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https://www.readbyqxmd.com/read/29331267/identification-and-initial-optimization-of-inhibitors-of-clostridium-difficile-c-difficile-toxin-b-tcdb
#1
Jeffrey J Letourneau, Ilana L Stroke, David W Hilbert, Laurie J Sturzenbecker, Brett A Marinelli, Jorge G Quintero, Joan Sabalski, Linh Ma, David J Diller, Philip D Stein, Maria L Webb
The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) is described. A high throughput screening (HTS) campaign resulted in the identification of moderately active screening hits 1-5 the most potent of which was compound 1 (IC50 = 0.77 µM). In silico docking of an early analog offered suggestions for structural modification which resulted in the design and synthesis of highly potent analogs 13j(IC50 = 1 nM) and 13 l(IC50 = 7 nM) which were chosen as leads for further optimization...
January 5, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29331160/reduction-in-rate-of-nosocomial-respiratory-virus-infections-in-a-children-s-hospital-associated-with-enhanced-isolation-precautions
#2
Lorry G Rubin, Nina Kohn, Susan Nullet, Margaret Hill
OBJECTIVE To determine whether the use of enhanced isolation precautions (droplet and contact precautions) for inpatients with respiratory tract viral infections is associated with a reduction in rate of nosocomial viral respiratory infections. DESIGN Quasi-experimental study with the rate of nosocomial respiratory virus infection as the primary dependent variable and rate of nosocomial Clostridium difficile infection as a nonequivalent dependent variable comparator. SETTING Cohen Children's Medical Center of NY, a tertiary-care children's hospital attached to a large general hospital...
January 14, 2018: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/29329918/trends-in-incidence-of-long-term-care-facility-onset-clostridium-difficile-infections-in-10-us-geographic-locations-during-2011-2015
#3
Alice Y Guh, Yi Mu, James Baggs, Lisa G Winston, Wendy Bamberg, Carol Lyons, Monica M Farley, Lucy E Wilson, Stacy M Holzbauer, Erin C Phipps, Zintars G Beldavs, Marion A Kainer, Maria Karlsson, Dale N Gerding, Ghinwa Dumyati
During 2011-2015, the adjusted long-term-care facility onset Clostridium difficile infection incidence rate in persons aged ≥65 years decreased annually by 17.45% (95% confidence interval, 14.53%-20.43%) across 10 US sites. A concomitant decline in inpatient fluoroquinolone use and the C difficile epidemic strain NAP1/027 among persons aged ≥65 years may have contributed to the decrease in long-term-care facility-onset C difficile infection incidence rate.
January 9, 2018: American Journal of Infection Control
https://www.readbyqxmd.com/read/29329346/evaluation-of-bloodstream-infections-clostridium-difficile-infections-and-gut-microbiota-in-pediatric-oncology-patients
#4
Bryan T Nycz, Samuel R Dominguez, Deborah Friedman, Joanne M Hilden, Diana Ir, Charles E Robertson, Daniel N Frank
Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in pediatric oncology/hematology/bone marrow transplant (BMT) populations are associated with significant morbidity and mortality. The objective of this study was to explore possible associations between altered microbiome composition and the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool samples were collected from all patients admitted to the pediatric oncology floor from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by bacterial 16S rRNA gene profiling...
2018: PloS One
https://www.readbyqxmd.com/read/29324599/risk-factors-incidence-and-morbidity-associated-with-obstetric-clostridium-difficile-infection
#5
Jacob Ruiter-Ligeti, Sophie Vincent, Nicholas Czuzoj-Shulman, Haim Arie Abenhaim
OBJECTIVE: To evaluate the risk factors, incidence, and morbidity associated with the diagnosis of obstetric Clostridium difficile infection. METHODS: We performed a retrospective cohort study on women admitted for delivery using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from the United States. The delivery admission records of pregnant women were reviewed between 1999 and 2013. After adjusting for demographic and clinical characteristics, we assessed risk factors for the diagnosis of C difficile infection using unconditional logistic regression...
January 9, 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29321041/effects-of-stress-ulcer-prophylaxis-in-adult-icu-patients-receiving-renal-replacement-therapy-sup-icu-renal-siren-study-protocol-for-a-pre-planned-observational-study
#6
Joerg C Schefold, Anders Perner, Theis Lange, Jørn Wetterslev, Matt P Wise, Mark Borthwick, Stepani Bendel, Frederik Keus, Anne Berit Guttormsen, Søren Marker, Mette Krag, Morten Hylander Møller
BACKGROUND: Proton pump inhibitors are often used in critically ill patients to prevent gastrointestinal bleeding despite limited evidence for benefit. Patients with acute kidney injury requiring renal replacement therapy (RRT) are at high risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through effects on platelets and coagulation cascades. No high-quality randomized clinical trials have previously assessed the benefits and harms of prophylactic proton pump inhibitor use in this high-risk population of adult critically ill patients...
