The
antimicrobial agent fosfomycin was discovered in 1969, at a time when bacteria had not yet developed extended-spectrum β-lactamases or carbapenemases. Decades later, it is not uncommon for gram-negative organisms to be multidrug-resistant and even pan-resistant to available
antibiotic regimens, leaving clinicians with few therapeutic alternatives. Because
fosfomycin has been shown to retain activity against these virulent pathogens, there is renewed interest in its use as a therapeutic agent.
Fosfomycin formulations including
fosfomycin disodium and the newer
tromethamine salt are less toxic than other alternatives and are attractive options for resistant gram-negative and gram-positive
infections. Oral
fosfomycin tromethamine is approved for
urinary tract infections in the United States, and an intravenous formulation is also available outside of the United States for systemic disease. The bactericidal action of
fosfomycin occurs at an earlier step in cell wall synthesis than that of β-
lactam antibiotics. From an in vitro standpoint,
fosfomycin generally has high activity against ESBL- and carbapenemase-producing Enterobacteriaceae; multidrug-resistant Pseudomonas aeruginosa susceptibility appears to be more dependent on the local antibiogram.
Fosfomycin formulations have a large volume of distribution, penetrate biofilms, and concentrate in the urine. Both oral and intravenous
fosfomycin formulations are effective for a wide range of gram-negative
infections and disease severities; however, clinical studies are limited.
Fosfomycin formulations are well-tolerated, and mild gastrointestinal distress is the most common adverse effect. The primary limitations of
fosfomycin are the lack of established regimens for complicated
infections and the lack of availability of the intravenous formulation in the United States. Further study of this promising agent seems warranted in the current climate of antibiotic resistance.