Fosfomycin: Difference between revisions

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== Background ==
==Background==


=== Mechanism of Action ===
===Mechanism of Action===


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


=== Spectrum of Activity ===
===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-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]]
*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
*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


== Dosing ==
===Breakpoints===


*Determined by agar (not broth) dilution
⚫
* Uncomplicated UTI: fosfomycin 3 g PO once
*[[Enterobacterales]]: susceptible if MIC ≤32, resistance if MIC >32
⚫
* Complicated UTI: fosfomycin 3 g PO q72h for 2 to 3 doses
*[[Pseudomonas aeruginosa]]: no MIC breakpoints; ECV is 128 mg/L
*[[Acinetobacter]]: no MIC breakpoints or ECV


== Safety ==
==Dosing==


⚫
*Uncomplicated UTI: fosfomycin 3 g PO once
⚫
=== Monitoring ===
⚫
*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 hours[[CiteRef::antonello2021fo]]


=== Renal Dosing ===
⚫
* Hypokalemia, high sodium content, dose-limiting nausea, vomiting, and diarrhea


* Oral: no dosage adjustment necessary for oral, though elimination may be prolonged
⚫
=== Pregnancy ===
* 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==
⚫
* Safe in pregnancy

⚫
===Monitoring===

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

⚫
===Pregnancy===

⚫
*Safe in pregnancy

== Further Reading ==

* 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]]

Latest revision as of 17:45, 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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