Pivmecillinam is indicated for the treatment of infections caused by mecillinam-sensitive organisms, including acute cystitis, complicated urinary tract infections, salmonellosis, shigellosis, enteropathogenic E. coli diarrhoea, Gram-negative septicaemia, and biliary tract infections.

Pivmecillinam belongs to a new class of penicillin called amidinopenicillins. It is a prodrug of mecillinam that allows oral administration. The prodrug itself has no antibacterial activity, but it is converted into the active form through enzymatic hydrolysis during absorption in the gastrointestinal tract.

Pivmecillinam is bactericidal in action. It inhibits bacterial cell wall synthesis, but its site of action is different from other penicillins. It is highly active against Enterobacteriaceae, including E. coli, Klebsiella, Proteus, Enterobacter, Salmonella, Shigella, and Yersinia. It has poor activity against Gram-positive organisms, limited activity against Pseudomonas aeruginosa, and virtually no activity against Enterococcus faecalis.

Adults:

• The usual dose: 1-2 tablets 3 times daily according to severity of the infection.
• In acute uncomplicated cystitis: initially 400 mg then 200 mg every 8 hours for 3 days.
• In chronic or recurrent bacteriurea: 400 mg 6-8 hours.
• For the treatment of salmonellosis (including enteric fever): 1.2-2.4 gm daily for 14 days. To eliminate salmonella carriage, therapy may be prolonged for 2-4 weeks. In complicated urinary tract infection the usual treatment time is 1-2 weeks.
• For prophylactic treatment of recurrent urinary tract infections: 1 tablet every evening is recommended.

Children:

• Weighing less than 20 kg should be given 20-60 mg/kg divided into 3-4 daily doses. Those weighing more than 20 kg should receive normal adult dose.
• In shigellosis: 20 mg/kg 4 times a day for 5 days.
• For UTI: 20-40 mg/kg/day in 3-4 divided doses.
• For salmonellosis: 30-60 mg/kg/day in 3-4 divided doses.

The tablet should be taken with at least 50-100 ml fluid. As the bioavailability is practically unaffected by simultaneous food intake, This tablets are best taken with or immediately after a meal.

There are no confirmed reports of cross-allergy to Pivmecillinam in patients with a known history of hypersensitivity to penicillins or cephalosporins. However, until more clinical experience is available, it is advisable to avoid using Pivmecillinam in such patients.

Pivmecillinam is generally well tolerated, including in patients with impaired renal function. Gastrointestinal side effects such as nausea, vomiting, diarrhoea, or indigestion may occur, especially when taken on an empty stomach. Skin rashes have been reported occasionally, but the typical ampicillin rash has not been observed. There is no evidence of hepato-, nephro-, or ototoxicity. Although not reported, the possibility of anaphylaxis cannot be completely excluded.

Mecillinam levels equivalent to about one-third of serum concentration have been detected in the umbilical cord, and small amounts have been found in amniotic fluid. Therefore, use of Pivmecillinam during pregnancy should be avoided. Mecillinam is not excreted into breast milk of lactating mothers.

As with other antibiotics eliminated mainly via the kidneys, repeated dosing in patients with impaired renal function may lead to increased blood levels of mecillinam.

In patients with renal impairment, the initial dose and dosing interval usually do not require adjustment. However, maintenance dose should be modified as follows:

• CrCl ≥30 ml/min: full dose
• CrCl 10–30 ml/min: 50% dose
• CrCl <10 ml/min: 25% dose

Pivmecillinam should be avoided in infants under 3 months of age.

There is limited experience with overdose. Excessive doses may cause nausea, vomiting, and gastritis. Treatment is mainly symptomatic and supportive. Haemodialysis may help reduce blood levels if necessary.

Mecillinams

Store in a cool, dry place. Protect from light and moisture.