Fosfomycin is a novel class of antibacterial drugs 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.
Pharmacokinetics
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 urinary tract infections, not pyelonephritis.
Fosfomycin does not bind to plasma proteins and distributes widely into tissues. 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 hours.
An IV formulation of fosfomycin is available in some countries and can be useful for more serious infections, including central nervous system infections, osteomyelitis, and pneumonia; when used to treat these infections, it is often used with other antibiotics such as beta-lactams.
Indications for Fosfomycin
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 species, including vancomycin-resistant enterococci (VRE)
Enterobacterales (formerly Enterobacteriaceae), including extended-spectrum beta-lactamase (ESBL)–producing and carbapenem-resistant Klebsiella pneumoniae
Escherichia coli, including fluoroquinolone-resistant E. coli
Pseudomonas aeruginosa, which has variable rates of resistance
Oral fosfomycin should be used only for uncomplicated (ie, lower) urinary tract infections caused by susceptible pathogens. However, because it has a broad spectrum of activity, IV fosfomycin (when available) is sometimes used to treat infections with multidrug-resistant organisms at other anatomic sites.
Contraindications to Fosfomycin
There are no significant contraindications to its use other than known hypersensitivity to fosfomycin or to any component of the formulation.
Use During Pregnancy and Breastfeeding
Fosfomycin crosses the placenta but is generally considered to be safe for treatment of cystitis in pregnant women.
How much fosfomycin enters breast milk is unknown, and caution is advised if treatment with fosfomycin is necessary for breastfeeding women.
Adverse Effects of Fosfomycin
Fosfomycin is generally well-tolerated and has a low rate of adverse effects, which include mainly gastrointestinal symptoms (eg, nausea, diarrhea).
Dosing Considerations for Fosfomycin
For uncomplicated urinary tract infections in women, a single oral dose of fosfomycin tromethamine 5.61 g (equivalent to 3 g of fosfomycin) dissolved in liquid is used. A longer treatment course is probably necessary for infections at other sites.