Fosfomycin: Difference between revisions
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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 species]], [[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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| − | *Efficacy predicted by time |
+ | *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 |
| − | * |
+ | *[[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== |
==Dosing== |
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*Uncomplicated UTI: fosfomycin 3 g PO once |
*Uncomplicated UTI: fosfomycin 3 g PO once |
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*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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| + | |||
| + | === Renal Dosing === |
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| + | |||
| + | * CrCl 40 to 80 mL/min: normal dose |
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| + | * CrCl 31-40: 70% of normal daily dose |
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| + | * CrCl 21-30: 60% of normal daily dose |
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| + | * CrCl 11-20: 40% of normal daily dose |
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| + | * CrCl ≤10: 20% of normal daily dose |
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| + | * Intermittent hemodialysis: 2 g after each session |
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==Safety== |
==Safety== |
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Revision as of 16:00, 29 August 2020
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
- Unclear if effective against Pseudomonas
- Limited activity against gut anaerobes, but does cover Peptostreptococcus
- Intrinsic resistance in Acinetobacter species, 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
Renal Dosing
- CrCl 40 to 80 mL/min: normal dose
- CrCl 31-40: 70% of normal daily dose
- CrCl 21-30: 60% of normal daily dose
- CrCl 11-20: 40% of normal daily dose
- CrCl ≤10: 20% of normal daily dose
- Intermittent hemodialysis: 2 g after each session
Safety
Monitoring
- Hypokalemia, high sodium content, dose-limiting nausea, vomiting, and diarrhea
Pregnancy
- Safe in pregnancy
