastrointestinal decontamination for preventing infections after chemotherapy-induced bone marrow aplasia. A randomized double-blind study]. / Intérêt d'associer la vancomycine à la péfloxacine en décontamination digestive pour la prévention des infections après chimiothérapie aplasiante. Etude randomisée en double insu.

OBJECTIVE: To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Oral pefloxacin plus vancomycin (48 patients), pefloxacin alone (51 patients), or placebo (52 patients) were administered in a randomized double-blind study. Evaluation was done by determining site and documentation of infections, organisms responsible for bacteriologically documented infections, organisms acquired in surveillance cultures and number of days with fever during aplasia. RESULTS: Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae. No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive (Gram+) infections and infections with gram-negative (Gram-) organisms usually resistant to pefloxacin. However, placebo gave similar results. There was no induction of resistance to pefloxacin during the study. Tolerance of treatment was excellent. Only a prolonged aplasia has been observed in patients receiving pefloxacin. CONCLUSION: Thus, the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient. The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be questionable.

Oral complications in bone marrow transplantation patients: recent advances.

This paper presents some of the oral aspects encountered in bone marrow transplant (BMT) patients, as reflected in recent research conducted in the Department of Oral Medicine. Oral infections caused by Enterobacteriaceae were found to be responsible for a large proportion of positive cultures, during different stages of the transplantation process. Mucositis was constantly detected concomitant with the infections. It correlated with granulocytopenia and fever. The mucositis improved together with the immune system reconstitution. Immunoglobulins in saliva of BMT patients showed a drastic reduction following the patients' conditioning protocol and a return to normal levels soon after the transplantation. IgA, IgM and IgG were studied. Saliva was also shown to play an important role in the fibrinolytic system, through its plasminogen activator inhibitory contents. It seems that the active molecules are contained in the oral epithelial cells.

Immunosuppression and intestinal bacterial overgrowth synergistically promote bacterial translocation.

Gram-negative, enteric bacilli of the indigenous gastrointestinal tract microflora translocated primarily to the mesenteric lymph nodes in mice given either oral penicillin G sodium or clindamycin hydrochloride. These bacteria also translocated to the mesenteric lymph nodes in mice injected with cyclophosphamide or prednisone. However, in mice treated with the combination of an oral antibiotic plus an immunosuppressive drug, the translocating bacteria spread systemically to the peritoneal cavity. When the treatment with clindamycin and prednisone was extended to 12 days, the mice died of lethal sepsis beginning eight days after treatment. Thus, the combination of intestinal bacterial overgrowth and host immunosuppression synergistically promoted bacterial translocation from the gastrointestinal tract that resulted in lethal sepsis.

[Effect of normal and immune IgG, IgM and IgA on the intestinal microflora of mice with experimental dysbacteriosis]. / Vliianie normal'nykh i immunnykh IgG, IgM, IgA na mikrofloru kishechnika myshei pri éksperimental'nom disbakterioze.

Human IgG, IgM and IgA produce a pronounced protective effect, preventing enterobacteria from penetration into the mucous membrane of the proximal section of the small intestine of mice in antibiotic-induced dysbacteriosis. Normal mouse IgG and IgM, in contrast to IgA, are effective against mucosal enterobacteria of the small intestine. Immune mouse IgG, IgM and IgA show greater activity in protecting the mucous membrane than normal immunoglobulins of these classes.

[Characteristics of experimental antibiotic-induced dysbacteriosis]. / Izuchnie osobennostei antibiotikovogo disbakterioza v éksperimente.

Changes in the microflora of the large and small intestines in mice and guinea pigs after the oral administration of canamycin (a hardly absorbable antibiotic) and ampiox (an easily absorbable antibiotic) in different doses. The administration of these antibiotics in different doses (therapeutic, subtherapeutic and over therapeutic) led to an increase in the number of opportunistic microorganisms and the contamination of the small intestine by these organisms. These changes were also well pronounced in guinea pigs, normally having no enterobacteria. After the administration of the antibiotics was stopped, opportunistic microorganisms were gradually eliminated from the small intestine. The rate of decontamination depended on the administered dose of the antibiotic: the higher the dose was the longer the process of the decontamination of the small intestine lasted. An increase in the amount of opportunistic microbes in the large intestine and the decontamination of the small intestine occurred simultaneously with the decrease in the amount of lactobacilli and bifidobacteria in both the small and large intestines.