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
• Intrinsic resistance in Acinetobacter, Stenotrophomonas maltophilia, Burkholderia cepacia, some coagulase-negative staphylococci (Staphylococcus capitis and Staphylococcus saprophyticus), Morganella morganii, and Mycobacterium tuberculosis

PK/PD

• Efficacy predicted by time above MIC
• Oral bioavailability 34 to 58%; higher if taken on an empty stomach
• Elimination half-life of 5.7 hours, 93 to 99% excreted unchanged in the urine

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
• Intravenous: fosfomycin disodium 8 g IV q12h
• CNS or other severe infection: fosfomycin disodium 8 to 12 g IV q12h

Renal Dosing

• No dosage adjustment necessary for oral, though elimination may be prolonged
• CrCl 40 to 80 mL/min: normal dose
• CrCl 31-40: 70% of normal daily dose
• CrCl 21-30: 60% of normal daily dose
• CrCl 11-20: 40% of normal daily dose
• CrCl ≤10: 20% of normal daily dose
• Intermittent hemodialysis: 2 g after each session

Safety

Monitoring

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

Pregnancy

• Safe in pregnancy