Fosfomycin: Difference between revisions

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

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.

@@ Line 10: / Line 10: @@
 *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
+*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 ===
+===Breakpoints===
-* Determined by agar (not broth) dilution
+*Determined by agar (not broth) dilution
-* [[Enterobacterales]]: susceptible if MIC ≤32, resistance if MIC >32
+*[[Enterobacterales]]: susceptible if MIC ≤32, resistance if MIC >32
-* [[Pseudomonas aeruginosa]]: no MIC breakpoints; ECV is 128 mg/L
+*[[Pseudomonas aeruginosa]]: no MIC breakpoints; ECV is 128 mg/L
-* [[Acinetobacter]]: no MIC breakpoints or ECV
+*[[Acinetobacter]]: no MIC breakpoints or ECV
 ==Dosing==
@@ Line 28: / Line 32: @@
 *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[[CiteRef::antonello2021fo]]
+=== 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==
@@ Line 38: / Line 57: @@
 *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]]