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==Role in disease== {{main|Pathogenic Escherichia coli}}{{Infobox drug | drug_name = | INN = | type = <!-- empty --> | image = | width = | alt = | caption = <!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) --> | licence_EU = <!-- EMA uses INN (or special INN_EMA) --> | DailyMedID = Escherichia coli | licence_US = <!-- FDA may use generic or brand name (generic name preferred) --> | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = | class = | ATCvet = | ATC_prefix = A07 | ATC_suffix = FA03 | ATC_supplemental = <!-- Legal status --> | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_US_comment = | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above --> <!-- Pharmacokinetic data -->| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion = <!-- Identifiers --> | CAS_number = | CAS_supplemental = | PubChem = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | UNII = | KEGG = | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = <!-- Chemical and physical data --> | IUPAC_name = | chemical_formula_ref = | chemical_formula = | C = | H = | Ag = | Al = | As = | Au = | B = | Bi = | Br = | Ca = | Cl = | Co = | F = | Fe = | Gd = | I = | K = | Li = | Mg = | Mn = | N = | Na = | O = | P = | Pt = | S = | Sb = | Se = | Sr = | Tc = | Zn = | charge = | molecular_weight = | molecular_weight_comment = | SMILES = | StdInChI = | StdInChI_comment = | StdInChIKey = | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }} Most ''E. coli'' strains do not cause disease, naturally living in the gut,<ref>{{cite web|url=http://www.mayoclinic.org/diseases-conditions/e-coli/basics/definition/con-20032105|title=E. coli|work=Mayo Clinic|access-date=10 January 2017}}</ref> but virulent strains can cause [[gastroenteritis]], [[Uropathogenic Escherichia coli|urinary tract infections]], [[Meningitis#Bacterial|neonatal meningitis]], hemorrhagic colitis, and [[Crohn's disease]].<ref name="Baumgart_2007">{{cite journal |vauthors=Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R, Orsi RH, Wiedmann M, McDonough P, Kim SG, Berg D, Schukken Y, Scherl E, Simpson KW |date=September 2007 |title=Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum |journal=The ISME Journal |volume=1 |issue=5 |pages=403β18 |bibcode=2007ISMEJ...1..403B |doi=10.1038/ismej.2007.52 |pmid=18043660 |doi-access=free}}</ref> Common signs and symptoms include severe abdominal cramps, diarrhea, hemorrhagic colitis, vomiting, and sometimes fever. In rarer cases, virulent strains are also responsible for bowel necrosis (tissue death) and perforation without progressing to [[hemolytic-uremic syndrome]], [[peritonitis]], [[mastitis]], [[sepsis]], and gram-negative [[pneumonia]]. Very young children are more susceptible to develop severe illness, such as hemolytic uremic syndrome; however, healthy individuals of all ages are at risk to the severe consequences that may arise as a result of being infected with ''E. coli''.<ref name="Todar" /><ref>{{cite journal |vauthors = Lim JY, Yoon J, Hovde CJ |title = A brief overview of ''Escherichia coli'' O157:H7 and its plasmid O157 |journal = Journal of Microbiology and Biotechnology |volume = 20 |issue = 1 |pages = 5β14 |date = January 2010 |pmid = 20134227 |pmc = 3645889 |doi = 10.4014/jmb.0908.08007 }}</ref><ref name="who.int">{{cite web |url=https://www.who.int/mediacentre/factsheets/fs125/en/|title=E. coli |date = 7 February 2018 |work = World Health Organization }}</ref><ref name="cdc.gov">{{cite web |url=https://www.cdc.gov/features/ecoliinfection/ |archive-url = https://web.archive.org/web/20140201082843/https://www.cdc.gov/features/ecoliinfection/ |archive-date = 1 February 2014 |work = U.S. Centers for Disease Control and Prevention |title=E. coli Infection|date=2018-06-15}}</ref> Some strains of ''E. coli'', for example O157:H7, can produce [[Shiga toxin]]. The Shiga toxin causes inflammatory responses in target cells of the gut, leaving behind lesions which result in the bloody diarrhea that is a symptom of a [[Shigatoxigenic and verotoxigenic Escherichia coli|Shiga toxin-producing ''E. coli'']] (STEC) infection. This toxin further causes premature destruction of the red