Mecillinam Explained

Mecillinam (INN) or amdinocillin (USAN) is an extended-spectrum penicillin antibiotic of the amidinopenicillin class that binds specifically to penicillin binding protein 2 (PBP2),^[1] 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.^{[2] [3]} 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.^[4] 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, though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine.

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).^[6] Another large study conducted in Europe and Brazil obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam.^[7]

Adverse effects

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

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.^{[8] [9]}

References

Notes and References

1. Neu HC . Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use . Pharmacotherapy . 5 . 1 . 1–10 . 1985 . 3885172 . 10.1002/j.1875-9114.1985.tb04448.x . 46561080 .
2. Clarke PD, Geddes AM, McGhie D, Wall JC . Mecillinam: a new antibiotic for enteric fever . British Medical Journal . 2 . 6026 . 14–15 . July 1976 . 820402 . 1687648 . 10.1136/bmj.2.6026.14 .
3. Geddes AM, Clarke PD . The treatment of enteric fever with mecillinam . The Journal of Antimicrobial Chemotherapy . 3 . Suppl B . 101–102 . July 1977 . 408321 . 10.1093/jac/3.suppl_b.101 .
4. 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 . 6 . [National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients] . de . Der Urologe. Ausg. A . 50 . 2 . 153–169 . February 2011 . 21312083 . 10.1007/s00120-011-2512-z . 115699373 . National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients .
5. Web site: Amdinocillin (Mecillinam) . Pham P, Bartlett JG . August 28, 2008 . Point-of-Care Information Technology ABX Guide . . September 1, 2008 . https://web.archive.org/web/20090204193527/http://prod.hopkins-abxguide.org/antibiotics/antibacterial/pcn_others/amdinocillin__mecillinam_.html . February 4, 2009 . dead . Retrieved on August 31, 2008. Freely available with registration.
6. Kahlmeter G . 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 . January 2003 . 12493789 . 10.1093/jac/dkg028 . free .
7. Naber KG, Schito G, Botto H, Palou J, Mazzei T . 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 . November 2008 . 18511178 . 10.1016/j.eururo.2008.05.010 .
8. Lund F, Tybring L . 6 -amidinopenicillanic acids--a new group of antibiotics . Nature . 236 . 66 . 135–137 . April 1972 . 4402006 . 10.1038/236135c0 . 4293996 . free .
9. Tybring L, Melchior NH . Mecillinam (FL 1060), a 6beta-amidinopenicillanic acid derivative: bactericidal action and synergy in vitro . Antimicrobial Agents and Chemotherapy . 8 . 3 . 271–276 . September 1975 . 170856 . 429305 . 10.1128/aac.8.3.271 .