Disruption Of Mucosal Integrity Research Articles

PREVOTELLA BIVIA BACTEREMIA POST TOCILIZUMAB IN A PATIENT WITH SEVERE COVID-19 PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Anaerobes generally constitute a major component of the gut microbiome. They play a significant role in the pathogenesis of infections following disruption of mucosal integrity. Anaerobic organisms are usually difficult to grow and identify and hence may often be overlooked. We present a patient with severe COVID-19 pneumonia who developed de-novo Prevotella bivia bacteremia, following tocilizumab. CASE PRESENTATION: A 38 year old Caucasian male with morbid obesity and no other past medical history presented to the emergency department with complaints of cough, fever, chills and poor appetite for the past 10 days. Upon arrival, he was profoundly hypoxic with Spo2 70% on ambient air. He tested positive for COVID-19. On physical examination, his BMI was 62 kg/m2, he was febrile, in moderate respiratory distress, cardiopulmonary examination revealed coarse bilateral breath sounds. His physical examination was otherwise unremarkable. His chest radiograph demonstrated hazy opacification in both mid lungs and left lung base suggestive of multifocal pneumonia. CT chest did not reveal evidence of pulmonary embolism. Lower extremity ultrasound was however negative for a DVT. Laboratory findings was significant for elevated C-reactive protein 12.4 mg/dl. Patient was placed on heated high flow nasal cannula and received dexamethasone and tocilizumab. His respiratory status continued to worsen and he was subsequently intubated. Lower respiratory culture was positive for MSSA and patient was started cefepime and vancomycin was added as he clinically continued to decompensate. Within the next week, blood culture was positive for Prevotella bivia and his antibiotic regimen was changed to pipericillin-tazobactam. Repeat blood culture continued to be positive and this time, for Enterococcus faecalis. The antibiotic regimen was further changed to meropenem. Interestingly, on his physical examination, there was no abnormalities on his abdomen or pelvic area. CT abdomen pelvis did not shows any acute abnormalities. Following meropenem initiation, his subsequent blood cultures have been negative for any growth. Patient remains intubated with a guarded prognosis. DISCUSSION: Prevotella bivia is one of several species of bacteria in the genus Prevotella. It is an anaerobic gram negative organism that is found in the oral, vaginal, and gut microbiome. Some of the infections caused by this organism include aspiration pneumonia, lung abscess, otitis media, and sinusitis. Various species of Prevotella have been isolated from abscesses and burns close of the mouth, bite, paronychia, urinary tract infection, brain abscess, osteomyelitis, and bacteremia when there is an associated respiratory tract infections. Prevotella bivia bacteremia is highly uncommon. CONCLUSIONS: As we continue to learn more about COVID-19 infection and its treatment modalities, we may come across such unusual scenarios. REFERENCE #1: 27.Curtis JR, Perez-Gutthann S, Suissa S, et al. Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. Semin Arthritis Rheum 2015;44:381. REFERENCE #2: Yanagisawa M, Kuriyama T, Williams DW, Nakagawa K, Karasawa T. Proteinase activity of prevotella species associated with oral purulent infection. Curr Microbiol. 2006;14(5):375–378. doi: 10.1007/s00284-005-0261-1 REFERENCE #3: Metronidazole Resistance in Prevotella spp. and Description of a New nim Gene in Prevotella baroniaeC. Alauzet, F. Mory, C. Teyssier, H. Hallage, J. P. Carlier, G. Grollier, A. Lozniewski DISCLOSURES: No relevant relationships by Alfred Aiyanyor, source=Web Response No relevant relationships by Navitha Ramesh, source=Web Response No relevant relationships by Q. Kamran Uddin, source=Web Response

Evaluation of oropharyngeal infections in febrile neutropenic patients: a study of 335 episodes

Objective In neutropenic patients, mucositis can occur in the entire gastrointestinal tract, especially in the oropharynx. Disruption of mucosal integrity provides the basis for local invasion and causes it to become an important focus of infection. The aim of this study was to draw attention to the importance of oral cavity examination and evaluation of oropharyngeal infections in patients with febrile neutropenia (FN).Methods Demographic data, number of episodes, distribution of malignancies and developing oropharyngeal infections of febrile neutropenic patients with hematologic malignancies in a tertiary hospital over a three-year period were evaluated.Results A total of 170 patients with 335 FN episodes were included in our study. Bacteremia was the most common microbiologically documented infection (n=92, 27.5%). the second most common infection was oropharyngeal infections (n=69, 20.1%). The most common microorganism isolated from oropharyngeal infections was fungi (n=34, 49.3%).Conclusions Oropharyngeal infections of febrile neutropenic patients may cause localized and systemic infections. Daily examination and care of the oral cavity of the patients should be done with care. The oropharyngeal flora should be closely monitored and it should be considered that the flora may also be a source in case of a possible infection.

