Pivmecillinam (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

), or amdinocillin pivoxil (

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to t ...

), sold under the brand name Selexid and Pivya among others, is an orally active

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

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), and is only considered to be active against Gram-negative bacter ...

, an extended-spectrum

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

. Pivmecillinam is the

pivaloyloxymethyl Pivaloyloxymethyl (POM, pivoxil, pivoxyl) is a protecting group used in organic synthesis. The POM radical (chemistry), radical has the formula (CH3)3C-CO-O-CH2. The POM group is also sometimes used to produce prodrugs. For example, the POM grou ...

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of mecillinam. The most common side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

Medical uses

In the US, pivmecillinam is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of female adults with uncomplicated urinary tract infections caused by susceptible isolates of ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'', ''

Proteus mirabilis ''Proteus mirabilis'' is a Gram-negative, facultatively Anaerobic organism, anaerobic, rod-shaped bacterium. It shows swarming motility and urease activity. ''P. mirabilis'' causes 90% of all ''Proteus (bacterium), Proteus'' infections in human ...

'', and ''

Staphylococcus saprophyticus ''Staphylococcus saprophyticus'' is a Gram-positive coccus belonging to the genus ''Staphylococcus''. ''S. saprophyticus'' is a common cause of community-acquired urinary tract infections. History ''Staphylococcus saprophyticus'' was not recogni ...

''. Pivmecillinam is primarily active against

Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

, and is used primarily in the treatment of lower

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

s. In the

Nordic countries The Nordic countries (also known as the Nordics or ''Norden''; ) are a geographical and cultural region in Northern Europe, as well as the Arctic Ocean, Arctic and Atlantic Ocean, North Atlantic oceans. It includes the sovereign states of Denm ...

, it has been widely used in that indication since the 1970s.

Activity

Adverse effects

The

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

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

rash A rash is a change of the skin that 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, cracke ...

and gastrointestinal upset, including

and

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. Retrieved on 31 August 2008. Prodrugs that release pivalate anions when broken down by the body — such as pivmecillinam, pivampicillin and cefditoren pivoxil — have long been known to deplete levels of

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for f ...

. This is not due to the drug itself, but to the pivalate anion, which is mostly removed from the body by forming a conjugate with carnitine. Although short-term use of these drugs can cause a marked decrease in blood levels of carnitine, it is unlikely to be of clinical significance; long-term use, however, appears problematic and is not recommended.

History

The efficacy of pivmecillinam in treating females eighteen years of age or older with uncomplicated UTIs was assessed in three controlled clinical trials comparing different pivmecillinam dosing regimens to

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

, to another oral antibacterial drug and to

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

(an anti-inflammatory drug). The primary measure of efficacy for the three trials was the composite response rate, which included clinical cure (resolution of the symptoms of the uncomplicated UTI that were present in participants at trial entry and no new symptoms) and microbiological response (demonstration that the bacteria cultured from participants' urine at trial entry was reduced). The composite response rate was assessed approximately 8 to 14 days after participants were enrolled into the studies. In the clinical trial comparing pivmecillinam to placebo, 62% of the 137 participants who received pivmecillinam achieved the composite response compared to 10% of the 134 who received placebo. In the clinical trial comparing pivmecillinam to another oral antibacterial drug, 72% of the 127 participants who received pivmecillinam achieved composite response compared to 76% of the 132 who received the comparator drug. In the clinical trial comparing pivmecillinam to ibuprofen, 66% of the 105 participants who received pivmecillinam achieved composite response compared to 22% of the 119 who received ibuprofen. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) granted the application for pivmecillinam

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

and qualified infectious disease product designations. The FDA granted the approval of Pivya to Utility Therapeutics Ltd.

Research

Pivmecillinam has been proposed as the first-line drug of choice for empirical treatment of acute

cystitis A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra ( urethritis) while upper urinary tract infections affect the kidney (py ...

. It has also been used to treat

paratyphoid fever Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of three types of '' Salmonella enterica''. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradu ...

and shigellosis.

References

{{Authority control Penicillins Azepanes Prodrugs Formals