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https://www.readbyqxmd.com/read/29781761/prevention-and-treatment-of-clostridium-difficile-associated-diarrhea-by-reconstitution-of-the-microbiota
#1
Noa Eliakim-Raz, Jihad Bishara
This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state...
May 21, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29760164/%C3%A2-bezlotoxumab-for-prevention-of-recurrence-of-clostridium-difficile-infection
#2
(no author information available yet)
Clostridium difficile infection is a significant cause of infectious diarrhoea and is associated with considerable morbidity and mortality.1,2 Management of Clostridium difficile infection often requires treatment with antibiotics (metronidazole, vancomycin or fidaxomicin) alongside supportive care to manage hydration, electrolytes and nutrition. However, the risk of recurrence is approximately 20%.2 Here, we review the evidence for bezlotoxumab (▼ Zinplava - Merck Sharp & Dohme Limited), a monoclonal antibody licensed for the prevention of recurrence of Clostridium difficile in adults who are at high risk of recurrence...
May 2018: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/29746874/real-world-use-of-fidaxomicin-in-a-large-uk-tertiary-hospital-how-effective-is-it-for-treating-recurrent-disease
#3
D A Enoch, R Santos, C J Phillips, C Micallef, M Murphy, S H Aliyu, D Massey, N M Brown
We reviewed all courses of fidaxomicin use in our hospital. It was used for first recurrence (6 times), second recurrence (8) and third recurrence (once). One received fidaxomicin first-line. Eight patients initially responded to therapy. Three of these were asymptomatic at 90 days; three remained asymptomatic at 30 days and two had recurrences 5 and 9 days after stopping therapy. Four patients failed to respond; two required faecal transplantation and one required a colectomy. Two patients deteriorated and two patients died...
May 7, 2018: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29676573/tiacumicin-congeners-with-improved-antibacterial-activity-from-a-halogenase-inactivated-mutant
#4
Haibo Zhang, Xiaoxing Tian, Xiaohui Pu, Qingbo Zhang, Wenjun Zhang, Changsheng Zhang
Tiacumicin B (1, also known as fidaxomicin or difimicin) is a marketed drug for the treatment of Clostridium difficile infections. The biosynthetic pathway of 1 has been studied in Dactylosporangium aurantiacum subsp. hamdenensis NRRL 18085 and has enabled the identification of TiaM as a tailoring dihalogenase. Herein we report the isolation, structure elucidation, and bioactivity evaluation of 14 tiacumicin congeners (including 11 new ones) from the tiaM-inactivated mutant. A new tiacumicin congener, 3, with a propyl group at C-7‴ of the aromatic ring was found to exhibit improved antibacterial activity...
April 20, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29651860/risk-factors-for-clostridium-difficile-infections-in-baranya-county-southern-hungary
#5
Szabolcs Vigvári, Dávid Sipos, Ágnes Kappéter, Zsófia Feiszt, Beáta Kovács, Zoltán Péterfi
In the past decade, Clostridium difficile infections (CDIs) have become a major public health challenge. Their epidemiology has radically changed with a significant rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments are very common. Furthermore, a spread of CDI has emerged in general population without the usual risk factors (unexposed to antibiotic treatment, young people, etc.). The conventional treatments (metronidazole and vancomycin) are still effective and are the first-line antibiotics with new recommendations...
April 13, 2018: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29626003/probable-fidaxomicin-induced-pancytopenia
#6
Samantha Axtell, Aisha Shokoya, Christine Yocum
PURPOSE: A case of pancytopenia in a patient receiving treatment with fidaxomicin for Clostridium difficile infection (CDI) is described. SUMMARY: A 33-year-old Caucasian woman was admitted to the hospital with a chief complaint of loose stools occurring approximately 7 times a day; she also reported fever, nausea, diffuse abdominal pain, and fatigue. The patient had a history of recurrent CDI, recurrent urinary tract infections, nephrolithiasis, chronic hepatitis C, and endometriosis...
