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Clostridioides difficile infection , also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea. Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.
The Clostridia are a highly polyphyletic class of Bacillota, including Clostridium and other similar genera. They are distinguished from the Bacilli by lacking aerobic respiration. They are obligate anaerobes and oxygen is toxic to them. Species of the class Clostridia are often but not always Gram-positive and have the ability to form spores. Studies show they are not a monophyletic group, and their relationships are not entirely certain. Currently, most are placed in a single order called Clostridiales, but this is not a natural group and is likely to be redefined in the future.
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine is present to prevent drug abuse and overdose. It should not be given to children due to the risk that they will stop breathing and should not be used in people with Clostridium difficile infection.
Ferring Pharmaceuticals is a Swiss multinational biopharmaceutical company specialising in areas such as reproductive health, maternal health, gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 years.
Fecal microbiota transplant (FMT), also known as a stool transplant, is the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT is an effective treatment for Clostridioides difficile infection (CDI). For recurrent CDI, FMT is more effective than vancomycin alone, and may improve the outcome after the first index infection.
Rifaximin, is a non-absorbable, broad spectrum antibiotic mainly used to treat travelers' diarrhea. It is based on the rifamycin antibiotics family. Since its approval in Italy in 1987, it has been licensed in over more than 30 countries for the treatment of a variety of gastrointestinal diseases like irritable bowel syndrome, and hepatic encephalopathy. It acts by inhibiting RNA synthesis in susceptible bacteria by binding to the RNA polymerase enzyme. This binding blocks translocation, which stops transcription. It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.
Cefdinir, sold under the brand name Omnicef among others, is an antibiotic used to treat pneumonia, otitis media, strep throat, and cellulitis. It is a less preferred option for pneumonia, otitis media, and strep throat which may be used in those with a severe allergy to penicillin. It is taken by mouth.
Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotics. Microbiotal alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as Clostridium difficile. It is defined as frequent loose and watery stools with no other complications.
Lubiprostone, sold under the brand name Amitiza among others, is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. The drug is owned by Mallinckrodt and is marketed by Takeda Pharmaceutical Company.
Fidaxomicin, sold under the brand name Dificid among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. Fidaxomicin is minimally absorbed into the bloodstream when taken orally, is bactericidal, and selectively eradicates pathogenic Clostridioides difficile with relatively little disruption to the multiple species of bacteria that make up the normal, healthy intestinal microbiota. The maintenance of normal physiological conditions in the colon may reduce the probability of recurrence of Clostridioides difficile infection.
Bezlotoxumab, sold under the brand name Zinplava, is a human monoclonal antibody designed for the prevention of recurrence of Clostridioides difficile infections.
Crofelemer is an antidiarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Other possible uses include diarrhea in children, acute infectious diarrhea, and diarrhea in patients with irritable bowel syndrome. It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.
Bacteriotherapy is the purposeful use of bacteria or their products in treating an illness. Forms of bacteriotherapy include the use of probiotics, microorganisms that provide health benefits when consumed; fecal matter transplants (FMT) /intestinal microbiota transplant (IMT), the transfer of gut microorganisms from the fecal matter of healthy donors to recipient patients to restore microbiota; or synbiotics which combine prebiotics, indigestible ingredients that promote growth of beneficial microorganisms, and probiotics. Through these methods, the gut microbiota, the community of 300-500 microorganism species that live in the digestive tract of animals aiding in digestion, energy storage, immune function and protection against pathogens, can be recolonized with favorable bacteria, which in turn has therapeutic effects.
Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
Ridinilazole is an investigational small molecule antibiotic being evaluated for oral administration to treat Clostridioides difficile infection (CDI). In vitro, it is bactericidal against C. difficile and suppresses bacterial toxin production; the mechanism of action is thought to involve inhibition of cell division. It has properties which are desirable for the treatment of CDI, namely that it is a narrow-spectrum antibiotic which exhibits activity against C. difficile while having little impact on other normal intestinal flora and that it is only minimally absorbed systemically after oral administration. At the time ridinilazole was developed, there were only three antibiotics in use for treating CDI: vancomycin, fidaxomicin, and metronidazole. The recurrence rate of CDI is high, which has spurred research into other treatment options with the aim to reduce the rate of recurrence.
Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.
Checkpoint inhibitor induced colitis is an inflammatory condition affecting the colon (colitis), which is caused by cancer immunotherapy. Symptoms typically consist of diarrhea, abdominal pain and rectal bleeding. Less commonly, nausea and vomiting may occur, which may suggest the present of gastroenteritis. The severity of diarrhea and colitis are graded based on the frequency of bowel movements and symptoms of colitis, respectively.
Nirogacestat, sold under the brand name Ogsiveo, is an anti-cancer medication used for the treatment of desmoid tumors. It is a selective gamma secretase inhibitor that is taken by mouth.
Live fecal microbiota spores, sold under the brand name Vowst, is a fecal microbiota product used to prevent the recurrence of Clostridioides difficile infection.
References
- 1 2 3 "Rebyota- donor human stool suspension". DailyMed. 13 January 2023. Archived from the original on 21 January 2023. Retrieved 21 January 2023.
- ↑ "Highlighting prescribing information". fda.gov. Archived from the original on 15 March 2023. Retrieved 4 April 2023.
- ↑ "Rebyota". U.S. Food and Drug Administration (FDA). 30 November 2022. Archived from the original on 4 December 2022. Retrieved 4 December 2022.
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "FDA Approves First Fecal Microbiota Product". U.S. Food and Drug Administration (FDA). 30 November 2022. Archived from the original on 30 November 2022. Retrieved 1 December 2022.
This article incorporates text from this source, which is in the public domain . - ↑ "Ferring Receives U.S. FDA Approval for Rebyota (fecal microbiota, live-jslm) – A Novel First-in-Class Microbiota-Based Live Biotherapeutic". Ferring Pharmaceuticals USA. 1 December 2022. Archived from the original on 1 December 2022. Retrieved 1 December 2022.
