Pharmacotherapeutic group: Antibacterials for systemic use – other antibacterials.
ATC code: J01XX01
Mechanism of action:
Fosfomycin exerts a bactericidal effect on proliferating pathogens by preventing the enzymatic synthesis of the bacterial cell wall. Fosfomycin inhibits the first stage of intracellular bacterial cell wall synthesis by blocking peptidoglycan synthesis.
Fosfomycin is actively transported into the bacterial cell via two different transport systems (the sn-glycerol-3-phosphate and hexose-6 transport systems).
Pharmacokinetic/pharmacodynamic relationship
Limited data indicate that fosfomycin most likely acts in a time-dependent manner.
Mechanism of resistance
Main mechanism of resistance is a chromosomal mutation causing an alteration of the bacterial fosfomycin transport systems. Further resistance mechanisms, which are plasmid- or transposon-borne, cause enzymatic inactivation of fosfomycin by binding the molecule to glutathione or by cleavage of the carbon-phosphorus-bond in the fosfomycin molecule, respectively.
Cross-resistance
Cross-resistance between fosfomycin and other antibiotic classes is not known.
Susceptibility testing breakpoints
The susceptibility breakpoints established by the European Committee on Antimicrobial Susceptibility Testing are as follows (EUCAST breakpoint table version 11):
Species | susceptible | resistant |
Enterobacterales | ≤ 8 mg/L | > 8 mg/L |
Prevalence of acquired resistance
The prevalence of acquired resistance of individual species may vary geographically and over time. Local information about the resistance situation is therefore necessary, particularly in order to ensure appropriate treatment of severe infections.
The following table is based on data from surveillance programs and studies. It comprises organisms relevant for the approved indications:
Commonly susceptible species
Aerobic Gram-negative microorganisms
Escherichia coli
Species in which acquired resistance may be a problem
Aerobic Gram-positive microorganisms
Enterococcus faecalis
Aerobic Gram-negative microorganisms
Klebsiella pneumonia
Proteus mirabilis
Inherently resistant species
Aerobic Gram-positive microorganisms
Staphylococcus saprophyticus