fosfomycin
phosphonic acid antibiotic· Brands: Monuril, Monurol, Fosfocin, Uro-FosfomycinIVPO
Mechanism of action
Fosfomycin is a phosphonic acid derivative that inhibits bacterial cell wall synthesis by inactivating the enzyme pyruvyl transferase (UDP-N-acetylglucosamine enolpyruvyl transferase, MurA), which catalyses an early step in peptidoglycan synthesis. This action disrupts the formation of the bacterial cell wall, leading to cell lysis. It is a bactericidal antibiotic with activity against a range of Gram-positive and Gram-negative bacteria, including many strains that are resistant to other agents.
Pharmacokinetics
Fosfomycin is absorbed from the gastrointestinal tract after oral administration, with a bioavailability of approximately 30 to 40%. Peak plasma concentrations occur 2 to 4 hours after dosing. It is not significantly bound to plasma proteins and distributes widely throughout the body, including the urinary tract. The drug is not metabolised to a significant extent and is excreted unchanged in the urine, mainly by glomerular filtration, with a terminal half-life of about 3 to 5 hours. Following intravenous administration, higher plasma concentrations are achieved, but elimination remains predominantly renal.
Indications & dosing
Acute uncomplicated cystitis in adult women
Standard single dose; administer with water, preferably on an empty stomach.
- adult · PO: 3 g single dose · Standard single dose; administer with water, preferably on an empty stomach.
Asymptomatic bacteriuria in pregnancyoff-label
Used as an alternative when other oral antibiotics are not suitable; seek specialist advice.
- adult · PO: 3 g single dose · Used as an alternative when other oral antibiotics are not suitable; seek specialist advice.
Chronic bacterial prostatitisoff-label
Duration typically 7-14 days; not licensed for this indication.
- adult · PO: 3 g every 48-72 hours · Duration typically 7-14 days; not licensed for this indication.
Contraindications & precautions
- Hypersensitivity to fosfomycin or any component of the formulation · Cross-reactivity with other agents is not well defined; avoid in patients with a history of immediate-type allergic reactions to fosfomycin.
- Severe renal impairment (creatinine clearance < 30 ml/min) for oral formulation · Oral fosfomycin is not recommended for the treatment of uncomplicated lower urinary tract infections in patients with severe renal impairment due to reduced efficacy.
- Children under 12 years for oral formulation · Not licensed for use in children under 12 years; safety and efficacy not established.
- Administer oral fosfomycin on an empty stomach, at least 2 to 3 hours after food, to ensure optimal absorption.
- Monitor serum potassium levels when using IV fosfomycin, particularly in patients on diuretics or with cardiac disease, as hypokalemia may occur.
- Use caution in patients with a history of epilepsy or seizure disorders, especially with high-dose IV fosfomycin, as it may lower the seizure threshold.
- Fosfomycin is not appropriate for the treatment of pyelonephritis, complicated urinary tract infections, or infections outside the urinary tract; reserve for acute uncomplicated cystitis.
- Consider alternative therapy in patients with severe renal impairment (creatinine clearance < 30 ml/min) when using the oral formulation.
Adverse effects
- Diarrhoea
- Nausea
- Headache
- Dizziness
- Hypersensitivity reactions including urticaria, angioedema, and anaphylaxisserious
- Clostridium difficile-associated diarrhoeaserious
Renal & hepatic adjustment
- eGFR 60–300: No dose adjustment required for either oral or intravenous forms.
- eGFR 30–59: Oral: no adjustment required. Intravenous: increase dosing interval or reduce total daily dose.
- eGFR 0–29: Oral: avoid due to reduced urine concentrations. Intravenous: reduce dose and use with caution; monitor renal function and electrolytes.
Monitoring, pregnancy & toxicity
- Serum creatinine (eGFR) · Baseline and periodically during intravenous therapy
- Serum electrolytes · Baseline and during therapy, especially if intravenous
- Blood pressure · During intravenous infusion
- Pregnancy: Fosfomycin may be used during pregnancy when indicated, particularly for urinary tract infections. It is not known to cause harm, although data are limited; alternative antibiotics may be preferred in early pregnancy or when other options are suitable.
- Toxicity: Gastrointestinal disturbances: diarrhoea, nausea, vomiting. · Supportive care; maintain hydration and monitor electrolytes if severe.
- Toxicity: Hypersensitivity reactions: rash, pruritus, angioedema, or anaphylaxis. · Discontinue the drug; treat with antihistamines, corticosteroids, or epinephrine as needed for anaphylaxis.
- Toxicity: Overdose: no specific antidote; symptoms are usually gastrointestinal. · Provide supportive care; monitor renal function and electrolytes, particularly if the intravenous form has been given.
Clinical notes
Fosfomycin is indicated for the treatment of uncomplicated lower urinary tract infections (acute cystitis) in women, caused by susceptible organisms such as Escherichia coli and Enterococcus faecalis. It is usually given as a single oral dose of 3 g, dissolved in water. In some settings, it is also available intravenously for serious systemic infections due to susceptible Gram-positive or Gram-negative bacteria. Antimicrobial susceptibility testing is recommended to guide therapy. The drug should be avoided in patients with severe renal impairment (creatinine clearance below 10 ml/min) and used with caution in those with mild to moderate renal dysfunction. Fosfomycin is generally well tolerated, with gastrointestinal effects being the most common adverse reactions.
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BNF; local formulary