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A von Braun, C Lübbert
The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence...
March 13, 2018: Der Internist
Isobel Ramsay, Nicholas M Brown, David A Enoch
Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab)...
2018: Infectious Diseases
Myreen E Tomas, Thriveen S C Mana, Brigid M Wilson, Michelle M Nerandzic, Joussef Samira, Miguel Quinones-Mateu, Curtis J Donskey
Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections. One rationale for tapering and pulsing of the dose at the end of therapy is to reduce the selective pressure of vancomycin on the indigenous intestinal microbiota. Here, we used a mouse model to test the hypothesis that the indigenous microbiota that provide colonization resistance against C. difficile and vancomycin-resistant enterococci (VRE) is re-populated during tapering courses of vancomycin. Mice were treated orally with vancomycin daily for 10 days, vancomycin in a tapering dose for 42 days, fidaxomicin for 10 days, or saline...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Cyrus Jahansouz, Christopher Staley, Scott Kizy, Hongliang Xu, Ann V Hertzel, Jessi Coryell, Stephanie Singroy, Matthew Hamilton, Meri DuRand, David A Bernlohr, Michael J Sadowsky, Alexander Khoruts, Sayeed Ikramuddin
OBJECTIVE: The aim of this study was to test whether the perioperative composition of intestinal microbiota can contribute to variable outcomes following vertical sleeve gastrectomy (VSG). SUMMARY OF BACKGROUND DATA: Although bariatric surgery is the most effective treatment for obesity, metabolic outcomes are variable. METHODS: Diet-induced obese mice were randomized to VSG or sham surgery, with or without exposure to antibiotics that selectively suppress mainly gram-positive (fidaxomicin, streptomycin) or gram-negative (ceftriaxone) bacteria on postoperative days (POD) 1-4...
March 8, 2018: Annals of Surgery
Adrián Martínez-Meléndez, Laura Tijerina-Rodríguez, Rayo Morfin-Otero, Adrián Camacho-Ortíz, Licet Villarreal-Treviño, Hugo Sánchez-Alanís, Eduardo Rodríguez-Noriega, Simon D Baines, Samantha Flores-Treviño, Héctor Jesús Maldonado-Garza, Elvira Garza-González
OBJECTIVE: To assess drug susceptibility and characterize Clostridium difficile ribotypes in isolates from two tertiary-care hospitals in Mexico. METHODS: Isolates were evaluated for genotyping, antimicrobial susceptibility testing and detection of mutations associated with drug resistance. PCR ribotyping was performed using a combination of gel-based and capillary electrophoresis-based approaches. RESULTS: MIC50 and MIC90 were ≥128 mg/L for ciprofloxacin, erythromycin, clindamycin, and rifampicin...
February 27, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Hande Boyaci, James Chen, Mirjana Lilic, Margaret Palka, Rachel Anne Mooney, Robert Landick, Seth A Darst, Elizabeth A Campbell
Fidaxomicin (Fdx) is an antimicrobial RNA polymerase (RNAP) inhibitor highly effective against Mycobacterium tuberculosis RNAP in vitro , but clinical use of Fdx is limited to treating Clostridium difficile intestinal infections due to poor absorption. To identify the structural determinants of Fdx binding to RNAP, we determined the 3.4 Å cryo-electron microscopy structure of a complete M. tuberculosis RNAP holoenzyme in complex with Fdx. We find that the actinobacteria general transcription factor RbpA contacts fidaxomycin, explaining its strong effect on M...
February 26, 2018: ELife
N J Ajami, J L Cope, M C Wong, J F Petrosino, L Chesnel
Clostridium difficile infection (CDI), a common cause of hospital-acquired infections, typically occurs after disruption of the normal gut microbiome by broad-spectrum antibiotics. Fidaxomicin is a narrow-spectrum antibiotic that demonstrates reduced impact on the normal gut microbiota and is approved for the treatment of CDI. To further explore the benefits of this property, we used a murine model to examine the effects of fidaxomicin versus vancomycin on gut microbiota and susceptibility to C. difficile colonization while tracking microbiota recovery over time...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Phuc Le, Van T Nghiem, Patricia Dolan Mullen, Abhishek Deshpande
BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication...
February 21, 2018: Infection Control and Hospital Epidemiology
James A Karlowsky, Heather J Adam, Tyler Kosowan, Melanie R Baxter, Kim A Nichol, Nancy M Laing, George Golding, George G Zhanel
Clostridium difficile toxin-positive diarrheal stool specimens submitted to eight Canadian hospital laboratories from 2013 to 2015 were cultured. Polymerase chain reaction ribotyping of isolates was performed using an internationally standardized, high-resolution capillary gel-based electrophoresis protocol and antimicrobial susceptibility testing conducted by CLSI-defined agar dilution (M11-A8, 2012). Among the 1310 isolates of C. difficile cultured, 141 different ribotypes were identified; the most common ribotypes were 027 (24...
