Fosfomycin: Difference between revisions
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+ | ==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]] |
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| − | ** |
+ | **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]] |
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| − | === |
+ | ===PK/PD=== |
| − | * |
+ | *Efficacy predicted by time above MIC |
| + | *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 |
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| − | == |
+ | ===Breakpoints=== |
| + | *Determined by agar (not broth) dilution |
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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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| + | *[[Acinetobacter]]: no MIC breakpoints or ECV |
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| − | == |
+ | ==Dosing== |
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| + | *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<ref>Antonello RM, Di Bella S, Maraolo AE, Luzzati R. 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. Eur J Clin Microbiol Infect Dis. 2021 Jun;40(6):1117-1126. doi: [https://doi.org/10.1007/s10096-021-04181-x 10.1007/s10096-021-04181-x]. Epub 2021 Feb 18. PMID: 33604721; PMCID: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139892/ PMC8139892].</ref> |
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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) |
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| + | ==Safety== |
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| ⚫ | |||
| + | |||
| ⚫ | |||
| + | |||
| ⚫ | |||
| + | |||
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| + | |||
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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]] |
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Latest revision as of 13:41, 21 July 2023
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 hours[1]
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.
- ↑ Antonello RM, Di Bella S, Maraolo AE, Luzzati R. 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. Eur J Clin Microbiol Infect Dis. 2021 Jun;40(6):1117-1126. doi: 10.1007/s10096-021-04181-x. Epub 2021 Feb 18. PMID: 33604721; PMCID: PMC8139892.