blood cells, which then clog the body's filtering system, the kidneys, in some rare cases (usually in children and the elderly) causing [[hemolytic-uremic syndrome]] (HUS), which may lead to kidney failure and even death. Signs of hemolytic uremic syndrome include decreased frequency of urination, lethargy, and paleness of cheeks and inside the lower eyelids. In 25% of HUS patients, complications of nervous system occur, which in turn causes [[stroke]]s. In addition, this strain causes the buildup of fluid (since the kidneys do not work), leading to [[edema]] around the lungs, legs, and arms. This increase in fluid buildup especially around the lungs impedes the functioning of the heart, causing an increase in blood pressure.<ref>{{cite web |title = Hemolytic uremic syndrome (HUS) |url=http://www.mayoclinic.com/health/hemolytic-uremic-syndrome/DS00876 |work = Mayo Clinic }}</ref><ref name="who.int"/><ref name="cdc.gov"/> [[Pathogenic Escherichia coli#Urinary tract infection|Uropathogenic ''E. coli'' (UPEC)]] is one of the main causes of [[urinary tract infection]]s.<ref name=pre-eminent>{{cite web|title=Uropathogenic Escherichia coli: The Pre-Eminent Urinary Tract Infection Pathogen|url=https://www.novapublishers.com/catalog/product_info.php?products_id=25500&osCsid=3712df5600f98259a8bdc1d9baf202e9|publisher=Nova publishers|access-date=27 November 2013|archive-url=https://web.archive.org/web/20131202232432/https://www.novapublishers.com/catalog/product_info.php?products_id=25500&osCsid=3712df5600f98259a8bdc1d9baf202e9|archive-date=2 December 2013|url-status=dead}}</ref> It is part of the normal microbiota in the gut and can be introduced in many ways. In particular for females, the direction of wiping after defecation (wiping back to front) can lead to fecal contamination of the urogenital orifices. Anal intercourse can also introduce this bacterium into the male urethra, and in switching from anal to vaginal intercourse, the male can also introduce UPEC to the female urogenital system. [[Enterotoxigenic Escherichia coli|Enterotoxigenic ''E. coli'']] (ETEC) is the most common cause of [[traveler's diarrhea]], with as many as 840 million cases worldwide in developing countries each year. The bacteria, typically transmitted through contaminated food or drinking water, adheres to the [[Intestinal epithelium|intestinal lining]], where it secretes either of two types of [[enterotoxins]], leading to watery diarrhea. The rate and severity of infections are higher among children under the age of five, including as many as 380,000 deaths annually.<ref name=Croxen2013>{{cite journal |vauthors = Croxen MA, Law RJ, Scholz R, Keeney KM, Wlodarska M, Finlay BB |title = Recent advances in understanding enteric pathogenic Escherichia coli |journal = Clinical Microbiology Reviews |volume = 26 |issue = 4 |pages = 822β80 |date = October 2013 |pmid = 24092857 |pmc = 3811233 |doi = 10.1128/CMR.00022-13 }}</ref> In May 2011, one ''E. coli'' strain, [[E. coli O104:H4|O104:H4]], was the subject of a [[2011 E. coli O104:H4 outbreak|bacterial outbreak]] that began in [[Germany]]. Certain strains of ''E. coli'' are a major cause of [[foodborne illness]]. The outbreak started when several people in Germany were infected with [[enterohemorrhagic|enterohemorrhagic ''E. coli'' (EHEC)]] bacteria, leading to hemolytic-uremic syndrome (HUS), a medical emergency that requires urgent treatment. The outbreak did not only concern Germany, but also 15 other countries, including regions in North America.<ref>{{cite web|url=http://www.euro.who.int/en/what-we-do/health-topics/emergencies/international-health-regulations/news/news/2011/07/outbreaks-of-e.-coli-o104h4-infection-update-29 |url-status=dead |archive-url=https://web.archive.org/web/20110808155129/http://www.euro.who.int/en/what-we-do/health-topics/emergencies/international-health-regulations/news/news/2011/07/outbreaks-of-e.-coli-o104h4-infection-update-29 |archive-date=8 August 2011 |title=Outbreaks of ''E. coli'' O104:H4 infection: update 29 |date=7 July 2011 |publisher=WHO}}</ref> On 30 June 2011, the German ''Bundesinstitut fΓΌr Risikobewertung (BfR)'' (Federal Institute for Risk Assessment, a federal institute within the German [[Federal Ministry of Food, Agriculture and Consumer Protection]]) announced that seeds of [[fenugreek]] from [[Egypt]] were likely the cause of the EHEC outbreak.