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]] |
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*Active against many Gram-negative bacteria, including regular [[Enterobacterales]], CRE, and ESBL |
*Active against many Gram-negative bacteria, including regular [[Enterobacterales]], CRE, and ESBL |
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**Includes [[Salmonella]], [[Shigella]], [[E. coli]], [[Klebsiella]], [[Enterobacter]], [[Serratia]], [[Citrobacter]], and [[Proteus mirabilis]] |
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**Unclear if effective against [[Pseudomonas]] |
**Unclear if effective against [[Pseudomonas]] |
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*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 [[Acinetobacter]], [[Stenotrophomonas maltophilia]], [[Burkholderia cepacia]], some [[coagulase-negative staphylococci]] ([[Staphylococcus capitis]] and [[Staphylococcus saprophyticus]]), [[Morganella morganii]], and [[Mycobacterium tuberculosis]] |
*Intrinsic resistance in [[Pseudomonas]] (probably), [[Acinetobacter]], [[Stenotrophomonas maltophilia]], [[Burkholderia cepacia]], some [[coagulase-negative staphylococci]] ([[Staphylococcus capitis]] and [[Staphylococcus saprophyticus]]), [[Morganella morganii]], and [[Mycobacterium tuberculosis]] |
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===PK/PD=== |
===PK/PD=== |
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*Intravenous: fosfomycin disodium 8 g IV q12h |
*Intravenous: fosfomycin disodium 8 g IV q12h |
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*CNS or other severe infection: fosfomycin disodium 8 to 12 g IV q12h |
*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 === |
=== Renal Dosing === |
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* Oral: no dosage adjustment necessary for oral, though elimination may be prolonged |
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* CrCl 40 to 80 mL/min: normal dose |
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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 |
** CrCl 40-129 mL/min: normal dose, in 2 to 4 divided doses |
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* CrCl |
** CrCl 30-39: 70-80% 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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==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]. |
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[[Category:Antibiotics]] |
[[Category:Antibiotics]] |
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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
- 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
- Includes Salmonella, Shigella, E. coli, Klebsiella, Enterobacter, Serratia, Citrobacter, and Proteus mirabilis
- Unclear if effective against Pseudomonas
- 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
- 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
- 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
- Fosfomycin. Clin Microbiol Rev. 2016 Apr;29(2):321-47. doi: 10.1128/CMR.00068-15. PMID: 26960938; PMCID: PMC4786888.
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.
