{"id":173,"date":"2023-06-25T10:00:20","date_gmt":"2023-06-25T09:00:20","guid":{"rendered":"https:\/\/microregistrar.com\/?p=173"},"modified":"2023-06-25T10:00:21","modified_gmt":"2023-06-25T09:00:21","slug":"metronidazole","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=173","title":{"rendered":"Metronidazole"},"content":{"rendered":"\n<p>Class:&nbsp;Nitroimidazole.<br>Mol weight:&nbsp;171<br>First used in 1960.<\/p>\n\n\n\n<figure class=\"wp-block-image\"><img decoding=\"async\" src=\"https:\/\/microregistrar.com\/wp-content\/uploads\/2021\/07\/image-6.png\" alt=\"02N \n\u0441\u043d\u0437 \nN \n\u043e\u043d \" class=\"wp-image-6471\"\/><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Mechanism of action<\/strong>:<\/h3>\n\n\n\n<p>Metronidazole enters the susceptible (bacterial\/parasite) cells by passive diffusion. It gets&nbsp;<strong>activated to a nitroso compound<\/strong>&nbsp;which causes&nbsp;<strong>oxidative damage to the DNA<\/strong>. It also<strong>&nbsp;inhibits DNA repair<\/strong>.<\/p>\n\n\n\n<p>The conversion of metronidazole to nitroso compound creates a concentration gradient, and more metronidazole enters the cells.<\/p>\n\n\n\n<p>The aerobic bacteria lack the necessary mechanism (lack sufficient redox potential) to activate this process and are resistant.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Mechanism of resistance:<\/strong><\/h3>\n\n\n\n<p>Metronidazole resistance is mostly studied in Bacteroides and H pylori.&nbsp;<\/p>\n\n\n\n<p><strong>In Bacteroides and some other anaerobes<\/strong>&nbsp;\u2013<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>5-nitroimidazole reductases, which reduce metronidazole to amine derivative instead of toxic nitroso compound. The&nbsp;<em>nim<\/em>&nbsp;gene encodes this enzyme. The&nbsp;<em>nim<\/em>&nbsp;has 9 variants and can exist on the chromosome, plasmid or transposon; the&nbsp;<em>nim<\/em>&nbsp;gene needs an upstream insertion sequence to exert its effect.<\/li>\n\n\n\n<li>Upregulation of multidrug efflux pump.<\/li>\n\n\n\n<li>Increase in lactate dehydrogenase activity to compensate for the decrease in pyruvate\/ferredoxin oxidoreductase (PFOR) activity.<\/li>\n\n\n\n<li>Upregulated rhamnose catabolism preventing metronidazole activation.<\/li>\n\n\n\n<li>Overexpression of the DNA repair protein&nbsp;<em>recA<\/em>.<\/li>\n\n\n\n<li>Decrease in nitroreductase activity.<\/li>\n\n\n\n<li>Adaptations to oxidative stress.<\/li>\n<\/ul>\n\n\n\n<p><strong>In H pylori<\/strong>&nbsp;\u2013<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Mutations in the&nbsp;<em>rdxA<\/em>&nbsp;and&nbsp;<em>frxA<\/em>&nbsp;nitroreductase genes.<\/li>\n\n\n\n<li>Overexpression of&nbsp;<em>recA<\/em>&nbsp;(<strong>protein<\/strong>&nbsp;essential for the repair and maintenance of DNA).<\/li>\n\n\n\n<li>Overexpression of the&nbsp;<em>hefA and TolC<\/em>&nbsp;bacterial efflux pump.<\/li>\n\n\n\n<li>Mutations within the ferric uptake regulator (<em>fur<\/em>) gene, which is responsible for responding to reactive oxygen species and iron uptake [Lynch 2013].<\/li>\n\n\n\n<li>Mutation in&nbsp;<em>rpsU<\/em>&nbsp;gene involved in protein synthesis.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Spectrum<\/h3>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Metronidazole susceptible:<\/strong><\/td><td>Bacteroides, Prevotella, Porphyromonas, Fusobacterium<br>H pylori<br>Clostridium spp, Clostridioides difficile<br>Giardia, Entamoeba, Dientamoeba<br>Trichomonas<\/td><\/tr><tr><td><strong>Variable susceptibility:<\/strong><\/td><td>Veilonella, Suterella, Aggregatibacter actinomycetemcomitans, Campylobacter coli, Campylobacter fetus,<\/td><\/tr><tr><td><strong>Resistant:<\/strong><\/td><td>Mobilincus, Eikenella corrodens, Captocytophaga<br>Actinomyces, Bifidobacterium, Lactobacillus, and Cutibacterium acne.<br>Aerobic bacteria.<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Adverse effects:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Gastrointestinal adverse effects including metallic taste and rarely hepatitis\/pancreatitis.<\/li>\n\n\n\n<li>Hypersensitivity\/allergy.<\/li>\n\n\n\n<li>Neurologic, esp long term use:&nbsp; peripheral neuropathy,&nbsp; ataxia, encephalopathy, tremors, seizures etc.