<ref>{{cite web|url = http://www.bfr.bund.de/cm/343/samen_von_bockshornklee_mit_hoher_wahrscheinlichkeit_fuer_ehec_o104_h4_ausbruch_verantwortlich.pdf|title = Samen von Bockshornklee mit hoher Wahrscheinlichkeit fΓΌr EHEC O104:H4 Ausbruch verantwortlich|trans-title=Fenugreek seeds with high probability for EHEC O104: H4 responsible outbreak|date = 30 June 2011|publisher = Bundesinstitut fΓΌr Risikobewertung (BfR) (Federal Institute for Risk Assessment) |language = de|access-date = 17 July 2011}}</ref> Some studies have demonstrated an absence of E. ''coli'' in the gut flora of subjects with the metabolic disorder [[Phenylketonuria]]. It is hypothesized that the absence of these normal bacterium impairs the production of the key vitamins B<sub>2</sub> (riboflavin) and K<sub>2</sub> (menaquinone) β vitamins which are implicated in many physiological roles in humans such as cellular and bone metabolism β and so contributes to the disorder.<ref>{{cite journal | vauthors = Al-Zyoud W, Nasereddin A, Aljarajrah H, Saket M | title = Escherichia coli in children with phenylketonuria | journal = New Microbes and New Infections | volume = 32 | pages = 100616 | date = November 2019 | pmid = 31763047 | pmc = 6859276 | doi = 10.1016/j.nmni.2019.100616 }}</ref> '''Carbapenem-resistant ''E. coli''''' '''(carbapenemase-producing ''E. coli'')''' that are resistant to the [[carbapenem]] class of [[antibiotics]], considered the [[Drug of last resort|drugs of last resort]] for such infections. They are resistant because they produce an [[enzyme]] called a [[carbapenemase]] that disables the drug molecule.<ref>{{cite journal | vauthors = Ghaith DM, Mohamed ZK, Farahat MG, Aboulkasem Shahin W, Mohamed HO | title = Colonization of intestinal microbiota with carbapenemase-producing Enterobacteriaceae in paediatric intensive care units in Cairo, Egypt | journal = Arab Journal of Gastroenterology | volume = 20 | issue = 1 | pages = 19β22 | date = March 2019 | pmid = 30733176 | doi = 10.1016/j.ajg.2019.01.002 | s2cid = 73444389 | url = https://zenodo.org/record/6349599 }}</ref> === Incubation period === The time between ingesting the STEC bacteria and feeling sick is called the "incubation period". The incubation period is usually 3β4 days after the exposure, but may be as short as 1 day or as long as 10 days. The symptoms often begin slowly with mild belly pain or non-bloody diarrhea that worsens over several days. HUS, if it occurs, develops an average 7 days after the first symptoms, when the diarrhea is improving.<ref>{{Cite web|url=https://www.cdc.gov/ecoli/general/|title=General Information{{!}} ''E.coli'' |publisher=U.S. Centers for Disease Control and Prevention|access-date=19 April 2017}}</ref> === Diagnosis === Diagnosis of infectious diarrhea and identification of antimicrobial resistance is performed using a [[stool culture]] with subsequent [[antibiotic sensitivity testing]]. It requires a minimum of 2 days and maximum of several weeks to culture gastrointestinal pathogens. The sensitivity (true positive) and specificity (true negative) rates for stool culture vary by pathogen, although a number of [[human pathogen]]s can not be [[microbiological culture|cultured]]. For culture-positive samples, antimicrobial resistance testing takes an additional 12β24 hours to perform. Current [[point of care]] [[molecular diagnostic]] tests can identify ''E. coli'' and antimicrobial resistance in the identified strains much faster than culture and sensitivity testing. Microarray-based platforms can identify specific pathogenic strains of ''E. coli'' and ''E. coli''-specific AMR genes in two hours or less with high sensitivity and specificity, but the size of the test panel (i.e., total pathogens and antimicrobial resistance genes) is limited. Newer [[Metagenomics#Infectious disease diagnosis|metagenomics-based infectious disease diagnostic]] platforms are currently being developed to overcome the various limitations of culture and all currently available molecular diagnostic technologies. ===Treatment=== The mainstay of treatment is the assessment of [[dehydration]] and replacement of fluid and electrolytes. Administration of [[antibiotics]] has been shown to shorten the course of illness and duration of excretion of enterotoxigenic ''E. coli'' (ETEC) in adults in endemic areas and in traveller's diarrhea, though the rate of resistance to commonly used antibiotics is increasing and they are generally not recommended.