Study of the action of nanostructured sapropel at different doses on the morphological and functional condition of the gastrointestinal tract in albino mice

A nanostructured sapropel with a particle size of 45.0–180.0 nm has been manufactured by ultrasonic impact on sapropel. While studying its acute oral toxicity in albino mice, a safe dose of 0.3 g/kg of body weight is determined. A single intragastric administration at doses of 1.2, 1.8, and 2.4 g/kg of body weight reveals a dose-dependent character of intoxication symptoms. A dose of 3.0 g/kg of body weight is sublethal. During a diagnostic autopsy of mice treated with nanostructured sapropel at a dose of 0.3 g/kg, we observed the enhancement of physiological processes of the secretory activity in the gastrointestinal tract. Histological examination shows a moderate secretion of mucus and the integrity of the surface epithelial cells of the esophagus, stomach, and duodenum. Acute catarrhal inflammation of the esophagus, stomach, and duodenum is observed in mice that receive the preparation at a dose of 1.8 g/kg. A focal deformation of the surface epithelial cells with the preservation of their cytology and adhesion of the sapropel conglomerates by mucus are revealed by microscopic examination. Catarrhal-hemorrhagic esophagitis, gastritis, and duodenitis are observed in mice treated with the nanostructured sapropel at a dose of 3.0 g/kg. During a histological examination of the gastrointestinal tract in the areas of contact with nanostructured sapropel, thinning and disruption of mucosal integrity, desquamation, and lysis of epithelial cells are found.

Pathogenic potential of Saccharomyces strains isolated from dietary supplements.

Saccharomyces cerevisiae plays a beneficial role in health because of its intrinsic nutritional value and bio-functional properties, which is why it is also used as a dietary supplement. However, the perception that S. cerevisiae is harmless has changed due to an increasing number of infections caused by this yeast. Given this scenario, we have tested whether viable strains contained in dietary supplements displayed virulence-associated phenotypic traits that could contribute to virulence in humans. We have also performed an in vivo study of the pathogenic potential of these strains using a murine model of systemic infection by intravenous inoculation. A total of 5 strains were isolated from 22 commercial products and tested. Results highlight one strain (D14) in terms of burden levels in brains and kidneys and ability to cause death, whereas the other two strains (D2 and D4) were considered of low virulence. Our results suggest a strong relationship between some of the virulence-associated phenotypic traits (ability to grow at 39°C and pseudohyphal growth) and the in vivo virulence in a mouse model of intravenous inoculation for isolates under study. The isolate displaying greatest virulence (D14) was evaluated in an experimental murine model of gastrointestinal infection with immunosuppression and disruption of mucosal integrity, which are common risk factors for developing infection in humans, and results were compared with an avirulent strain (D23). We showed that D14 was able to spread to mesenteric nodes and distant organs under these conditions. Given the widespread consumption of dietary supplements, we recommend only safe strains be used.

Longitudinal Analysis of Distribution and Function of Plasmacytoid Dendritic Cells in Peripheral Blood and Gut Mucosa of HIV Infected Patients

Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.

Abstract LE01: DISTINGUISHED LECTURE ON TARGETS FOR CANCER PREVENTION: Prevention of cervical cancer in current and future generations by HPV vaccination and other approaches

Abstract LE01: <b>DISTINGUISHED LECTURE ON TARGETS FOR CANCER PREVENTION:</b> Prevention of cervical cancer in current and future generations by HPV vaccination and other approaches

Recent advances in the management of fungal infections.

The treatment of cancer has undergone many advances in recent years, leading to significant increases in patient survival. Improvements have come not only in the therapies themselves, but also in our ability to sustain critically ill patients. This, in turn, has allowed more intensive cytotoxic chemotherapies and an increased application of bone marrow transplantation for a broader range of neoplasms. More aggressive chemotherapy regimens have led to more profound immunosuppression and increased risk of infection. Longer survival in more critically ill patients, as well as the relative success of antibacterial therapies, have contributed to a dramatic increase in the incidence of invasive fungal disease among oncology patients. Additional risk factors for fungal infection, common in cancer patients, include the interruption of natural protective barriers by indwelling intravascular catheters, extensive surgical procedures, and chemotherapy-induced disruption of mucosal integrity.

Polyamines attenuate jejunal mucosal injury induced by oleic acid.

Effects of putrescine, spermidine, and spermine on lipid-induced injury to jejunal mucosa were assessed in anesthetized rats. Mucosal epithelial integrity was continuously monitored by measuring blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of jejunal lumen with emulsified lipid (20 mM sodium taurocholate and 40 mM oleic acid) increased 51Cr-EDTA clearance. Addition of spermidine (0.5 mM), but not putrescine (2.0 mM) or spermine (0.25 mM), to the lipid perfusate reduced the increment in 51Cr-EDTA clearance. Histological evaluation of jejunal mucosa indicated that the epithelial lining of the villous tips was damaged by emulsified oleic acid and that this injury was ameliorated by spermidine. Pretreatment of jejunal mucosa with spermidine did not prevent disruption of mucosal integrity induced by a subsequent perfusion with emulsified lipids. Intravenous infusion of spermidine to achieve an extracellular concentration of 0.5 mM did not prevent the lipid-induced increase in 51Cr-EDTA. Spermidine also ameliorated lipid-induced disruption of Caco-2 cell monolayers in culture; this protective effect was dose dependent and was observed only when spermidine was applied to the apical aspect of the monolayers. These findings indicate that spermidine must be present on the apical portion of the epithelial cell during lipid insult. Substitution of lysine or arginine for spermidine did not reduce the extent of lipid-induced injury to jejunal mucosa, indicating that spermidine's protective effects cannot simply be attributed to its cationic nature. Spermidine did not alter the turbidity of a micellar oleic acid solution, indicating that spermidine was not removing oleic acid from the soluble phase.(ABSTRACT TRUNCATED AT 250 WORDS)