<\/li>\n\n\n\n<li>Others -reversible leukopenia, thrombocytopenia<\/li>\n<\/ul>\n\n\n\n<p><strong>Caution<\/strong>&nbsp;should be exercised when prescribing to a patient with severe hepatic disease, blood dyscrasia and CNS disease (seizure).<br>Concomitant alcohol use may cause a&nbsp;disulfiram reaction.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Indication:<\/strong><\/h3>\n\n\n\n<p><strong>Treatment of Anaerobic Infections<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Intra-abdominal Infections, including peritonitis, intra-abdominal abscess and liver abscess,<\/li>\n\n\n\n<li>Skin and Skin Structure Infections,<\/li>\n\n\n\n<li>Gynecologic Infections, including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection,<\/li>\n\n\n\n<li>Bacterial Septicemia<\/li>\n\n\n\n<li>Bone and Joint Infections, as adjunctive therapy,<\/li>\n\n\n\n<li>Central Nervous System (CNS) Infections, including meningitis and brain abscesses,\u00a0<\/li>\n\n\n\n<li>Lower Respiratory Tract Infections, including pneumonia, empyema, and lung abscess,&nbsp;<\/li>\n\n\n\n<li>Endocarditis caused by Bacteroides<\/li>\n<\/ul>\n\n\n\n<p><strong>Surgical Prophylaxis<\/strong><\/p>\n\n\n\n<p><strong>C difficile-associated diarrhoea<\/strong><\/p>\n\n\n\n<p>[Ref:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/018890s052lbl.pdf]<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>PK\/PD:<\/strong><\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Lipophilic. Low protein binding. Moderate\/ large volume of distribution.<\/li>\n\n\n\n<li>Concentration-dependent killing.<\/li>\n\n\n\n<li>Penetrates most tissue, including CSF (higher concentration is achieved if the meninges is inflamed). Good penetration in the abscess.<br>The concentration in stool is higher in patients with diarrhoea and decreases as the diarrhoea settles.<br>The concentration in bile in obstructive cholecystitis is low.<\/li>\n\n\n\n<li>T1\/2 = 8 hours<\/li>\n\n\n\n<li>Oral bioavailability \u2013 almost 100%<\/li>\n\n\n\n<li>It should be taken with food \u2013 food does not alter bioavailability.<\/li>\n\n\n\n<li><strong>Metabolism:<\/strong>\u00a0<strong>Liver \u2013\u00a0<\/strong><em>some metabolites have antimicrobial activity. It enters enterohepatic circulation.<br>Half-life is increased in liver impairment, and dose adjustment is necessary.<\/em><\/li>\n\n\n\n<li><strong>Excretion:<\/strong>&nbsp;Urine (60 to 80% of the dose); faecal excretion accounting for 6 to 15% of the dose [<a href=\"https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2010\/012623s061lbl.pdf\">FDA<\/a>]<\/li>\n<\/ul>\n\n\n\n<p><strong>Pregnancy:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Pregnancy Category B, Crosses placenta, secreted in breast milk.<\/li>\n\n\n\n<li>Teratogenic in the first trimester.<\/li>\n\n\n\n<li>Breastfeeding \u2013 The manufacturer advises avoiding large single doses of metronidazole though otherwise compatible<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Class:&nbsp;Nitroimidazole.Mol weight:&nbsp;171First used in 1960. Mechanism of action: Metronidazole enters the susceptible (bacterial\/parasite) cells by passive diffusion. It gets&nbsp;activated to [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":174,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ngg_post_thumbnail":0,"footnotes":""},"categories":[9],"tags":[28,40],"class_list":["post-173","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-antibiotic","tag-antibiotic","tag-metronidazole"],"_links":{"self":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/173","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=173"}],"version-history":[{"count":1,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/173\/revisions"}],"predecessor-version":[{"id":175,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/posts\/173\/revisions\/175"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=\/wp\/v2\/media\/174"}],"wp:attachment":[{"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=173"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=173"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/microregistrar.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=173"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}