Mecillinam

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Mecillinam
Mecillinam skeletal formula.svg
Mecillinam ball-and-stick model from xtal 1981.png
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
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
  • (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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.601 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H23N3O3S
Molar mass 325.43 g·mol−1
3D model (JSmol)
  • CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)N=CN3CCCCCC3)C(=O)O)C
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

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

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]

References

  1. 1 2 3 Nicolle LE (August 2000). "Pivmecillinam in the treatment of urinary tract infections". The Journal of Antimicrobial Chemotherapy. 46 (Suppl A): 35–39. doi: 10.1093/jac/46.suppl_1.35 . PMID   10969050.
  2. 1 2 Neu HC (1985). "Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use". Pharmacotherapy. 5 (1): 1–10. doi:10.1002/j.1875-9114.1985.tb04448.x. PMID   3885172. S2CID   46561080.
  3. ↑ Clarke PD, Geddes AM, McGhie D, Wall JC (July 1976). "Mecillinam: a new antibiotic for enteric fever". British Medical Journal. 2 (6026): 14–15. doi:10.1136/bmj.2.6026.14. PMC   1687648 . PMID   820402.
  4. ↑ Geddes AM, Clarke PD (July 1977). "The treatment of enteric fever with mecillinam". The Journal of Antimicrobial Chemotherapy. 3 (Suppl B): 101–102. doi:10.1093/jac/3.suppl_b.101. PMID   408321.
  5. ↑ Wagenlehner FM, Schmiemann G, Hoyme U, Fünfstück R, Hummers-Pradier E, Kaase M, et al. (February 2011). "[National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients]" [National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients]. Der Urologe. Ausg. A (in German). 50 (2): 153–169. doi:10.1007/s00120-011-2512-z. PMID   21312083. S2CID   115699373.
  6. ↑ Pham P, Bartlett JG (August 28, 2008). "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University. Archived from the original on February 4, 2009. Retrieved September 1, 2008. Retrieved on August 31, 2008. Freely available with registration.
  7. ↑ Kahlmeter G (January 2003). "An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project". The Journal of Antimicrobial Chemotherapy. 51 (1): 69–76. doi: 10.1093/jac/dkg028 . PMID   12493789.
  8. ↑ Naber KG, Schito G, Botto H, Palou J, Mazzei T (November 2008). "Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy". European Urology. 54 (5): 1164–1175. doi:10.1016/j.eururo.2008.05.010. PMID   18511178.
  9. ↑ Lund F, Tybring L (April 1972). "6 -amidinopenicillanic acids--a new group of antibiotics". Nature. 236 (66): 135–137. doi: 10.1038/236135c0 . PMID   4402006. S2CID   4293996.
  10. ↑ Tybring L, Melchior NH (September 1975). "Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro". Antimicrobial Agents and Chemotherapy. 8 (3): 271–276. doi:10.1128/aac.8.3.271. PMC   429305 . PMID   170856.
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