Metronidazole

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Metronidazole
Metronidazole.svg
Metronidazole 3D 1w3r.png
Clinical data
AHFS/Drugs.com Monograph
MedlinePlus a689011
License data
Pregnancy
category
Routes of
administration 		By mouth, topical, rectal, intravenous, vaginal
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 80% (by mouth), 60–80% (rectal), 20–25% (vaginal) [6] [7] [8]
Protein binding 20% [6] [7]
Metabolism Liver [6] [7]
Metabolites Hydroxymetronidazole
Elimination half-life 8 hours [6] [7]
Excretion Urine (77%), faeces (14%) [6] [7]
Identifiers
  • 2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethanol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.006.489 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C6H9N3O3
Molar mass 171.156 g·mol−1
3D model (JSmol)
Melting point 159 to 163 °C (318 to 325 °F)
  • OCCn1c(C)ncc1[N+](=O)[O-]
  • InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3 Yes check.svgY
  • Key:VAOCPAMSLUNLGC-UHFFFAOYSA-N Yes check.svgY
   (verify)

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. [9] It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. [9] It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. [9] It is an option for a first episode of mild-to-moderate Clostridioides difficile colitis if vancomycin or fidaxomicin is unavailable. [9] [10] Metronidazole is available orally (by mouth), as a cream or gel, and by slow intravenous infusion (injection into a vein). [9] [3]

Contents

Common side effects include nausea, a metallic taste, loss of appetite, and headaches. [9] Occasionally seizures or allergies to the medication may occur. [9] Some state that metronidazole should not be used in early pregnancy, while others state doses for trichomoniasis are safe. [1] [ weasel words ] Metronidazole is generally considered compatible with breastfeeding. [1] [11]

Metronidazole began to be commercially used in 1960 in France. [12] It is on the World Health Organization's List of Essential Medicines. [13] It is available in most areas of the world. [14] In 2020, it was the 222nd most commonly prescribed medication in the United States, with more than 2 million prescriptions. [15] [16]

Medical uses

A tube of metronidazole cream Metronidazole Aurobindo tube.jpg
A tube of metronidazole cream

Metronidazole has activity against some protozoans and most anaerobic bacteria (both Gram-negative and Gram-positive classes) but not the aerobic bacteria. [17] [18]

Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontal disease, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus , and Prevotella species. [19] It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery. [19]

Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This may require hydrolysis in the gastrointestinal tract and some sources speculate that it may be unsuitable in people with diarrhea or feeding-tubes in the duodenum or jejunum. [20] [21]

Bacterial vaginosis

Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. [22]

An effective treatment option for mixed infectious vaginitis is a combination of clotrimazole and metronidazole. [23]

Trichomoniasis

The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection with Trichomonas vaginalis . Treatment for both the infected patient and the patient's sexual partner is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option, but cure rates are much lower. [24]

Giardiasis

Oral metronidazole is a treatment option for giardiasis, however, the increasing incidence of nitroimidazole resistance is leading to the increased use of other compound classes. [25]

Dracunculus

In the case of Dracunculus medinensis (Guinea worm), metronidazole just eases worm extraction rather than killing the worm. [9]

C. difficile colitis

Initial antibiotic therapy for less-severe Clostridioides difficile infection colitis (pseudomembranous colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth. [10] In 2017, the IDSA generally recommended vancomycin and fidaxomicin over metronidazole. [10] Vancomycin by mouth has been shown to be more effective in treating people with severe C. difficile colitis. [26]

E. histolytica

Entamoeba histolytica invasive amebiasis is treated with metronidazole for eradication, in combination with diloxanide to prevent recurrence. [27] Although it is generally a standard treatment it is associated with some side effects. [28]

Preterm births

Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). Metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole. [29]

