fosfomycinbased

Fosfomycinbased refers to regimens and products that rely on fosfomycin, a bactericidal antibiotic that disrupts early cell wall synthesis. Fosfomycinbased therapies are used to treat a range of infections, most prominently urinary tract infections, and are explored for certain resistant pathogens.

Mechanism and pharmacology: Fosfomycin inhibits the MurA enzyme, blocking formation of peptidoglycan in the bacterial cell wall. It is taken up into bacteria via the GlpT and UhpT transporters, contributing to its broad spectrum. In humans, fosfomycin is administered orally as a trometamol salt for outpatient use or intravenously as a disodium salt in hospital settings. The drug achieves very high urinary concentrations and distributes to many tissues, with renal excretion as a major elimination route.

Spectrum and resistance: Fosfomycinbased activity covers many Gram-negative rods, including Escherichia coli and some Klebsiella species, and also shows activity against certain Gram-positive organisms such as Enterococcus and Staphylococcus aureus. Activity against Pseudomonas and some anaerobes is variable. Resistance can arise through mutations that reduce drug uptake (glpT or uhpT), alterations in the MurA target, or plasmid-encoded enzymes like fosA that inactivate fosfomycin. Resistance emergence underscores the need for susceptibility testing and appropriate stewardship.

Clinical use and administration: Oral fosfomycin trometamol is widely used for uncomplicated cystitis, typically as a single 3-gram dose. For complicated urinary tract infections or more serious infections, intravenous fosfomycin disodium is used with dosing adjusted for renal function and clinical context. Safety is generally favorable, with gastrointestinal side effects and headaches being the most common; electrolyte disturbances may occur with IV administration.

Regulation and research: Fosfomycinbased regimens are supported by regulatory approvals for specific indications in various regions. Ongoing research evaluates combinations with beta-lactams or other agents and explores expanded uses in resistant infections.