Fosfomycin is a drug from the class of antibiotics. The substance is mainly used to treat severe bacterial infections.
What is fosfomycin?
The antibiotic fosfomycin was first isolated in 1970 in Alicante, Spain, from bacteria of the genus Streptomyces.Antibiotics are metabolic products of bacteria or fungi that can inhibit the growth of other microorganisms. Fosfomycin is a bactericidal antibiotic. This means that it not only inhibits the growth of bacteria, but also kills them.
Fosfomycin is available for intravenous use in the form of a sodium salt. This form of application, bypassing the intestines, is particularly suitable for the treatment of very severe acute and chronic infections. Granules for oral use are also available in the form of the salt fosfomycin trometamol. This is more used to treat uncomplicated infections.
Pharmacological effect
Fosfomycin is one of the so-called epoxy antibiotics. Epoxies are very reactive organic compounds. The antibiotic inhibits the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, also known as MurA for short. MurA is an important part of murein biosynthesis. Mureines are macromolecules made up of sugars and amino acids. They are the most important components of the cell wall of many types of bacteria and serve to stabilize the bacterium. When the murein coat breaks down, the bacteria burst and perish.
Fosfomycin disrupts the first step in murein biosynthesis. In the process, an enolpyruvyl unit is actually transferred from the substance phosphoenolpyruvate to UDP-N-acetylglucosamine. By blocking this important step, the murein layer of the bacteria is destroyed and they die.
Medical application & use
The main indication for fosfomycin is severe bacterial infections caused by germs sensitive to fosfomycin. This includes, for example, osteomyelitis. This is an infectious inflammation of the bone marrow that often occurs after an open bone fracture or surgery on the skeleton. Meningitis can also be treated with fosfomycin. Meningitis is inflammation of the membranes of the brain and spinal cord, which are part of the central nervous system. Because of its proximity to the brain and spinal cord, bacterial meningitis is always life-threatening and therefore a medical emergency that must be treated as quickly as possible.
Fosfomycin is also used to treat inflammation of the soft tissues, skin, biliary tract, and airways. Other indications are blood poisoning, inflammation of the inner lining of the heart (endocarditis) and infections that affect the eyes, throat or nose. Fosfomycin is also administered orally for uncomplicated urinary tract infections in women.
Overall, fosfomycin is effective against both gram-negative and gram-positive pathogens. Good effectiveness against Haemophilus influenzae, Escherichia coli, some Proteus species, Citrobacter, streptococci and staphylococci is considered to be proven. Because of these active properties, fosfomycin is also often used in the clinical field for nosocomial infections. Some Bacteroides species and the majority of the indole-positive strains of the Proteus bacteria, however, are resistant to fosfomycin. Cross resistance has not yet been described.
For more severe infections, fosfomycin is often combined with other bactericidal antibiotics. In particular in combination with ß-lactam antibiotics such as penicillin or cefazolin, synergistic effects can be achieved. There are also synergies when combined with moxifloxacin, linezolid and quinupristin.
Risks & side effects
Fosfomycin has been shown to be well tolerated in animal experiments. Side effects tend to occur rarely, but then particularly affect the gastrointestinal tract. Possible side effects are vomiting, diarrhea, loss of appetite and taste irritation. Occasionally, rashes are observed as a hypersensitivity reaction. Furthermore, taking fosfomycin can lead to dizziness, tiredness, increased liver values, headache and shortness of breath. The sodium levels in the blood may be increased (hypernatremia), but the potassium levels may be decreased (hypokalaemia).
If the kidney function is impaired, the dose of fosfomycin must be adjusted. In elderly patients, dose adjustments should be based on creatinine clearance. Particular caution is required in patients with cardiac insufficiency and a tendency to edema. The increased sodium intake from fosfomycin can result in increased potassium excretion. Such hypokalemia can have dangerous consequences for patients at risk. For example, they can develop life-threatening cardiac arrhythmias, which in the worst case can also end in a heart attack.
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