Fosfomycin: drug profile

Mechanism of action

• Enters bacteria through glycerophosphate and glucose-6-phosphate transport systems.
• Irreversibly inhibits MurA (UDP-N-acetylglucosamine enolpyruvyl transferase), an early enzyme in peptidoglycan cell-wall synthesis.
• This distinct target means cross-resistance with most other antibacterial classes is uncommon.
• It is bactericidal. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, p. 1174.

Antibacterial spectrum

• Often active: E. coli, Enterococcus spp., Proteus spp., and Staphylococcus saprophyticus.
• Activity can be variable: Klebsiella, Enterobacter, Serratia.
• Susceptibility testing and local resistance data matter, particularly for multidrug-resistant Gram-negative organisms.
• Pseudomonas aeruginosa and Acinetobacter have unreliable or poor susceptibility in routine oral-UTI use. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, p. 1174.
• Oral fosfomycin can retain activity against many ESBL-producing urinary Enterobacterales, but it should not be used indiscriminately for resistant organisms or systemic infection.

Pharmacokinetics

• Oral bioavailability: about 40%.
• Half-life: approximately 5-8 hours.
• Oral 3-g dose produces low serum concentrations but very high urinary concentrations, roughly 1000-4000 micrograms/mL, maintained for up to about 48 hours.
• Excreted largely unchanged in urine.
• Reduced renal function prolongs the half-life and reduces urinary excretion. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, p. 1174.

Adverse effects

• Diarrhea
• Nausea, dyspepsia, abdominal upset
• Headache
• Dizziness
• Vaginitis/vulvovaginal symptoms

• Hypersensitivity reactions
• Antibiotic-associated diarrhea, including Clostridioides difficile infection. Persistent or severe diarrhea after treatment needs medical assessment. DailyMed warning

Contraindication and precautions

• Contraindicated: known hypersensitivity to fosfomycin.
• Do not rely on oral fosfomycin for fever, flank pain, sepsis, suspected pyelonephritis, renal/perinephric abscess, prostatitis, or bacteremia, because blood and renal-tissue concentrations are inadequate.
• Obtain urine culture and susceptibility testing in recurrent, complicated, resistant, or treatment-failure cases.
• Avoid routine repeat or prophylactic dosing unless directed by a clinician. Multi-dose regimens are used off label in selected situations, but are not the standard licensed single-dose regimen.

Interactions

• Metoclopramide and other agents that increase gastrointestinal motility can lower fosfomycin serum and urinary concentrations, potentially reducing efficacy.
• Cimetidine has no clinically meaningful effect on its pharmacokinetics. DailyMed interactions

Pregnancy and breastfeeding

• Fosfomycin is commonly considered an option for lower UTI in pregnancy when clinically indicated and guided by culture/local policy. Treatment of asymptomatic bacteriuria or symptomatic UTI during pregnancy should be supervised by an obstetric clinician.
• Check current local guidance for use while breastfeeding and in children, since recommendations vary by formulation and country.

Practical counseling points

1. Dissolve the entire 3-g sachet in water. Do not take the dry granules directly.
2. It treats bladder infection, not kidney infection.
3. Symptoms should begin improving within a few days. Seek care promptly for fever, chills, vomiting, flank pain, worsening symptoms, or no improvement.
4. Do not reuse leftover sachets for future urinary symptoms.