Mecillinam

Mecillinam (INN) or amdinocillin (USAN) is an extended-spectrum penicillin antibiotic of the amidinopenicillin class 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.

Mecillinam

Clinical data
Trade names	Coactin, Leo, Selexid, Selexidin
AHFS/Drugs.com	International Drug Names
Pregnancy category	Appears safe in pregnancy[1]
Routes of administration	Intravenous, intramuscular
ATC code	J01CA11 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Negligible
Protein binding	5 to 10%
Metabolism	Some hepatic metabolism
Elimination half-life	1 to 3 hours
Excretion	Renal and biliary, mostly unchanged
Identifiers
IUPAC name (2S,5R,6R)-6-[(E/Z)-(Azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
CAS Number	32887-01-7 Y
PubChem CID	36273
DrugBank	DB01163 Y
ChemSpider	33357 N
UNII	V10579P3QZ
KEGG	D02888 N
ChEMBL	ChEMBL530 Y
CompTox Dashboard (EPA)	DTXSID3022584
ECHA InfoCard	100.046.601
Chemical and physical data
Formula	C15H23N3O3S
Molar mass	325.43 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)N=CN3CCCCCC3)C(=O)O)C
NY (what is this?)  (verify)

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.^[5] Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa and some species of Proteus.^[6] 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.^[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 from 1.2% (Escherichia coli) to 5.2% (Proteus mirabilis).^[7] Another large study conducted in Europe and Brazil obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam.^[8]

Adverse effects

See also: Beta-lactam antibiotic: Adverse effects

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

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.^[9][10]