January 10, 2018: Trials
https://www.readbyqxmd.com/read/29316555/intestinal-dysbiosis-secondary-to-proton-pump-inhibitor-use
#7
Yuji Naito, Kaori Kashiwagi, Tomohisa Takagi, Akira Andoh, Ryo Inoue
BACKGROUND: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use. SUMMARY: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease...
January 6, 2018: Digestion
https://www.readbyqxmd.com/read/29310122/dietary-trehalose-enhances-virulence-of-epidemic-clostridium-difficile
#8
J Collins, C Robinson, H Danhof, C W Knetsch, H C van Leeuwen, T D Lawley, J M Auchtung, R A Britton
Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection...
January 3, 2018: Nature
https://www.readbyqxmd.com/read/29309934/update-of-treatment-algorithms-for-clostridium-difficile-infection
#9
REVIEW
R E Ooijevaar, Y H van Beurden, E M Terveer, A Goorhuis, M P Bauer, J J Keller, C J J Mulder, E J Kuijper
BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhea, both in healthcare facilities and the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the ESCMID guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI. AIM: To review novel treatments and approaches for CDI, except probiotics and vaccines...
January 5, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29309845/non-conventional-antimicrobial-and-alternative-therapies-for-the-treatment-of-clostridium-difficile-infection
#10
REVIEW
Niloufar Roshan, Katherine A Hammer, Thomas V Riley
Clostridium difficile is an anaerobic, Gram-positive, spore-forming bacillus that causes disease ranging from self-limiting diarrhoea to severe pseudomembranous colitis. C. difficile infection (CDI) commonly affects hospitalised patients and is increasingly identified in patients in the community with no hospital contact. For the last 15 years the incidence of CDI worldwide has been rising, especially in the northern hemisphere. The yearly average number of hospitalizations as a result of this disease is estimated to be over a quarter of a million per year in the United States alone...
January 5, 2018: Anaerobe
https://www.readbyqxmd.com/read/29305541/assessing-the-burden-of-c-difficile-infection-in-low-and-middle-income-countries
#11
G A Roldan, A X Cui, N R Pollock
In contrast to the significant resources invested in diagnosis and prevention of C. difficile infection (CDI) in resource-rich settings, in resource-limited settings patients with community- and hospital-acquired diarrhea may not routinely be tested for CDI. Is CDI actually less frequent or severe in resource-limited settings, or might we be missing an important opportunity to prevent CDI-related morbidity and mortality (and to promote antibiotic stewardship) in these settings? Here, we review the literature to assess the overall burden of CDI in low- and middle-income countries...
January 5, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29305285/national-healthcare-safety-network-laboratory-identified-clostridium-difficile-event-reporting-a-need-for-diagnostic-stewardship
#12
Clare Rock, Zoi Pana, Surbhi Leekha, Polly Trexler, Jennifer Andonian, Avinash Gadala, Karen C Carroll, Lisa L Maragakis
We describe the proportion of health care facility-onset Clostridium difficile infection (HO-CDI) National Healthcare Safety Network laboratory-identified events at our facility that were deemed nontrue HO-CDIs. Reasons included testing in a patient without significant diarrhea or with recent laxative use, or delayed testing. Standardized infection ratios using only true HO-CDI in the numerator were improved compared with publically reported standardized infection ratios. A prioritization matrix identifies which clinical services could benefit most from directed diagnostic stewardship interventions...
January 2, 2018: American Journal of Infection Control
https://www.readbyqxmd.com/read/29305281/impact-of-real-time-notification-of-clostridium-difficile-test-results-and-early-initiation-of-effective-antimicrobial-therapy
#13
Christian B Polen, William R Judd, Patrick D Ratliff, Gregory S King
BACKGROUND: Clostridium difficile is a prominent nosocomial pathogen and is the most common causative organism of health care-associated diarrhea. To our knowledge, no studies have investigated the impact of real-time notification of culture results with rapid antimicrobial stewardship program (ASP) intervention in the setting of C difficile infection (CDI). The purpose of this study was to assess the impact of real-time notification of detection of toxigenic C difficile by DNA amplification results in patients with confirmed CDI...
