Administration of Fosfomycin
Fosfomycin is available in two main formulations: oral fosfomycin tromethamine as a single-dose sachet and intravenous fosfomycin for more severe infections. 1, 2
Oral Administration (Fosfomycin Tromethamine)
Preparation and Dosing
- Pour the entire contents of a single-dose 3g sachet into 3-4 ounces (1/2 cup) of cold or room temperature water and stir to dissolve 1
- Do not use hot water
- Take immediately after dissolving
- Can be taken with or without food, although food may slightly delay absorption 1, 2
Clinical Use
- Primarily used for uncomplicated urinary tract infections as a single 3g dose 1, 2
- Achieves high urinary concentrations (706 ± 466 mcg/mL) within 2-4 hours after administration under fasting conditions 1
- Maintains urinary concentrations above 100 mcg/mL for approximately 26 hours 2
- Bioavailability is approximately 37% under fasting conditions and 30% under fed conditions 2
Intravenous Administration
Clinical Use
- Used for more severe or complicated infections, including:
- Complicated urinary tract infections with or without bacteremia
- Infections caused by multidrug-resistant gram-negative bacteria 3
- Intravenous fosfomycin has been compared with piperacillin-tazobactam and meropenem in randomized controlled trials for complicated UTIs 3
- Provides high-certainty evidence for treatment of complicated UTIs with intravenous fosfomycin in patients without septic shock 3
Safety Considerations
- Monitor for heart failure, especially in at-risk patients (8.6% incidence reported in one trial) 3
- Reversible severe hypokalemia may occur during treatment 3
Pharmacokinetic Properties
- Half-life for elimination: 5.7 ± 2.8 hours 1, 2
- Approximately 38% of an oral dose is recovered in urine 1, 2
- Not bound to plasma proteins 1, 2
- Well-distributed to tissues including kidneys, bladder wall, prostate, and seminal vesicles 1, 2
- Renal impairment significantly decreases excretion and increases half-life (from 11 hours to 50 hours in severe impairment) 1, 2
Special Considerations
- In patients with renal insufficiency, the half-life is prolonged but no dosage adjustment is necessary for the single-dose treatment of uncomplicated UTIs 1, 2
- No dosage adjustment is necessary in elderly patients 1, 2
- For intravenous fosfomycin, susceptibility testing should be performed before treatment initiation 3
- Avoid use in patients with hypernatremia, cardiac or renal insufficiency when using intravenous formulation 3
Combination Therapy
- Fosfomycin may be used in combination with other antibiotics for synergistic effects against multidrug-resistant organisms 3, 4
- Common combination partners include tigecycline, polymyxin, and carbapenems 3
Fosfomycin's unique mechanism of action (inhibition of cell wall synthesis at an earlier step than β-lactams) makes it valuable for treating resistant infections, particularly when used appropriately according to its administration requirements 4, 5.