Fosfomycin is a drug belonging to the class of active substances known as antibiotics. The substance is used primarily to treat severe bacterial infections.
What is fosfomycin?
Fosfomycin is a drug belonging to the class of active substances known as antibiotics. The substance is used primarily to treat serious bacterial infections. The antibiotic fosfomycin was first isolated from bacteria of the genus Streptomyces in 1970 in Alicante, Spain. 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 intestine, is particularly suitable for the treatment of very severe acute and chronic infections. A granulate in the form of the salt fosfomycin-trometamol is also available for oral use. This is used more for the treatment of uncomplicated infections.
Pharmacologic action
Fosfomycin belongs to the group of antibiotics known as epoxides. Epoxides are highly reactive organic compounds. The antibiotic inhibits the enzyme UDP-N-acetylglucosamine-enolpyruvyl-transferase, or MurA for short. MurA is an important part of murein biosynthesis. Mureins are macromolecules composed of sugars and amino acids. They are the major components of the cell wall of many bacterial species and serve to stabilize the bacterium. When the murein coat of bacteria is dissolved, they burst and perish. Fosfomycin disrupts the first step in murein biosynthesis. This actually involves the transfer of an enolpyruvyl unit 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 and use
The main indication for fosfomycin is severe bacterial infections caused by fosfomycin-susceptible germs. These include osteomyelitis, for example. This is an infectious inflammation of the bone marrow that often occurs after open fractures or surgery on the skeleton. Meningitis can also be treated with fosfomycin. Meningitis is an inflammation of the membranes of the brain and spinal cord, which are part of the central nervous system. Bacterial meningitis is always life-threatening because of its proximity to the brain and spinal cord, making it a medical emergency that must be treated as soon as possible. Furthermore, fosfomycin is also used to treat inflammation of the soft tissues, skin, biliary tract and respiratory tract. Other indications include blood poisoning, inflammation of the inner lining of the heart (endocarditis) and infections affecting the eye, throat or nose. Fosfomycin is also administered orally for uncomplicated urinary tract infections in women. Overall, fosfomycin is well effective against both Gram-negative and Gram-positive pathogens. Good efficacy against Haemophilus influenzae, Escherichia coli, some Proteus species, Citrobacter, Streptococci, and Staphylococci is considered established. Because of these efficacy properties, Fosfomycin is also frequently used in clinical settings for nosocomial infections. In contrast, some Bacteroides species and the majority of indole-positive strains of Proteus bacteria are resistant to fosfomycin. Cross-resistance has not yet been described. In more severe infections, fosfomycin is often combined with other antibiotics with bactericidal activity. In particular, synergistic effects can be achieved in combination with ß-lactam antibiotics such as penicillin or cefazolin. Synergistic effects are also seen when combined with moxifloxacin, linezolid, and quinupristin.
Risks and side effects
In animal studies, fosfomycin has been shown to be well tolerated. Side effects occur rather rarely, but then affect the gastrointestinal tract in particular. Accordingly, possible side effects include vomiting, diarrhea, loss of appetite, and taste irritation. Occasionally, exanthema is observed as a hypersensitivity reaction. Furthermore, dizziness, fatigue, elevated liver enzymes, headache, and shortness of breath may occur while taking fosfomycin. Blood sodium levels may be increased (hypernatremia), while potassium levels may be decreased (hypokalemia).In case of impaired renal performance, the dose of fosfomycin must be adjusted. In elderly patients, dose adjustment should be based on creatinine clearance. Special caution should be exercised in patients with heart failure and a tendency to edema. Increased potassium excretion may follow from increased sodium intake with fosfomycin. Such hypokalemia can have dangerous consequences for high-risk patients. For example, they may develop life-threatening cardiac arrhythmias, which in the worst case may end in myocardial infarction.