April 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29606590/structural-basis-of-transcription-inhibition-by-fidaxomicin-lipiarmycin-a3
#7
Wei Lin, Kalyan Das, David Degen, Abhishek Mazumder, Diego Duchi, Dongye Wang, Yon W Ebright, Richard Y Ebright, Elena Sineva, Matthew Gigliotti, Aashish Srivastava, Sukhendu Mandal, Yi Jiang, Yu Liu, Ruiheng Yin, Zhening Zhang, Edward T Eng, Dennis Thomas, Stefano Donadio, Haibo Zhang, Changsheng Zhang, Achillefs N Kapanidis, Richard H Ebright
Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm at 3.5-Å resolution. The structure shows that Lpm binds at the base of the RNAP "clamp." The structure exhibits an open conformation of the RNAP clamp, suggesting that Lpm traps an open-clamp state...
March 28, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29590752/total-synthesis-of-tiacumicin-a-total-synthesis-relay-synthesis-and-degradation-studies-of-fidaxomicin-tiacumicin-b-lipiarmycin-a3
#8
Hiromu Hattori, Elias Kaufmann, Hideki Miyatake-Ondozabal, Regina Berg, Karl Gademann
The commercial macrolide antibiotic fidaxomicin was synthesized in a highly convergent manner. Salient features of this synthesis include a β-selective noviosylation, a β-selective rhamnosylation, a ring closing metathesis, a Suzuki coupling and a vinylogous Mukaiyama aldol reaction. Careful choice of protecting groups and fine tuning of the glycosylation reactions led to the first total synthesis of fidaxomicin. In addition, a relay synthesis of fidaxomicin was established, which gives access to a conveniently protected intermediate from the natural material for derivatization...
March 29, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29536125/-treatment-of-acute-and-recurrent-clostridium-difficile-infections-what-is-new
#9
REVIEW
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...
May 2018: Der Internist
https://www.readbyqxmd.com/read/29535530/recent-progress-for-the-effective-prevention-and-treatment-of-recurrent-clostridium-difficile-infection
#10
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
https://www.readbyqxmd.com/read/29530853/tapering-courses-of-oral-vancomycin-induce-persistent-disruption-of-the-microbiota-that-provide-colonization-resistance-to-clostridium-difficile-and-vancomycin-resistant-enterococci-in-mice
#11
Myreen E Tomas, Thriveen S C Mana, Brigid M Wilson, Michelle M Nerandzic, Samira Joussef-Piña, Miguel E Quiñones-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 repopulated 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...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29521742/antibiotic-induced-disruption-of-intestinal-microbiota-contributes-to-failure-of-vertical-sleeve-gastrectomy
#12
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
https://www.readbyqxmd.com/read/29485939/circulation-of-highly-drug-resistant-clostridium-difficile-ribotypes-027-and-001-in-two-tertiary-care-hospitals-in-mexico
#13
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...
May 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29480804/fidaxomicin-jams-mycobacterium-tuberculosis-rna-polymerase-motions-needed-for-initiation-via-rbpa-contacts
#14
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
https://www.readbyqxmd.com/read/29463537/impact-of-oral-fidaxomicin-administration-on-the-intestinal-microbiota-and-susceptibility-to-clostridium-difficile-colonization-in-mice
#15
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 a 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...
May 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29463339/cost-effectiveness-of-competing-treatment-strategies-for-clostridium-difficile-infection-a-systematic-review
#16
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...
April 2018: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/29456070/pcr-ribotyping-and-antimicrobial-susceptibility-testing-of-isolates-of-clostridium-difficile-cultured-from-toxin-positive-diarrheal-stools-of-patients-receiving-medical-care-in-canadian-hospitals-the-canadian-clostridium-difficile-surveillance-study-can-diff
#17
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
https://www.readbyqxmd.com/read/29420067/organic-solute-transporter-ost%C3%AE-%C3%A3-is-over-expressed-in-nonalcoholic-steatohepatitis-and-modulated-by-drugs-associated-with-liver-injury
#18
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
https://www.readbyqxmd.com/read/29383667/european-practice-for-cdi-treatment
#19
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
https://www.readbyqxmd.com/read/29373265/susceptibility-of-clostridium-species-isolated-in-japan-to-fidaxomicin-and-its-major-metabolite-op-1118
#20
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
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