Fosfomycin is a novel class of antibacterial with a chemical structure unrelated to other known antibiotics. It is a bactericidal drug that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate synthetase and thus interferes with the production of peptidoglycan.
In the US, it is available only as a powder formulation of fosfomycin tromethamine, which can be dissolved in liquid and taken orally. Outside the US, IV formulations are available.
Fosfomycin is well absorbed orally and penetrates well into tissues, including sequestered sites such as the prostate and CSF.
Oral bioavailability of the fosfomycin tromethamine salt is low (about 40%), and consequently, serum levels are low relative to the minimum inhibitory concentrations (MICs). For this reason, the drug is used to treat uncomplicated lower UTIs, not pyelonephritis.
Fosfomycin is excreted in urine mainly by glomerular filtration without biotransformation. After oral dosing, urinary levels exceed the MICs of susceptible pathogens for over 24 h.
Fosfomycin has a broad spectrum of activity against both gram-positive and gram-negative organisms, including many antibiotic-resistant organisms such as
Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA)
Enterococcus sp, including vancomycin-resistant enterococci (VRE)
Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)–producing K. pneumoniaeand Escherichia coli
Pseudomonas aeruginosa, which has variable rates of intrinsic resistance
Fosfomycin is used mainly for uncomplicated (ie, lower) UTIs caused by E. coli or E. faecalis. However, because it has a broad spectrum of activity, fosfomycin is sometimes used to treat infections with multidrug-resistant organisms at other anatomic sites.
For uncomplicated UTIs, a single oral dose of fosfomycin tromethamine 5.61 g (equivalent to 3 g of fosfomycin) dissolved in liquid is used. 1A longer treatment course is probably necessary for infections at other sites (eg, prostate).
1Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI:Fosfomycin: Use beyond urinary tract and gastrointestinal infections. Clin Infect Dis. 46 (7):1069–1077, 2008.
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