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Fosfomycin

By Hans P. Schlecht, MD, MSc, Department of Medicine, Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine ; Christopher Bruno, MD, Division of infectious Diseases & HIV Medicine, Drexel University College of Medicine

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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.

Pharmacology

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.

Indications

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.

Contraindications

There are no significant contraindications to its use other than known hypersensitivity to fosfomycin or to any component of the formulation.

Adverse Effects

Fosfomycin is generally well-tolerated and has a low rate of adverse effects, which include mainly GI symptoms (eg, nausea, diarrhea).

Dosing Considerations

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).

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • THAM
  • VANCOCIN
  • MONUROL

* This is the Professional Version. *