Hypoxic radiosensitizer

In addition to its anti-biotic properties, attempts were also made to use a possible radiation-sensitizing effect of metronidazole in the context of radiation therapy against hypoxic tumors. [30] However, the neurotoxic side effects occurring at the required dosages have prevented the widespread use of metronidazole as an adjuvant agent in radiation therapy. [31] However, other nitroimidazoles derived from metronidazole such as nimorazole with reduced electron affinity showed less serious neuronal side effects and have found their way into radio-onological practice for head and neck tumors in some countries. [32]

Perioral dermatitis

Canadian Family Physician has recommended topical metronidazole as a third-line treatment for the perioral dermatitis either along with or without oral tetracycline or oral erythromycin as first and second line treatment respectively. [33]

Adverse effects

Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhea, weight loss, abdominal pain, vomiting, headache, dizziness, and metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia. [19] High doses and long-term systemic treatment with metronidazole are associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity. [19] Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes). [19] [34] Metronidazole has been associated with cancer in animal studies. [35] [ failed verification ] In rare cases, it can also cause temporary hearing loss that reverses after cessation of the treatment. [36] [37]

Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date. [38] [39]

Mutagenesis and carcinogenesis

In 2016 metronidazole was listed by the U.S. National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen. [40] Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures. [40] [41] The relationship between exposure to metronidazole and human cancer is unclear. [40] [42] One study [43] found an excess in lung cancer among women (even after adjusting for smoking), while other studies [44] [45] [46] found either no increased risk, or a statistically insignificant risk. [40] [47] Metronidazole is listed as a possible carcinogen according to the World Health Organization (WHO) International Agency for Research on Cancer (IARC). [48] A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole. [41]

Stevens–Johnson syndrome

Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high rates when combined with mebendazole. [49]

Drug interactions

Alcohol

Consuming alcohol while taking metronidazole has been suspected in case reports to cause a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia, and shortness of breath. [50] People are often advised not to drink alcohol during systemic metronidazole therapy and for at least 48 hours after completion of treatment. [19] However, some studies call into question the mechanism of the interaction of alcohol and metronidazole, [51] [52] [53] and a possible central toxic serotonin reaction for the alcohol intolerance is suggested. [38] Metronidazole is also generally thought to inhibit the liver metabolism of propylene glycol (found in some foods, medicines, and in many electronic cigarette e-liquids), thus propylene glycol may potentially have similar interaction effects with metronidazole.[ medical citation needed ]

Other drug interactions

Metronidazole is a moderate CYP2C9 inhibitor. CYP2C9 is an enzyme of cytochrome P450 family. Therefore, metronidazole may interact with medications metabolized by this enzyme. [54] [55] [56] Examples of such medications are lomitapide, warfarin, etc. [6]

Pharmacology

Mechanism of action

Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by forming nitroso radicals, which disrupt the DNA of microbial cells. [6] [57] This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic bacteria and protozoans, it has relatively little effect upon human cells or aerobic bacteria. [58]

Pharmacokinetics

Hydroxymetronidazole, the main metabolite Hydroxymetronidazole.svg
Hydroxymetronidazole, the main metabolite

Oral metronidazole is approximately 80% bioavailable via the gut and peak blood plasma concentrations occur after one to two hours. Food may slow down absorption but does not diminish it. Of the circulating substance, about 20% is bound to plasma proteins. It penetrates well into tissues, the cerebrospinal fluid, the amniotic fluid and breast milk, as well as into abscess cavities. [57]

About 60% of the metronidazole is metabolized by oxidation to the main metabolite hydroxymetronidazole and a carboxylic acid derivative, and by glucuronidation. The metabolites show antibiotic and antiprotozoal activity in vitro . [57] Metronidazole and its metabolites are mainly excreted via the kidneys (77%) and to a lesser extent via the faeces (14%). [6] [7] The biological half-life of metronidazole in healthy adults is eight hours, in infants during the first two months of their lives about 23 hours, and in premature babies up to 100 hours. [57]

The biological activity of hydroxymetronidazole is 30% to 65%, and the elimination half-life is longer than that of the parent compound. [59] The serum half-life of hydroxymetronidazole after suppository was 10 hours, 19 hours after intravenous infusion, and 11 hours after a tablet. [60]

