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
Limited activity against gut anaerobes, but does cover Peptostreptococcus
Intrinsic resistance in Pseudomonas Acinetobacter Stenotrophomonas maltophilia Burkholderia cepacia , some coagulase-negative staphylococci (Staphylococcus capitis and Staphylococcus saprophyticus Morganella morganii 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 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
Continuous infusion may result in better PK/PD: 8 g IV load followed by 16-24 g continuous infusion over 24 hours1 Renal Dosing Oral: no dosage adjustment necessary for oral, though elimination may be prolonged
Intravenous
CrCl >=130 mL/min: maximum indicated dose for indication (up to 24 g/day in 3 to 4 divided doses)
CrCl 40-129 mL/min: normal dose, in 2 to 4 divided doses
CrCl 30-39: 70-80% of normal daily dose, in 2 to 3 divided doses
CrCl 20-29: 50-70% of normal daily dose, in 2 to 3 divided doses
CrCl 10-19: 30-50% of normal daily dose, in 2 to 3 divided doses
CrCl <10: 20% of normal daily dose, in 1 to 2 divided doses
Intermittent hemodialysis: 2 g after each session (up to 4 g for severe or less susceptible infections) Safety Monitoring Hypokalemia, high sodium content, dose-limiting nausea, vomiting, and diarrhea Pregnancy Further Reading References
^ Roberta Maria Antonello, Stefano Di Bella, Alberto Enrico Maraolo, Roberto Luzzati. Fosfomycin in continuous or prolonged infusion for systemic bacterial infections: a systematic review of its dosing regimen proposal from in vitro, in vivo and clinical studies. European Journal of Clinical Microbiology & Infectious Diseases . 2021;40(6):1117-1126. doi :10.1007/s10096-021-04181-x .
