Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections.

[8] Fosfomycin was discovered in 1969 and approved for medical use in the United States in 1996 [globalize][8][10] It is on the World Health Organization's List of Essential Medicines.

[18] Intravenous fosfomycin is being increasingly used for treating infections caused by multidrug-resistant bacteria, mostly as a partner drug in order to avoid the occurrence of resistances and to take advantage of its synergistic activity with several other antimicrobials.

[20] Fosfomycin demonstrated strong antibiofilm activity in both in vitro and in vivo studies, including prosthetic material infections.

Activity against extended-spectrum β-lactamase-producing pathogens, notably ESBL-producing E. coli, is good to excellent, because the drug is not affected by cross-resistance issues.

These enzymes function by nucleophilic attack on carbon 1 of fosfomycin, which opens the epoxide ring and renders the drug ineffective.

[citation needed] The enzymes differ by the identity of the nucleophile used in the reaction: glutathione for FosA, bacillithiol for FosB,[28][29] and water for FosX.

[27] FosC uses ATP and adds a phosphate group to fosfomycin, thus altering its properties and making the drug ineffective.

[31] This enzyme catalyzes the committed step in peptidoglycan biosynthesis, namely the ligation of phosphoenolpyruvate (PEP) to the 3'-hydroxyl group of UDP-N-acetylglucosamine.

Fosfomycin is a PEP analog that inhibits MurA by alkylating an active site cysteine residue (Cys 115 in the Escherichia coli enzyme).

[34] Fosfomycin (originally known as phosphonomycin) was discovered in a joint effort of Merck and Co. and Spain's Compañía Española de Penicilina y Antibióticos (CEPA).