Bacterial resistance

Bacteria may have developed unexpectedly higher resistance to metronidazole. [61] [62] [63] [ clarification needed ]

History

The drug was initially developed by Rhône-Poulenc in the 1950s [64] and licensed to G.D. Searle. [65] Searle was acquired by Pfizer in 2003. [66] The original patent expired in 1982, but evergreening reformulation occurred thereafter. [67]

Brand name

In India, it is sold under the brand name Metrogyl and Flagyl. [68] In Bangladesh, it is available as Amodis, Amotrex, Dirozyl, Filmet, Flagyl, Flamyd, Metra, Metrodol, Metryl, etc. [69] In Pakistan, it is sold under the brand name of Flagyl and Metrozine.[ citation needed ] In the United States it is sold under the brand name Noritate. [70]

Synthesis

2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3): [71] [72] [73]

Synthesis of metronidazole.png

Research

Metronidazole is researched for its anti-inflammatory and immunomodulatory properties. Studies have shown that metronidazole can decrease the production of reactive oxygen species (ROS) and nitric oxide by activated immune cells, such as macrophages and neutrophils. Metronidazole's immunomodulatory properties are thought to be related to its ability to decrease the activation of nuclear factor-kappa B (NF-κB), a transcription factor that regulates the expression of pro-inflammatory cytokines, including chemokines, and adhesion molecules. Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response. [74] Chemokines are a type of cytokines that act as chemoattractants, meaning they attract and guide immune cells to specific sites in the body where they are needed. [75] Cell adhesion molecules play an important role in the immune response by facilitating the interaction between immune cells and other cells in the body, such as endothelial cells, which form the lining of blood vessels. [76] By inhibiting NF-κB activation, metronidazole can reduce the production of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-1β. [77] Metronidazole has been studied in various immunological disorders, including inflammatory bowel disease, periodontitis, and rosacea. In these conditions, metronidazole has been suspected to have anti-inflammatory and immunomodulatory effects that could be beneficial in the treatment of these conditions. [78] Despite the success in treating rosacea with metronidazole, [79] [80] [81] [82] [83] the exact mechanism of why metronidazole in rosacea is efficient is not precisely known, i.e., which properties of metronidazole help treat rosacea: antibacterial or immunomodulatory or both, or other mechanism is involved. [84] [85] Increased ROS production in rosacea is thought to contribute to the inflammatory process and skin damage, so metronidazole's ability to decrease ROS may explain the mechanism of action in this disease, but this remains speculation. [86] [87]

Veterinary use

Metronidazole is used to treat infections of Giardia in dogs, cats, and other companion animals, but it does not reliably clear infection with this organism and is being supplanted by fenbendazole for this purpose in dogs and cats. [88] It is also used for the management of chronic inflammatory bowel disease in cats and dogs. [89] Another common usage is the treatment of systemic and/or gastrointestinal clostridial infections in horses. Metronidazole is used in the aquarium hobby to treat ornamental fish and as a broad-spectrum treatment for bacterial and protozoan infections in reptiles and amphibians. In general, the veterinary community may use metronidazole for any potentially susceptible anaerobic infection. The U.S. Food and Drug Administration (FDA) suggests it only be used when necessary because it has been shown to be carcinogenic in mice and rats, as well as to prevent antimicrobial resistance. [90] [91]

Related Research Articles

<span class="mw-page-title-main">Bacterial vaginosis</span> Excessive growth of bacteria in the vagina

Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.

<span class="mw-page-title-main">Trichomoniasis</span> Medical condition

Trichomoniasis (trich) is an infectious disease caused by the parasite Trichomonas vaginalis. About 70% of affected people do not have symptoms when infected. When symptoms occur, they typically begin 5 to 28 days after exposure. Symptoms can include itching in the genital area, a bad smelling thin vaginal discharge, burning with urination, and pain with sex. Having trichomoniasis increases the risk of getting HIV/AIDS. It may also cause complications during pregnancy.

