Fosfomycin

Background

Mechanism of Action

• Inhibits an enzyme-catalyzed reaction in cell wall synthesis
• Bacteridical

Spectrum of Activity

• Active against many Gram-positive bacteria, including MSSA, MRSA, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, and VRE
• Active against many Gram-negative bacteria, including regular Enterobacterales, CRE, and ESBL
  • Unclear if effective against Pseudomonas
• Limited activity against gut anaerobes, but does cover Peptostreptococcus

PK/PD

• Efficacy predicted by time-above-MIC

Breakpoints

• Determined by agar (not broth) dilution
• Enterobacterales: susceptible if MIC ≤32, resistance if MIC >32
• Pseudomonas aeruginosa: no MIC breakpoints; ECV is 128 mg/L
• Acinetobacter: no MIC breakpoints or ECV

Dosing

• Uncomplicated UTI: fosfomycin 3 g PO once
• Complicated UTI: fosfomycin 3 g PO q72h for 2 to 3 doses

Safety

Monitoring

• Hypokalemia, high sodium content, dose-limiting nausea, vomiting, and diarrhea

Pregnancy

• Safe in pregnancy