Fosfomycin: Difference between revisions

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*Active against many Gram-positive bacteria, including MSSA, MRSA, [[Staphylococcus epidermidis]], [[Streptococcus pneumoniae]], [[Enterococcus faecalis]], [[Enterococcus faecium]], and [[VRE]]
  
*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
  
*Active against many Gram-negative bacteria, including regular [[Enterobacterales]], CRE, and ESBL
  +
**Includes [[Salmonella]], [[Shigella]], [[E. coli]], [[Klebsiella]], [[Enterobacter]], [[Serratia]], [[Citrobacter]], and [[Proteus mirabilis]]
 
**Unclear if effective against [[Pseudomonas]]
  
**Unclear if effective against [[Pseudomonas]]
 
*Limited activity against gut anaerobes, but does cover [[Peptostreptococcus]]
  
*Limited activity against gut anaerobes, but does cover [[Peptostreptococcus]]
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*Intrinsic resistance in [[Pseudomonas]] (probably), [[Acinetobacter]], [[Stenotrophomonas maltophilia]], [[Burkholderia cepacia]], some [[coagulase-negative staphylococci]] ([[Staphylococcus capitis]] and [[Staphylococcus saprophyticus]]), [[Morganella morganii]], and [[Mycobacterium tuberculosis]]
   
 
===PK/PD===
  
===PK/PD===
   
−
*Efficacy predicted by time-above-MIC
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*Efficacy predicted by time above MIC
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*Oral bioavailability 34 to 58%; higher if taken on an empty stomach
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*Elimination half-life of 5.7 hours, 93 to 99% excreted unchanged in the urine
   
−
=== Breakpoints ===
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===Breakpoints===
   
−
* Determined by agar (not broth) dilution
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*Determined by agar (not broth) dilution
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* [[Enterobacterales]]: susceptible if MIC ≤32, resistance if MIC >32
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*[[Enterobacterales]]: susceptible if MIC ≤32, resistance if MIC >32
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* [[Pseudomonas aeruginosa]]: no MIC breakpoints; ECV is 128 mg/L
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*[[Pseudomonas aeruginosa]]: no MIC breakpoints; ECV is 128 mg/L
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* [[Acinetobacter]]: no MIC breakpoints or ECV
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*[[Acinetobacter]]: no MIC breakpoints or ECV
   
 
==Dosing==
  
==Dosing==
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*Uncomplicated UTI: fosfomycin 3 g PO once
  
*Uncomplicated UTI: fosfomycin 3 g PO once
 
*Complicated UTI: fosfomycin 3 g PO q72h for 2 to 3 doses
  
*Complicated UTI: fosfomycin 3 g PO q72h for 2 to 3 doses
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*Intravenous: fosfomycin disodium 8 g IV q12h
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*CNS or other severe infection: fosfomycin disodium 8 to 12 g IV q12h
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*Continuous infusion may result in better PK/PD: 8 g IV load followed by 16-24 g continuous infusion over 24 hours[[CiteRef::antonello2021fo]]
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  +
=== Renal Dosing ===
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  +
* Oral: no dosage adjustment necessary for oral, though elimination may be prolonged
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* Intravenous
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** CrCl >=130 mL/min: maximum indicated dose for indication (up to 24 g/day in 3 to 4 divided doses)
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** CrCl 40-129 mL/min: normal dose, in 2 to 4 divided doses
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** CrCl 30-39: 70-80% of normal daily dose, in 2 to 3 divided doses
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** CrCl 20-29: 50-70% of normal daily dose, in 2 to 3 divided doses
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** CrCl 10-19: 30-50% of normal daily dose, in 2 to 3 divided doses
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** CrCl <10: 20% of normal daily dose, in 1 to 2 divided doses
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** Intermittent hemodialysis: 2 g after each session (up to 4 g for severe or less susceptible infections)
   
 
==Safety==
  
==Safety==
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*Safe in pregnancy
  
*Safe in pregnancy
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  +
== Further Reading ==
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  +
* Fosfomycin. ''Clin Microbiol Rev''. 2016 Apr;29(2):321-47. doi: [https://doi.org/10.1128/CMR.00068-15 10.1128/CMR.00068-15]. PMID: [https://pubmed.ncbi.nlm.nih.gov/26960938/ 26960938]; PMCID: [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4786888/ PMC4786888].
   
 
[[Category:Antibiotics]]
  
[[Category:Antibiotics]]

Latest revision as of 12:45, 19 September 2024

Background

Mechanism of Action

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

Spectrum of Activity

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

  • Safe in pregnancy

Further Reading

References

  1. ^  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.

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