<span class="mw-page-title-main">Vancomycin</span> Antibiotic medication

Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is used intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally as a treatment for severe Clostridium difficile colitis. When taken orally it is poorly absorbed.

Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.

<i>Clostridioides difficile</i> infection Disease caused by C. difficile bacteria

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.

<span class="mw-page-title-main">Azathioprine</span> Immunosuppressive medication

Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus; and in kidney transplants to prevent rejection. It is listed by the International Agency for Research on Cancer as a group 1 human carcinogen. It is taken by mouth or injected into a vein.

<span class="mw-page-title-main">Clindamycin</span> Antibiotic

Clindamycin is a lincosamide antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media, and endocarditis. It can also be used to treat acne, and some cases of methicillin-resistant Staphylococcus aureus (MRSA). In combination with quinine, it can be used to treat malaria. It is available by mouth, by injection into a vein, and as a cream or a gel to be applied to the skin or in the vagina.

<span class="mw-page-title-main">Doxycycline</span> Tetracycline-class antibiotic

Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis. It is also used to prevent malaria. Doxycycline may be taken by mouth or by injection into a vein.

<span class="mw-page-title-main">Rosacea</span> Skin condition resulting in redness, pimples and swelling, usually on the face

Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarged nose may occur in severe disease, a condition known as rhinophyma.

<span class="mw-page-title-main">Rifaximin</span> Antibiotic medication

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.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

Management of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Since Crohn's disease is an immune system condition, it cannot be cured by medication or surgery. Treatment initially involves the use of medications to eliminate infections and reduce inflammation. Surgery may be required for complications such as obstructions, fistulae, abscesses, or if the disease does not respond to drugs within a reasonable time. However, surgery cannot cure Crohn's disease. It involves removing the diseased part of the intestine and rejoining the healthy ends, but the disease tends to recur after surgery.

Dysbiosis is characterized by a disruption to the microbiome resulting in an imbalance in the microbiota, changes in their functional composition and metabolic activities, or a shift in their local distribution. For example, a part of the human microbiota such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract.

<span class="mw-page-title-main">Benznidazole</span> Chemical compound

Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its moderate side effects compared to nifurtimox. It is taken by mouth.

Helicobacter pylori eradication protocols is a standard name for all treatment protocols for peptic ulcers and gastritis in the presence of Helicobacter pylori infection. The primary goal of the treatment is not only temporary relief of symptoms but also total elimination of H. pylori infection. Patients with active duodenal or gastric ulcers and those with a prior ulcer history should be tested for H. pylori. Appropriate therapy should be given for eradication. Patients with MALT lymphoma should also be tested and treated for H. pylori since eradication of this infection can induce remission in many patients when the tumor is limited to the stomach. Several consensus conferences, including the Maastricht Consensus Report, recommend testing and treating several other groups of patients but there is limited evidence of benefit. This includes patients diagnosed with gastric adenocarcinoma, patients found to have atrophic gastritis or intestinal metaplasia, as well as first-degree relatives of patients with gastric adenocarcinoma since the relatives themselves are at increased risk of gastric cancer partly due to the intrafamilial transmission of H. pylori. To date, it remains controversial whether to test and treat all patients with functional dyspepsia, gastroesophageal reflux disease, or other non-GI disorders as well as asymptomatic individuals.

<span class="mw-page-title-main">Polypeptide antibiotic</span> Class of antibiotics

Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin, bacitracin, colistin, and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.

<span class="mw-page-title-main">Secnidazole</span> Chemical compound

Secnidazole is a nitroimidazole anti-infective. Effectiveness in the treatment of dientamoebiasis has been reported. It has also been tested against Atopobium vaginae.

<span class="mw-page-title-main">Fidaxomicin</span> Antibiotic

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.

<i>Clostridioides difficile</i> Species of bacteria

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.

<span class="mw-page-title-main">Ridinilazole</span> Chemical compound

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.

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