Fosfomycin

  • (2R, 3S )-3- Methyloxiranphosphonsäure IUPAC
  • (1R, 2S )-cis -(1,2- epoxypropyl ) phosphonic acid
  • Phosphomycin
  • 23155-02-4 ( Fosfomycin )
  • 78964-85-9 ( fosfomycin trometamol )
  • 26016-98-8 ( Fosfomycin calcium salt · · monohydrate)
  • 26016-99-9 ( · fosfomycin disodium salt)

J01XX01

Antibiotic

~ 94 ° C ( Fosfomycin )

Soluble in water

Disodium salt

> 10 g · kg -1 ( LD50, rat, oral)

Template: Infobox chemical / molecular formula search available

Fosfomycin is a drug ( antibiotic), which is used in human medicine for serious bacterial infections. Fosfomycin was established in 1970 in Alicante ( Spain) isolated from Streptomyces.

Application

Fosfomycin is in the form of the sodium salt for intravenous application. The parenteral route of administration is indicated for the treatment of severe, acute and chronic infections if these are caused by fosfomycinempfindliche pathogens. Fosfomycin is particularly indicated when penicillins and cephalosporins may not be given and their effectiveness is not sufficient due to the localization of infection and sensitivity of the pathogen. Fosfomycin is usually given as part of combination therapy, particularly in the treatment of multi-resistant germs.

In the form of better absorbable salt Fosfomycin trometamol there is also a granulate which is approved for oral use for an uncomplicated urinary tract infection woman ( Eindosisbehandlung; absorption about 40 %). In the current S3 guideline for the treatment of uncomplicated urinary tract infections is due to the favorable resistance profile recommended as the first choice for the treatment of uncomplicated cystitis.

Efficacy / activity spectrum

By disturbance of murein synthesis in the cell wall of the bacteria, it is bactericidal. It has good activity against the following bacteria:

  • Gram-negative Haemophilus influenzae
  • Escherichia coli (including ESBL )
  • Citrobacter
  • Some Proteus species
  • Gram-positive Staphylococci (including MRSA )
  • Streptococci ( S. pyogenes, S. pneumoniae)

Mechanism of Action

Fosfomycin is an epoxy antibiotic. It is an irreversible inhibitor of the enzyme MurA (UDP -N -acetylglucosamine transferase enolpyruvyl ). MurA catalyzes the first step of murein biosynthesis: the transfer of a Enolpyruvyleinheit from phosphoenolpyruvate ( PEP ) to UDP-N- acetylglucosamine ( UNAG ). The products of the reaction are enolpyruvyl - UDP-N- acetylglucosamine and phosphate. Fosfomycin alkylating the thiol group of a cysteine ​​residue ( Cys -115, E. coli numbering Mura), which has an important role in catalysis.

Resistance

Most of indole -positive Proteus strains are resistant to fosfomycin. Against Bacteroides species of the drug is ineffective.

Application

Indications

The medicament is used for bacterial infections caused by germs fosfomycinempfindliche. This can be a osteomyelitis, meningitis, urinary tract infection, a, airway inflammation, inflammation of the skin and soft tissues, infection of the biliary tract, sepsis, endocarditis or oto-, rhino -, Laryngologic and ophthalmic infections.

Synergism

If a combination with other antibiotics is medically indicated, the use of a bactericidal other antibiotic is recommended. In vitro studies show that can be achieved by the combination of fosfomycin with β -lactam antibiotics, such as penicillin, ampicillin, cefazolin, carbapenems, additive to synergistic effects in general. Combinations with substances that are active against staphylococci ( linezolid, quinupristin / dalfopristin, moxifloxacin ), also act synergistically.

Restrictions on use

  • Dose reduction in renal performance
  • Dose adjustment in elderly patients with creatinine clearance
  • Monitoring of serum electrolytes ( for regular usage in patients with heart failure, tendency to edema or secondary hyperaldosteronism ) because of the increased sodium intake ( 14.5 mM / g fosfomycin ). The increased sodium intake can increase the excretion of potassium and potassium losses cause (see hypokalemia).

Side effects

The drug is well tolerated in animal experiments. The rate of side effects is low. Side effects occur in particular in the area of the gastrointestinal tract.

Occasionally eruptions, acute hypersensitivity reactions, vomiting, loss of appetite, diarrhea, phlebitis, irritating taste, transient increase in liver enzymes, shortness of breath, headache, dizziness, fatigue, hypernatremia, hypokalemia are called. In some cases, it came to vision problems.

Trade names

  • For parenteral use: INFECTOFOS (D)
  • For oral use: Monuril (D, A, CH)
CAS registry number PubChem Anatomical Therapeutic Chemical Classification System DrugBank Dangerous Substances Directive (67/548/EEC) Active ingredient TRIS Medical guideline Peptidoglycan Renal failure Exanthem
343490
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