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]] |
===PK/PD=== |
===PK/PD=== |
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Revision as of 13:40, 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
- ↑ 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.
