Mecillinam

Amdinocillin

Systematic (IUPAC) name
(2S,5R,6R)-6-[(azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	B(US) Appears safe in pregnancy[1]
Legal status	℞ Prescription only
Routes	Intravenous, intramuscular
Pharmacokinetic data
Bioavailability	Negligible
Protein binding	5 to 10%
Metabolism	Some hepatic metabolism
Half-life	1 to 3 hours
Excretion	Renal and biliary, mostly unchanged
Identifiers
CAS number	32887-01-7 Y
ATC code	J01CA11
PubChem	CID 36273
DrugBank	DB01163
ChemSpider	33357 N
UNII	V10579P3QZ N
KEGG	D02888 N
ChEMBL	CHEMBL530 Y
Chemical data
Formula	C15H23N3O3S
Mol. mass	325.426 g/mol
SMILES	eMolecules & PubChem
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Mecillinam (INN) or amdinocillin (USAN), trade name Coactin, is an extended-spectrum penicillin antibiotic that binds specifically to penicillin binding protein 2 (PBP2),^[2] 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.^[3][4] Because mecillinam has very low oral bioavailability, an orally-active prodrug was developed: pivmecillinam. Neither drug is available in the United States.^[5]

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.^[6][7]

Activity

Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa and some species of Proteus.^[5] Several studies have also found it to be as effective as other antibiotics for treating Staphylococcus saprophyticus infection, even though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine.^[1]

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 between 1.2% (Escherichia coli) to 5.2% (Proteus mirabilis).^[8] Another large study conducted in Europe and Brazil obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam.^[9]

Adverse effects

See also: Beta-lactam antibiotic: Adverse effects

The adverse effect profile of mecillinam is similar to that of other penicillins.^[2] The most common side effects of mecillinam use are rash and gastrointestinal upset, including nausea and vomiting.^[1]

References

1. ^ ^{a b c} Nicolle LE (August 2000). = long&pmid = 10969050 "Pivmecillinam in the treatment of urinary tract infections". J Antimicrob Chemother 46 Suppl A (90001): 35–39. doi:10.1093/jac/46.suppl_1.35. PMID 10969050. http://jac.oxfordjournals.org/cgi/pmidlookup?view = long&pmid = 10969050. 
2. ^ ^{a b} Neu HC (1985). "Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use". Pharmacotherapy 5 (1): 1–10. PMID 3885172. 
3. ^ Clarke PD, Geddes AM, McGhie D, Wall JC (July 1976). "Mecillinam: a new antibiotic for enteric fever". Br Med J 2 (6026): 14–5. doi:10.1136/bmj.2.6026.14. PMC 1687648. PMID 820402. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1687648. 
4. ^ Geddes AM, Clarke PD (July 1977). "The treatment of enteric fever with mecillinam". J Antimicrob Chemother 3 Suppl B: 101–2. PMID 408321. 
5. ^ ^{a b} Pham P, Bartlett JG (August 28, 2008). "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. http://prod.hopkins-abxguide.org/antibiotics/antibacterial/pcn_others/amdinocillin__mecillinam_.html.  Retrieved on August 31, 2008. Freely available with registration.
6. ^ Lund F, Tybring L (April 1972). "6β-amidinopenicillanic acids—a new group of antibiotics". Nature New Biol 236 (66): 135–7. doi:10.1038/236135c0. PMID 4402006. 
7. ^ Tybring L, Melchior NH (September 1975). "Mecillinam (FL 1060), a 6β-Amidinopenicillanic Acid Derivative: Bactericidal Action and Synergy In Vitro". Antimicrob Agents Chemother 8 (3): 271–6. PMC 429305. PMID 170856. http://aac.asm.org/cgi/pmidlookup?view=long&pmid=170856. 
8. ^ Kahlmeter G (January 2003). "An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO·SENS Project". J Antimicrob Chemother 51 (1): 69–76. doi:10.1093/jac/dkg028. PMID 12493789. http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12493789. 
9. ^ Naber KG, Schito G, Botto H, Palou J, Mazzei T (May 2008). "Surveillance Study in Europe and Brazil on Clinical Aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): Implications for Empiric Therapy". Eur Urol 54 (5): 1164–75. doi:10.1016/j.eururo.2008.05.010. PMID 18511178.