January 3, 2018: American Journal of Infection Control
https://www.readbyqxmd.com/read/29300048/therapy-oral-capsule-fmt-effective-for-c-difficile-infection
#14
Iain Dickson
No abstract text is available yet for this article.
January 4, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29290480/cleaning-the-air-with-ultraviolet-germicidal-irradiation-lessened-contact-infections-in-a-long-term-acute-care-hospital
#15
Tina Ethington, Sherry Newsome, Jerri Waugh, Linda D Lee
BACKGROUND: This study was designed to determine whether removing bacteria from the air with ultraviolet germicidal irradiation (UV-C) at the room level would reduce infection rates. METHODS: We reviewed infection data for 12 months before and after UV-C installation in the special care unit (SCU) of a long-term acute care hospital. All patients admitted to the SCU during the study time frame were included. Microbiologic impactor air sampling was completed in August 2015...
December 29, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/29290473/effective-utilization-of-c-difficile-pcr-and-identification-of-clinicopathologic-factors-associated-with-conversion-to-a-positive-result-in-symptomatic-patients
#16
Mohamed E Mostafa, Timothy Flynn, Christopher P Hartley, Nathan A Ledeboer, Blake W Buchan
OBJECTIVES: We assess the diagnostic yield of repeat testing for C. difficile using molecular methods within 7days of a negative test and identify specific factors associated with conversion from negative to positive test result within a 7-day period to aid in selective test utilization. METHODS: A retrospective chart review of 20,866 laboratory test orders for C. difficile PCR was conducted. The test result, clinicopathologic patient features, and previous test results were recorded...
December 6, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29289484/what-do-we-know-about-the-diagnostics-treatment-and-epidemiology-of-clostridioides-clostridium-difficile-infection-in-europe
#17
REVIEW
Elisabeth Nagy
Clostridium difficile, recently reclassified as Clostridioides difficile is responsible for a significant part of diarrheal diseases in the hospitals and in the community. Besides the main pathogenic factors, toxin A, toxin B and the binary toxin, several other putative virulence factors have been investigated. This manuscript summarize recent findings in Europe concerning source of infection, epidemiology of CDI, the changing pattern of PCR ribotypes of C. difficile strains in different European countries, recommendations for diagnosis and treatment of CDI...
December 27, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29287077/ribotype-078-clostridium-difficile-infection-incidence-in-dutch-hospitals-is-not-associated-with-provincial-pig-farming-results-from-a-national-sentinel-surveillance-2009-2015
#18
Sofie M van Dorp, Sabine C de Greeff, Céline Harmanus, Ingrid M J G Sanders, Olaf M Dekkers, Cornelis W Knetsch, Greetje A Kampinga, Daan W Notermans, Ed J Kuijper
BACKGROUND: It has been suggested that the high incidence of ribotype 078 Clostridium difficile infections (CDI) in the Netherlands is related to pig farming. METHODS: We used data of hospitalised CDI patients (>2yrs of age) diagnosed between May 2009 and May 2015 in 26 hospitals participating in a national sentinel surveillance. We compared clinical and geographical characteristics of 078 CDI to other CDI. We investigated the association between 078 CDI incidence and four indicators of pig farming (piglet, pig, piglet farm and pig farm density) by mixed-effects Poisson regression...
2017: PloS One
https://www.readbyqxmd.com/read/29285574/clostridium-difficile-related-postinfectious-ibs-a-case-of-enteroglial-microbiological-stalking-and-or-the-solution-of-a-conundrum
#19
EDITORIAL
Gabrio Bassotti, Lara Macchioni, Lanfranco Corazzi, Pierfrancesco Marconi, Katia Fettucciari
Post-infectious irritable bowel syndrome is a well-defined pathological entity that develops in about one-third of subjects after an acute infection (bacterial, viral) or parasitic infestation. Only recently it has been documented that an high incidence of post-infectious irritable bowel syndrome occurs after Clostridium difficile infection. However, until now it is not known why in some patients recovered from this infection the gastrointestinal disturbances persist for months or years. Based on our in vitro studies on enteric glial cells exposed to the effects of C...
December 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29280808/improved-patient-hand-hygiene-reduces-c-difficile-infections-in-hospitals
#20
Karen Rosenberg
No abstract text is available yet for this article.
January 2018: American Journal of Nursing
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