Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: ZAMBON S.p.A., Via Lillo Del Duca, 10, 20091 Bresso (Milan) ā Italy, Tel: +39 02 665 241, Fax: +39 02 665 01 492
Pharmacotherapeutic group: Antibacterials for systemic use – other antibacterials
ATC code: J01XX01
Fosfomycin acts on at the first stage of bacterial wall synthesis. It inhibits the phosphoenolpyruvate transferase enzyme, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate. Fosfomycin is actively transported into the bacterial cell via two different transport systems (the sn-glycerol-3-phosphate and hexose-6 transport systems). It can also reduce bacterial adhesion to bladder mucosa, which can be a predisposing factor for recurring infections. Its mechanism of action explains the lack of cross-resistance with other antibiotics.
Commonly susceptible species:
Citrobacter spp
Escherichia coli
Klebsiella oxytoca
Proteus mirabilis
Staphylococcus aureus
Species in which acquired resistance may be a problem:
Enterococcus faecalis
Enterobacter cloacae
Pseudomonas aeruginosa
Serratia marcescens
Inherently resistant species:
Bacteroides spp.
Main mechanism of resistance is a chromosomal mutation causing an alteration of the bacterial fosfomycin transport systems.
EUCAST clinical MIC breakpoints for oral fosfomycin to separate susceptible (S) pathogens from resistant ® pathogens are:
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable.
Limited data indicate that fosfomycin most likely acts in a time-dependent manner.
After single-dose oral administration, fosfomycin trometamol has an absolute bioavailability of about 34-41%. Rate and extent of absorption are reduced by food.
Fosfomycin is distributed to tissues including the kidneys and bladder wall. Fosfomycin is not bound to plasma proteins and crosses the placental barrier.
Fosfomycin does not appear to be metabolised and is excreted unchanged mainly via the kidneys by glomerular filtration with an elimination half-life of about 4 hours after oral administration.
In patients with impaired renal function, the elimination half-life is increased proportionally to the degree of renal insufficiency.
In older people fosfomycin clearance is reduced in line with the age related reduction in renal function.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or toxicity to reproduction.
No carcinogenicity data are available for fosfomycin trometamol.
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