fosfomycins

Fosfomycins, commonly referred to as fosfomycin, are a class of broad-spectrum antibiotics derived from actinomycetes, notably Streptomyces species. The primary active compound, fosfomycin, is a small phosphonic acid antibiotic that is available as the oral prodrug fosfomycin tromethamine and the intravenous salt fosfomycin disodium.

The mechanism of action involves inhibition of bacterial cell wall synthesis by inactivating MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), the enzyme that catalyzes the first step of peptidoglycan formation. Fosfomycin acts as a substrate analogue of phosphoenolpyruvate and, after uptake by bacterial transporters, forms a covalent adduct with MurA, halting cell wall production and causing bacterial death.

In terms of spectrum, fosfomycins are active against many Gram-negative enteric bacteria, including Escherichia coli and other Enterobacterales, and they also cover some Gram-positive pathogens such as Staphylococcus aureus. Activity against Pseudomonas spp. is limited. Resistance can arise through inactivating enzymes such as fosA in Gram-negatives, or through reduced drug uptake due to loss or alteration of the GlpT and UhpT transporters.

Pharmacokinetics and administration include oral fosfomycin tromethamine, which delivers active fosfomycin and achieves high urinary concentrations, making it effective for urinary tract infections. A common regimen for uncomplicated cystitis is a single 3-gram dose. Intravenous fosfomycin disodium is used for systemic or complicated infections in hospital settings, including infections caused by some resistant organisms.

Safety and regulation: fosfomycin is generally well tolerated; common adverse effects are gastrointestinal upset and headaches. It is excreted renally, so dosing must be adjusted in renal impairment, and coadministration with calcium-containing products may affect absorption of the oral form.