Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate Clostridium difficile colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available by mouth, as a cream or gel, and by injection into a vein.
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.
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.
Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.
Ramoplanin (INN) is a glycolipodepsipeptide antibiotic drug derived from strain ATCC 33076 of Actinoplanes. It is effective against Gram-positive bacteria.
Ceftaroline fosamil (INN), brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. It retains some activity of later-generation cephalosporins having broad-spectrum activity against Gram-negative bacteria, but its effectiveness is relatively much weaker. It is currently being investigated for community-acquired pneumonia and complicated skin and skin structure infection.
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.
Lipoglycopeptides are a class of antibiotic that have lipophilic side-chains linked to glycopeptides. The class includes oritavancin, telavancin and dalbavancin.
Bezlotoxumab, sold under the brand name Zinplava, is a human monoclonal antibody designed for the prevention of recurrence of Clostridioides difficile infections.
Rifalazil is an antibiotic substance that kills bacterial cells by blocking off the β-subunit in RNA polymerase. Rifalazil is used as treatments for many different diseases. Of the most common are Chlamydia infection, Clostridium difficile associated diarrhea (CDAD), and tuberculosis (TB). Using rifalazil and the effects that coincide with taking rifalazil for treating a bacterial disease vary from person to person, as does any drug put into the human body. Food interactions and genetic variation are a few causes for the variation in side effects from the use of rifalazil. Its development was terminated in 2013 due to severe side effects.
Cadazolid is an experimental antibiotic of the oxazolidinone class made by Actelion Pharmaceuticals Ltd. which is effective against Clostridium difficile, a major cause of drug resistant diarrhea in the elderly. Current drug treatments for this infection involve orally delivered antibiotics, principally fidaxomicin, metronidazole and vancomycin; the last two drugs are the principal therapeutic agents in use, but fail in approximately 20 to 45% of the cases. The drug works by inhibiting synthesis of proteins in the bacteria, thus inhibiting the production of toxins and the formation of spores. Cadazolid progressed through to Phase III clinical trials, but in its financial results for Q1 2018, Idorsia mentions that Actelion informed them that "following completion of Phase 3 data analysis of cadazolid - it has decided to discontinue the development of the compound."
Nemonoxacin is a non-fluorinated quinolone antibiotic undergoing clinical trials. It has the same mechanism of action as fluouroquinolones; it inhibits DNA gyrase, preventing DNA synthesis, gene duplication, and cell division. At the end of 2016, it had reached market in Taiwan, Russia, the Commonwealth Independent States, Turkey, mainland China, and Latin America under the brand name Taigexyn. Nemonoxacin has completed phase 2 trials in the US and has moved on to phase 3 trials. The U.S. Food and Drug Administration (FDA) has granted nemonoxacin qualified infectious disease product (QIDP) and fast track designations for community-acquired bacterial pneumonia (CAP) and acute bacterial skin and skin-structure infections (ABSSSI).
Surotomycin was an investigational oral antibiotic. This macrolide antibiotic was under investigation by Merck & Co for the treatment of life-threatening Diarrhea, commonly caused by the bacterium Clostridium difficile. After reaching phase III in clinical trials, its production was discontinued in 2017 due to its non-superiority to current therapies.
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 that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as C. difficile, or C. diff, is 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 (CDT). Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.
Martha Rebecca Jane Clokie is a Professor of Microbiology at the University of Leicester. Her research investigates the identification and development of bacteriophages that kill pathogens in an effort to develop new antimicrobials.
Fecal microbiota, sold under the brand name, Rebyota is used for the prevention of recurrence of Clostridioides difficile infection.
