Fosfomycin Tromethamine, a Broad-Spectrum Bactericidal, Especially for Lower Urinary Tract Infections.

Fosfomycin is a broad-spectrum bactericidal for human and animals purposes, which inhibits the growth of E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc.. Fosfomycin tromethamine is a phosphonic acidepoxide derivative, which expands the therapeutic utility of fosfomycin salt because its water solubility increased enough to allow oral administration. This compound is a white to off-white powder with great hygroscopic and solubility in water.

Mechanism

Fosfomycin tromethamine, is a derivate of fosfomycin, which was initially isolated from fermentationsof streptomyces spp and been used as human medicine and veterinary medicine for over 50 years. Fosfomycin can inactivate the first enzyme in the bacterial cell wall biosynthesis pathway, which occurs through nucleophilic opening of the epoxide ring. Fosfomycin tromethamine only acts on the bacterial cell wall, human cells do not have this target site and is not affected. In this case this compound can be used in pregnant women, children and elderly patients.

Features

• • Broad spectrum antibiotic

Fosfomycin sodium is a broad-spectrum antibiotic of Gram-positive and Gram-negative bacteria, for instance E. coli, S. aureus, Serratia, Klebsiella, Citrobacter, Enterococcus, and Enterobacter etc. and is particularly suitable for the treatment of acute cystitis

• • Rapid sterilization

After oral administration, fosfomycin tromethamine is rapidly decomposed into fosfomycin and tromethamine in the body. With the characteristics of low molecular weight and high hydrophilicity, fosfomycin tromethamine appears good distribution in fluid and strong penetration. So this medicine can widely distribute in body fluid and tissue to increase curative effect. Tromethamine is a weakly osmotic diuretic, which can alkalinize urine and effectively reduces the symptom of urinary tract irritation.

• • Low toxicityand residue of Fosfomycin tromethamine

Bioavailability of Fosfomycin tromethamine by oral administration is from 34% to 41% in healthy adults, 37% in fasting and 30% after eating. It shows little irritation on the body, no acute toxicity and adverse reactions. The maximum plasma concentration was reached within 2 to 2.5 hours after dose, and will be excreted mainly in its original form in urine and feces in 48h.

Sythesis

The synthesis of fosfomycin tromethamine use fosfomycin sodium as an intermediate. Prepare a certain concentration tromethamine-sulfuric acid solution and then it was added to fosfomycin sodium aqueous solution by drop. After that the sodium sulfate solid is precipitated with methanol and the filtrate is crystallized at low temperature with n-butanol to obtain fosfomycin tromethamine.

Fosfomycin Tromethamine Clinical Application

Fosfomycin tromethamine is used for the treatment of acute uncomplicated lower urinary tract infections caused by sensitive bacteria (such as acute cystitis, acute onset of chronic cystitis, acute urethrovesical syndrome, non-specific urethritis, asymptomatic bacteriuria during pregnancy, and urinary tract infections after surgery) and for the prevention of urinary tract infections during surgery and infections caused by diagnostic procedures of the urinary tract.

Usage and dosage

Adults: single-dose treatment, 3g active ingredient per course; Clinical symptoms usually resolve 2 to 3 days after treatment.

For preventing infections caused by surgical procedures and urinary tract care: 6g active ingredient per dose, with first dose taken 3 hours before surgery and second dose taken 24 hours after surgery.

Cautions

The main symptoms of fosfomycin tromethamine were are diarrhea and soft stools, occasional rash and nausea, which will disappear after drug withdrawal.

It is not known whether fosfomycin tromethamine is excreted in human milk, but given the potential for serious adverse effects of fosmycin tromethamine in lactating infants, it should not be administered to lactating women.

The efficacy and safety of fosfomycin tromethamine in children aged 12 years and younger are lack of sufficient and well-designed clinical verification.