Exelfos Mechanism of Action

ATC Code: J01XX01. Other antibacterials.
Pharmacology: Pharmacodynamics: Mechanism of action: Fosfomycin trometamol is an antibiotic with a broad spectrum of activity, derivate from phosphonic acid.
Fosfomycin bactericidal effect consists in block wall cellular synthesis. The specific mechanism inhibiting enolpyruvyl transferase avoid cross resistances with other antibiotics.
Relationship between pharmacokinetics and pharmacodynamics: Relationship between pharmacokinetics and pharmacodynamics of Fosfomycin trometamol has not been established.
The drug activity depends substantially on the period when the concentration of the active ingredient is above the minimum inhibitory concentration (MIC) of the bacterial agent.
Mechanisms of resistance: A resistance to fosfomycin can be based on the following mechanisms: Fosfomycin is admitted into the bacterial cell actively via two different transport systems (glycerin-3-phosphate and hexose-6 transport system). In Enterobacteriaceae the glycerin-3-phosphate transport system can be changed in such a way that fosfomycin is no longer transported into the cell.
Another plasmid-encoded mechanism occurring in Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. is based on the presence of a specific protein, under the effect of which fosfomycin metabolises and is bound to glutathione (GSH).
In staphylococci a plasmid-encoded fosfomycin resistance also occurs. The exact mechanism of the resistance has not yet been determined.
A cross-resistance of fosfomycin with other antibiotics classes is not known.
Limit values: The testing of fosfomycin is performed using the routine dilution series. The evaluation of the results is performed on the basis of the limit values for fosfomycin. The following minimum inhibitory concentrations for susceptible and resistant germs were established: See table.

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Microbiological sensibility: Fosfomycin is active in front of Gram-positive and Gram-negative microorganisms strain penicillinases producers included, and usual urinary pathogen agents like Escherichia coli, Proteus, Klebsiella, Enterobacter, Staphylococcus, Streptococcus, and other resistant strains.
Organisms intrinsically resistant: S. saprophyticus.
Pharmacokinetics: Absorption: Fosfomycin trometamol is well absorbed by oral administration, achieving therapeutic urinary concentrations until 36 hours after single dose.
Distribution: After administration of 2 or 3 g of fosfomycin it is obtained the following plasmatic concentration 20-30 mcg/ml.
Elimination: Fosfomycin is excreted unchanged mainly into the urine. High urinary levels (about 3000 mcg/ml) are rapidly reached within 2-4 hours, and last for at least 36 hours.
In patients with moderately reduced renal function (Creatinine clearance - CrCl <80 ml/min), including the physiological reduction in the elderly, the half-life of fosfomycin is slightly prolonged but urinary concentration remains therapeutically adequate.
Toxicology: Preclinical safety data: Fosfomycin trometamol potential toxic effect does not differ from calcium and sodium fosfomycin.
There is no evidence that fosfomycin has teratogenic effect in different animal species, neither in fertility studies.
Fosfomycin trometamol mutagenic and carcinogenic studies have negative results.