Fosfomycin: Resurgence of an old companion

Fosfomycin was discovered over four decades ago, yet has drawn renewed interest as an agent active against a range of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens. Its unique mechanism of action and broad spectrum of activity makes it a promising candidate in the treatment of various MDR/XDR infections. There has been a surge of in vitro data on its activity against MDR/XDR organisms, both when used as a single agent and in combination with other agents. In the United States, fosfomycin is only approved in an oral formulation for the treatment of acute uncomplicated urinary tract infections (UTIs), whereas in some countries both oral and intravenous formulations are available for various indications. Fosfomycin has minimal interactions with other medications and has a relatively favorable safety profile, with diarrhea being the most common adverse reaction. Fosfomycin has low protein binding and is excreted primarily unchanged in the urine. The clinical outcomes of patients treated with fosfomycin are favorable for uncomplicated UTIs, but data are limited for use in other conditions. Fosfomycin maintains activity against most Enterobacteriaceae including Escherichia coli, but plasmid-mediated resistance due to inactivation have appeared in recent years, which has the potential to compromise its use in the future. In this review, we summarize the current knowledge of this resurgent agent and its role in our antimicrobial armamentarium.