{{short description|Pharmaceutical drug}} {{cs1 config|name-list-style=vanc}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 403346583 | IUPAC_name = (2''S'',5''R'',6''R'')-6-[(''E''/''Z'')-(Azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid | image = Mecillinam skeletal formula.svg | image_class = skin-invert-image | image2 = Mecillinam ball-and-stick model from xtal 1981.png | image_class2 = bg-transparent | drug_name = <!--Clinical data--> | tradename = Coactin, Leo, Selexid, Selexidin | Drugs.com = {{drugs.com|international|amdinocillin}} | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = Appears safe in pregnancy<ref name=Nicolle>{{cite journal | vauthors = Nicolle LE | title = Pivmecillinam in the treatment of urinary tract infections | journal = The Journal of Antimicrobial Chemotherapy | volume = 46 | issue = Suppl A | pages = 35–39 | date = August 2000 | pmid = 10969050 | doi = 10.1093/jac/46.suppl_1.35 | doi-access = free }}</ref> | legal_AU = S4 | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = POM | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_status = Rx-only | routes_of_administration = Intravenous, intramuscular <!--Pharmacokinetic data--> | bioavailability = Negligible | protein_bound = 5 to 10% | metabolism = Some hepatic metabolism | elimination_half-life = 1 to 3 hours | excretion = Renal and biliary, mostly unchanged <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 32887-01-7 | CAS_supplemental = | ATC_prefix = J01 | ATC_suffix = CA11 | ATC_supplemental = | PubChem = 36273 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01163 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 33357 | UNII_Ref = {{fdacite|changed|FDA}} | UNII = V10579P3QZ | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = D02888 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 530 <!--Chemical data--> | C=15 | H=23 | N=3 | O=3 | S=1 | smiles = CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)N=CN3CCCCCC3)C(=O)O)C }} '''Mecillinam''' (INN) or '''amdinocillin''' (USAN) is an extended-spectrum penicillin antibiotic of the amidinopenicillin class that binds specifically to penicillin binding protein 2 (PBP2),<ref name=Neu>{{cite journal | vauthors = Neu HC | title = Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use | journal = Pharmacotherapy | volume = 5 | issue = 1 | pages = 1–10 | year = 1985 | pmid = 3885172 | doi = 10.1002/j.1875-9114.1985.tb04448.x | s2cid = 46561080 }}</ref> and is only considered to be active against Gram-negative bacteria. It is used primarily in the treatment of urinary tract infections, and has also been used to treat typhoid and paratyphoid fever.<ref>{{cite journal | vauthors = Clarke PD, Geddes AM, McGhie D, Wall JC | title = Mecillinam: a new antibiotic for enteric fever | journal = British Medical Journal | volume = 2 | issue = 6026 | pages = 14–15 | date = July 1976 | pmid = 820402 | pmc = 1687648 | doi = 10.1136/bmj.2.6026.14 }}</ref><ref>{{cite journal | vauthors = Geddes AM, Clarke PD | title = The treatment of enteric fever with mecillinam | journal = The Journal of Antimicrobial Chemotherapy | volume = 3 | issue = Suppl B | pages = 101–102 | date = July 1977 | pmid = 408321 | doi = 10.1093/jac/3.suppl_b.101 }}</ref> Because mecillinam has very low oral bioavailability, an orally active prodrug was developed: pivmecillinam.
==Medical uses== Mecillinam is used in the treatment of infections due to susceptible gram-negative bacteria, especially urinary tract infections which are most commonly caused by ''Escherichia coli''.<ref>{{cite journal | vauthors = Wagenlehner FM, Schmiemann G, Hoyme U, Fünfstück R, Hummers-Pradier E, Kaase M, Kniehl E, Selbach I, Sester U, Vahlensieck W, Watermann D, Naber KG | display-authors = 6 | title = [National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients] | language = de | journal = Der Urologe. Ausg. A | volume = 50 | issue = 2 | pages = 153–169 | date = February 2011 | pmid = 21312083 | doi = 10.1007/s00120-011-2512-z | s2cid = 115699373 | trans-title = National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients }}</ref> Mecillinam is active against most pathogenic Gram-negative bacteria, except ''Pseudomonas aeruginosa'' and some species of ''Proteus''.<ref name=POC-IT>{{cite web |url=http://prod.hopkins-abxguide.org/antibiotics/antibacterial/pcn_others/amdinocillin__mecillinam_.html |title=Amdinocillin (Mecillinam) |vauthors=Pham P, Bartlett JG |date=August 28, 2008 |work=Point-of-Care Information Technology ABX Guide |publisher=Johns Hopkins University |access-date=September 1, 2008 |archive-url=https://web.archive.org/web/20090204193527/http://prod.hopkins-abxguide.org/antibiotics/antibacterial/pcn_others/amdinocillin__mecillinam_.html |archive-date=February 4, 2009 |url-status=dead }} Retrieved on August 31, 2008. Freely available with registration.</ref> Several studies have also found it to be as effective as other antibiotics for treating ''Staphylococcus saprophyticus'' infection, though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine.<ref name=Nicolle/>
Worldwide resistance to mecillinam in bacteria causing urinary tract infection has remained very low since its introduction; a 2003 study conducted in 16 European countries and Canada found resistance to range from 1.2% (''Escherichia coli'') to 5.2% (''Proteus mirabilis'').<ref>{{cite journal | vauthors = Kahlmeter G | title = An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project | journal = The Journal of Antimicrobial Chemotherapy | volume = 51 | issue = 1 | pages = 69–76 | date = January 2003 | pmid = 12493789 | doi = 10.1093/jac/dkg028 | doi-access = free }}</ref> Another large study conducted in Europe and Brazil obtained similar results — 95.9% of ''E. coli'' strains, for instance, were sensitive to mecillinam.<ref>{{cite journal | vauthors = Naber KG, Schito G, Botto H, Palou J, Mazzei T | title = Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy | journal = European Urology | volume = 54 | issue = 5 | pages = 1164–1175 | date = November 2008 | pmid = 18511178 | doi = 10.1016/j.eururo.2008.05.010 }}</ref>
==Adverse effects== {{see also|Β-lactam antibiotic#Adverse_effects|l1=Beta-lactam antibiotic: Adverse effects}} The adverse effect profile of mecillinam is similar to that of other penicillins.<ref name=Neu/> Its most common side effects are rash and gastrointestinal upset, including nausea and vomiting.<ref name=Nicolle/>
==History== With the codename FL 1060, mecillinam was developed by the Danish pharmaceutical company Leo Pharmaceutical Products (now LEO Pharma). It was first described in the scientific literature in a 1972 paper.<ref>{{cite journal | vauthors = Lund F, Tybring L | title = 6 -amidinopenicillanic acids--a new group of antibiotics | journal = Nature | volume = 236 | issue = 66 | pages = 135–137 | date = April 1972 | pmid = 4402006 | doi = 10.1038/236135c0 | s2cid = 4293996 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tybring L, Melchior NH | title = Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro | journal = Antimicrobial Agents and Chemotherapy | volume = 8 | issue = 3 | pages = 271–276 | date = September 1975 | pmid = 170856 | pmc = 429305 | doi = 10.1128/aac.8.3.271 }}</ref>
== References == {{Reflist}} {{Clear}} {{Beta-lactam antibiotics}}
Category:Penicillins Category:Enantiopure drugs Category:Azepanes