Mecillinam or amdinocillin (USAN

United States Adopted Name

United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

), trade name Coactin, is an extended-spectrum penicillin

Penicillin

Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 that binds specifically to penicillin binding protein 2

Penicillin binding proteins

Penicillin-binding proteins are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered...

 (PBP2), and is only considered to be active against Gram-negative bacteria. It is used primarily in the treatment of urinary tract infection

Urinary tract infection

A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...

s, and has also been used to treat typhoid

Typhoid fever

Typhoid fever, also known as Typhoid, is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feces of an infected person, which contain the bacterium Salmonella enterica, serovar Typhi...

 and paratyphoid fever

Paratyphoid fever

Paratyphoid fevers or Enteric fevers are a group of enteric illnesses caused by serotypic strains of the Salmonella genus of bacteria, S. Paratyphi....

. Because mecillinam has very low oral bioavailability

Bioavailability

In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

, an orally-active prodrug

Prodrug

A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...

 was developed: pivmecillinam

Pivmecillinam

Pivmecillinam or amdinocillin pivoxil is an orally-active prodrug of mecillinam, an extended-spectrum penicillin antibiotic. Pivmecillinam is the pivaloyloxymethyl ester of mecillinam...

. Neither drug is available in the United States.

History

With the codename FL 1060, mecillinam was developed by the Danish pharmaceutical company

Pharmaceutical company

The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...

 Leo Pharmaceutical Products (now LEO Pharma). It was first described in the scientific literature in a 1972 paper.

Activity

Mecillinam is active against most pathogenic Gram-negative bacteria, except Pseudomonas aeruginosa

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...

and some species of Proteus

Proteus (bacterium)

Proteus is a genus of Gram-negative Proteobacteria.-Clinical significance:Three species—P. vulgaris, P. mirabilis, and P. penneri—are opportunistic human pathogens. Proteus includes pathogens responsible for many human urinary tract infections. P. mirabilis causes wound and urinary...

. Several studies have also found it to be as effective as other antibiotics for treating Staphylococcus saprophyticus

Staphylococcus saprophyticus

Staphylococcus saprophyticus is a coagulase-negative species of Staphylococcus bacteria. S. saprophyticus is often implicated in urinary tract infections. S. saprophyticus is resistant to the antibiotic novobiocin, a characteristic that is used in laboratory identification to distinguish it from S...

infection, even though it is Gram-positive, possibly because mecillinam reaches very high concentrations in urine.

Worldwide resistance

Antibiotic resistance

Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 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

Escherichia coli

Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

) to 5.2% (Proteus mirabilis

Proteus mirabilis

Proteus mirabilis is a Gram-negative, facultatively anaerobic, rod shaped bacterium. It shows swarming motility, and urease activity. P. mirabilis causes 90% of all Proteus infections in humans.-Diagnosis:...

). Another large study conducted in Europe and Brazil

Brazil

Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

 obtained similar results — 95.9% of E. coli strains, for instance, were sensitive to mecillinam.

Adverse effects

The adverse effect

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

 profile of mecillinam is similar to that of other penicillins. The most common side effects of mecillinam use are rash

Rash

A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

 and gastrointestinal upset, including nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

 and vomiting

Vomiting

Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

.