January 31, 2018: Diagnostic Microbiology and Infectious Disease
Melina Miia Malinen, Izna Ali, Jacqueline Bezençon, James John Beaudoin, Kim L R Brouwer
The heteromeric steroid transporter, organic solute transporter alpha/beta (OSTα/β; SLC51), was discovered over a decade ago, but its physiological significance in the liver is still uncertain. A major challenge has been the lack of suitable models expressing OSTα/β. Based on observations first reported herein that hepatic OSTα/β is upregulated in nonalcoholic steatohepatitis (NASH), the aim of this research was to develop an in vitro model to evaluate OSTα/β function and interaction with drugs and bile acids...
February 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Fidelma Fitzpatrick, Mairead Skally, Melissa Brady, Karen Burns, Christopher Rooney, Mark H Wilcox
Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e...
2018: Advances in Experimental Medicine and Biology
Katsunori Yanagihara, Norihiko Akamatsu, Junichi Matsuda, Norihito Kaku, Kiyomitsu Katsumata, Kosuke Kosai
The narrow-spectrum macrocyclic antibiotic fidaxomicin is approved for treatment of Clostridium difficile infection in many countries and is currently under evaluation in Japan for this indication. This study was conducted to evaluate the effects of fidaxomicin and its major metabolite, OP-1118, on Clostridium spp. isolated in Nagasaki University Hospital, Japan. Isolates were cultured and antimicrobial susceptibility analyses performed according to the Clinical Laboratory Standards Institute methods. Ninety-eight isolates were obtained between 2012 and 2015, 50 of C...
January 17, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Regina Lamendella, Justin R Wright, Jada Hackman, Christopher McLimans, David R Toole, William Bernard Rubio, Rebecca Drucker, Hoi Tong Wong, Kate Sabey, John P Hegarty, David B Stewart
Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States, being associated with high recurrence and persistence rates. Though the relationship between intestinal dysbiosis and CDI is well known, it is unclear whether different forms of dysbiosis may potentially affect the course of CDI. How this is further influenced by C. difficile-directed antibiotics is virtually uninvestigated. In this study, diarrheal stool samples were collected from 20 hospitalized patients, half of whom were confirmed to have CDI...
January 2018: MSphere
S E Giancola, R J Williams, C A Gentry
WHAT IS KNOWN AND OBJECTIVE: Fidaxomicin was recently approved for the treatment of Clostridium difficile infection (CDI). Limited data on its use exist outside of the phase 3 trials. The purposes of this study were to assess the compliance with the Veterans Health Administration (VHA) fidaxomicin criteria for use and describe patient characteristics and outcomes following fidaxomicin treatment for CDI using real-world data within the VHA system. METHODS: This was a multicentre, retrospective, observational study including all adult patients who received at least 1 dose of fidaxomicin at any Veterans Affairs Medical Center...
January 21, 2018: Journal of Clinical Pharmacy and Therapeutics
T Galpérine, B Guery
Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus recognized as an evolving international health problem. Metronidazole and vancomycin were - until recently - the only drugs available to treat C. difficile infection (CDI). Better knowledge of the pathophysiology and the development of new drugs completely modified the management of initial episodes and recurrences of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin. New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole, rifaximin)...
January 11, 2018: Médecine et Maladies Infectieuses
S M Heimann, M R Cruz Aguilar, S Mellinghof, M J G T Vehreschild
Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential...
January 11, 2018: Médecine et Maladies Infectieuses
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 diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (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 6, 2018: Clinical Microbiology and Infection
Benoit Guery, Francesco Menichetti, Veli-Jukka Anttila, Nicholas Adomakoh, Jose Maria Aguado, Karen Bisnauthsing, Areti Georgopali, Simon D Goldenberg, Andreas Karas, Gbenga Kazeem, Chris Longshaw, Jose Alejandro Palacios-Fabrega, Oliver A Cornely, Maria J G T Vehreschild
BACKGROUND: Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin. METHODS: In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals...
December 19, 2017: Lancet Infectious Diseases
Adrián Camacho-Ortiz, Eva María Gutiérrez-Delgado, Jose F Garcia-Mazcorro, Soraya Mendoza-Olazarán, Adrián Martínez-Meléndez, Laura Palau-Davila, Simon D Baines, Héctor Maldonado-Garza, Elvira Garza-González
OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome. METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM...
2017: PloS One
Suzanne Arnott, Matthew Skancke, Sheena Chen, Bruce Abell
INTRODUCTION: Clostridium difficile is the most common cause of healthcare-associated infections and can have devastating morbidity and mortality. Traditional treatment algorithms involve intravenous metronidazole and enteric metronidazole or vancomycin. Fidaxomicin (DificidR ) targets "switch regions" within RNA polymerases and effectively kills clostridium difficile bacteria and is typically administered orally primarily or through a naso/oro-gastric conduit. PRESENTATION OF CASE: 55-year-old with a recent elective surgical procedure was hospitalized with multifocal pneumonia and subsequently developed clostridium difficile colitis...
2018: International Journal of Surgery Case Reports
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