Fosfomycin is a novel class ofantibiotic with a chemical structure unrelated to other known antibiotics. It is a bactericidal medication that disrupts cell wall synthesis by inhibiting phosphoenolpyruvate synthetase and thus interferes with the production of peptidoglycan.
In the United States, fosfomycinis available only as a powder formulation of fosfomycin tromethamine, which can be dissolved in liquid and taken orally. Outside the United States, IV formulations are available.
Pharmacokinetics of Fosfomycin
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,fosfomycin 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 outside the Untied States 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 activity against both gram-positive and gram-negative organisms, including some antibiotic-resistant organisms such as
Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA)
Enterococcus species, including vancomycin-resistant enterococci (VRE)
Escherichia coli, including extended-spectrum beta-lactamase (ESBL)–producing and fluoroquinolone-resistant E. coli
Oral fosfomycin should be used only for uncomplicated (ie, lower) urinary tract infections caused byE. colior enterococci. However, IV fosfomycin (when available) is sometimes used to treat infections with multidrug-resistant organisms at other anatomic sites.
Oral fosfomycin is not recommended for treatment of most non-E. coli, Enterobacterales, or Pseudomonas species even in the setting of uncomplicated lower urinary tract infections (1). Furthermore, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) does not endorse susceptibility breakpoints for IV fosfomycin against P. aeruginosa (2).
Indications references
1. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin Infect Dis. Published online July 18, 2023. doi:10.1093/cid/ciad428
2. European Committee on Antimicrobial Susceptibility Testing (EUCAST): Clinical breakpoints - breakpoints and guidance. Accessed April 15, 2024.
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 of Fosfomycin 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 offosfomycin) dissolved in liquid is used. A longer treatment course is probably necessary for infections at other sites.
