Usage
Fosfomycin is a broad-spectrum antibiotic prescribed for the treatment of acute, uncomplicated lower urinary tract infections (UTIs), particularly acute cystitis, caused by susceptible strains of bacteria like Escherichia coli and Enterococcus faecalis. It is also effective against some multi-drug resistant bacteria. Although not typically a first-line treatment, it serves as a valuable alternative when other commonly used antibiotics are contraindicated or ineffective. It is not indicated for pyelonephritis or perinephric abscess. Its pharmacological classification is antibiotic.
Fosfomycin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It achieves this by irreversibly blocking the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, which is crucial in the early stages of peptidoglycan synthesis. This inhibition prevents the formation of UDP-N-acetylmuramyl-pentapeptide, a key building block of the bacterial cell wall, ultimately leading to bacterial cell death.
Alternate Names
Fosfomycin tromethamine (oral formulation)
Fosfomycin disodium (intravenous formulation)
Monurol (brand name)
How It Works
Pharmacodynamics: Fosfomycin primarily targets the bacterial cell wall, disrupting its synthesis and leading to cell death. It demonstrates activity against a broad range of gram-negative and gram-positive bacteria. It is not effective against anaerobic bacteria.
Pharmacokinetics:
- Absorption: The oral formulation (fosfomycin tromethamine) is absorbed relatively well, reaching peak plasma concentrations within 2-4 hours. Food can delay but does not significantly reduce absorption. The intravenous formulation (fosfomycin disodium) provides direct systemic exposure.
- Distribution: Fosfomycin distributes widely into various tissues and fluids, including the kidneys, bladder, and urine, where it achieves high concentrations, crucial for treating UTIs. It also penetrates into bone tissue.
- Metabolism: Fosfomycin is not metabolized in the liver. This property is beneficial for patients with hepatic impairment, as no dosage adjustment is typically required.
- Elimination: The drug is primarily eliminated unchanged through the kidneys via glomerular filtration. Consequently, patients with renal impairment may require dosage adjustments. A small amount is also excreted in breast milk.
Mode of Action: Fosfomycin acts as a phosphoenolpyruvate analog and irreversibly inhibits UDP-N-acetylglucosamine enolpyruvyl transferase, a bacterial enzyme essential for cell wall synthesis. This inhibition disrupts the formation of peptidoglycan polymers, compromising the structural integrity of the bacterial cell wall, which ultimately leads to cell lysis and death. The drug does not bind to bacterial ribosomes or interfere with protein synthesis.
Dosage
Standard Dosage
Adults: For acute uncomplicated cystitis: A single oral dose of 3 g of fosfomycin tromethamine dissolved in 90-120 mL of water. For multi-drug resistant UTIs: 2-3 g orally every 2-3 days for 3 doses.
Children: Dosing is based on weight and age. Consult a specialist for specific recommendations. Oral use in neonates is not routine.
Special Cases:
- Elderly Patients: No dose adjustments are needed for elderly patients solely due to age. However, renal function should be evaluated.
- Patients with Renal Impairment: Dosage adjustment is needed for patients with renal insufficiency. Consult dosing guidelines for creatinine clearance thresholds.
- Patients with Hepatic Dysfunction: No dosage adjustment is typically required due to lack of liver metabolism.
- Patients with Comorbid Conditions: Careful monitoring is essential for patients with other underlying medical conditions. Individualized adjustments might be needed on a case-by-case basis.
Clinical Use Cases
For specific clinical use cases (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations), dosage information is limited in the provided sources. Please consult specific guidelines or specialists for such cases.
Dosage Adjustments
Dosage adjustments are primarily based on renal function, with specific dosage recommendations for varying degrees of creatinine clearance (e.g., <10 mL/min, 10-20 mL/min, 20-30 mL/min, 30-40 mL/min).
Side Effects
Common Side Effects
Diarrhea, nausea, headache, dizziness, vaginitis, vaginal itching or discharge, back pain, asthenia (weakness), sore throat, runny nose, abdominal pain, dyspepsia.
Rare but Serious Side Effects
Severe diarrhea, Clostridium difficile-associated colitis, vision changes, allergic reactions (including hives, difficulty breathing, swelling of the face, lips, tongue, or throat).