<ref>{{Cite web|url=https://www.cdc.gov/ecoli/etec.html|title=Enterotoxigenic E. coli (ETEC)|last=US Centers for Disease Control and Prevention|access-date=21 July 2016}}</ref> The antibiotic used depends upon susceptibility patterns in the particular geographical region. Currently, the antibiotics of choice are [[fluoroquinolone]]s or [[azithromycin]], with an emerging role for [[rifaximin]]. Rifaximin, a semisynthetic rifamycin derivative, is an effective and well-tolerated antibacterial for the management of adults with non-invasive traveller's diarrhea. Rifaximin was significantly more effective than placebo and no less effective than [[ciprofloxacin]] in reducing the duration of diarrhea. While rifaximin is effective in patients with ''E. coli''-predominant traveller's diarrhea, it appears ineffective in patients infected with inflammatory or invasive [[enteropathogen]]s.<ref>{{cite journal |vauthors = Al-Abri SS, Beeching NJ, Nye FJ |title = Traveller's diarrhoea |journal = The Lancet. Infectious Diseases |volume = 5 |issue = 6 |pages = 349β60 |date = June 2005 |pmid = 15919621 |doi = 10.1016/S1473-3099(05)70139-0 }}</ref> ===Prevention=== ETEC is the type of ''E. coli'' that most vaccine development efforts are focused on. [[Antibodies]] against the LT and major CFs of ETEC provide protection against LT-producing, ETEC-expressing [[homology (biology)|homologous]] CFs. Oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral, have been developed. There are currently no licensed vaccines for ETEC, though several are in various stages of development.<ref>{{cite journal | vauthors = Bourgeois AL, Wierzba TF, Walker RI | title = Status of vaccine research and development for enterotoxigenic Escherichia coli | journal = Vaccine | volume = 34 | issue = 26 | pages = 2880β86 | date = June 2016 | pmid = 26988259 | doi = 10.1016/j.vaccine.2016.02.076 | doi-access = free }}</ref> In different trials, the rCTB-WC cholera vaccine provided high (85β100%) short-term protection. An oral ETEC vaccine candidate consisting of rCTB and formalin inactivated ''E. coli'' bacteria expressing major CFs has been shown in clinical trials to be safe, immunogenic, and effective against severe [[diarrhoea]] in American travelers but not against ETEC diarrhoea in young children in [[Egypt]]. A modified ETEC vaccine consisting of recombinant ''E. coli'' strains over-expressing the major CFs and a more LT-like hybrid toxoid called LCTBA, are undergoing clinical testing.<ref>{{cite journal | vauthors = Svennerholm AM | title = From cholera to enterotoxigenic Escherichia coli (ETEC) vaccine development | journal = The Indian Journal of Medical Research | volume = 133 | pages = 188β96 | date = February 2011 | issue = 2 | pmid = 21415493 | pmc = 3089050 }}</ref><ref name="Manson's tropical diseases">{{cite book |veditors = Farrar J, Hotez P, Junghanss T, Kang G, Lalloo D, White NJ |title=Manson's Tropical Diseases |date=2013 |publisher=Elsevier/Saunders |location=Oxford |isbn=978-0702053061 |edition=23rd }}</ref> Other proven prevention methods for ''E. coli'' transmission include handwashing and improved sanitation and drinking water, as transmission occurs through fecal contamination of food and water supplies. Additionally, thoroughly cooking meat and avoiding consumption of raw, unpasteurized beverages, such as juices and milk are other proven methods for preventing ''E. coli''. Lastly, cross-contamination of utensils and work spaces should be avoided when preparing food.<ref>{{cite web |url=https://www.cdc.gov/ecoli/general/index.html |title=General Information- ''E.coli'' |publisher=[[Centers for Disease Control and Prevention]] |access-date=25 May 2017}}</ref>
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