Long-Term Effects
No specific long-term effects are noted in the provided sources. However, any antibiotic use can potentially lead to issues like antimicrobial resistance with prolonged use.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate attention include angioedema, severe allergic reactions, pseudomembranous colitis, and significant changes in vision.
Contraindications
Known hypersensitivity to fosfomycin. Severe renal failure (creatinine clearance < 10 mL/min) for the oral formulation. The use of fosfomycin in patients undergoing hemodialysis is generally avoided.
Drug Interactions
Metoclopramide, cisapride, various vitamins, live bacterial vaccines (cholera, typhoid, BCG). The interaction with metoclopramide may lead to decreased effectiveness of fosfomycin. Concurrent use with other medications, including antacids containing metal cations (e.g., aluminum, magnesium), should be avoided as they can reduce fosfomycin absorption. Probenecid can increase serum fosfomycin concentrations, potentially increasing the risk of adverse effects.
Pregnancy and Breastfeeding
Fosfomycin is generally considered safe for use during pregnancy, especially for UTIs, when the benefits outweigh potential risks. It is classified as Pregnancy Category B. The drug is excreted in breast milk in small amounts. Caution is advised during breastfeeding, but it is generally considered compatible with breastfeeding. Consult guidelines for further information.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by blocking UDP-N-acetylglucosamine enolpyruvyl transferase.
- Side Effects: Common: Diarrhea, nausea, headache. Serious: C. difficile colitis, allergic reactions.
- Contraindications: Hypersensitivity to fosfomycin; severe renal failure (oral formulation).
- Drug Interactions: Metoclopramide, cisapride, live vaccines.
- Pregnancy & Breastfeeding: Generally considered safe. Caution advised.
- Dosage: Adults: 3 g PO once for uncomplicated UTI. Pediatric: Consult guidelines.
- Monitoring Parameters: Urine culture, renal function tests.
Popular Combinations
No specific drug combinations are mentioned in the provided sources for routine usage with fosfomycin. Combination therapy is generally not recommended for uncomplicated UTIs. For complicated infections, other antibiotics might be combined depending on the identified pathogen and resistance profile.
Precautions
Assess renal function before initiating therapy, especially in elderly patients. Monitor for allergic reactions and gastrointestinal disturbances. Caution advised for patients with a history of colitis. Avoid concurrent use of antacids.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fosfomycin?
A: For adults with uncomplicated UTIs: 3 g of fosfomycin tromethamine orally as a single dose. Pediatric and other dosages require specialist advice.
Q2: How does Fosfomycin work?
A: Fosfomycin inhibits bacterial cell wall synthesis by irreversibly blocking UDP-N-acetylglucosamine enolpyruvyl transferase.
Q3: What are the common side effects of Fosfomycin?
A: Common side effects include diarrhea, nausea, headache, dizziness, and vaginitis.
Q4: Can Fosfomycin be used during pregnancy?
A: Yes, fosfomycin is generally considered safe for use during pregnancy when benefits outweigh risks. It’s categorized as Pregnancy Category B. However, inform your healthcare provider.
Q5: Are there any contraindications to Fosfomycin?
A: Yes, contraindications include known hypersensitivity to fosfomycin and severe renal failure (especially for the oral formulation).
Q6: How is Fosfomycin excreted?
A: Fosfomycin is primarily eliminated unchanged by the kidneys. Dosage adjustments are needed for patients with impaired renal function.
Q7: What is the advantage of using Fosfomycin for UTIs?
A: Its single-dose regimen for uncomplicated UTIs offers good patient compliance, and it’s effective against some multidrug-resistant bacteria.
Q8: Does Fosfomycin interact with other medications?
A: Yes, it can interact with certain drugs like metoclopramide. Concomitant administration may reduce fosfomycin effectiveness. It also interacts with live bacterial vaccines and antacids.
Q9: Can Fosfomycin be used to treat pyelonephritis?
A: No, fosfomycin is not recommended for pyelonephritis as adequate drug levels in the kidneys might not be achievable with oral administration.
Q10: What is the difference between fosfomycin tromethamine and fosfomycin disodium?
A: Fosfomycin tromethamine is administered orally, while fosfomycin disodium is for intravenous administration. Both have similar activity against susceptible organisms, but they are used in different clinical situations.
