What is the recommended dose of intravenous (IV) fosfomycin for treating systemic infections?

Recommended Dosing of Intravenous Fosfomycin for Systemic Infections

The recommended dose of intravenous fosfomycin for treating systemic infections in adults is 16-24 g/day divided in 3-4 doses (e.g., 6-8 g every 8 hours), with an initial loading dose of 8 g. 1

Dosing Recommendations Based on Infection Type

For Carbapenem-Resistant Enterobacterales (CRE) Infections:

• Loading dose: 8 g IV
• Maintenance dose: 6-8 g IV every 8 hours (16-24 g/day)
• Administration: Preferably as prolonged (3-4 hour) or continuous infusion 2, 1

For Carbapenem-Resistant Acinetobacter baumannii:

• Dose: 12-24 g/day in 3-4 divided doses
• Note: Always use in combination therapy with another active antimicrobial to prevent resistance development 2, 1

For Vancomycin-Resistant Enterococci (VRE):

• For systemic infections: Same as above (16-24 g/day)
• For uncomplicated urinary tract infections: 3 g PO as a single dose 2

Dosing in Special Populations

Pediatric Patients:

• Neonates: No specific IV dosing recommendations available
• Children <12 years: 2000 mg/dose PO as a single dose (for UTI only)
• Children ≥12 years: 3000 mg/dose PO as a single dose (for UTI only) 2

Renal Impairment:

• Dose adjustment required based on creatinine clearance
• Consider therapeutic drug monitoring when available 2

Administration Considerations

1. Infusion Method: Prolonged infusion (3-4 hours) or continuous infusion provides better pharmacodynamic target attainment than intermittent infusion 1

2. Combination Therapy: Always use in combination with another active antimicrobial agent to prevent the emergence of resistance 1, 3

3. Duration of Therapy: Based on infection site, source control, underlying comorbidities, and initial response to therapy 2

Pharmacokinetic/Pharmacodynamic Considerations

• Fosfomycin is a time-dependent antibiotic
• Target PK/PD parameter: Time above MIC (T>MIC)
• For optimal efficacy, maintain plasma concentrations above the MIC for at least 40-70% of the dosing interval 4
• Continuous or prolonged infusion helps achieve this target 1

Monitoring

• Monitor renal function regularly
• Consider therapeutic drug monitoring when available
• Watch for hypokalemia, which can occur with high-dose IV fosfomycin 2

Clinical Pearls and Caveats

1. Resistance Development: Monotherapy with fosfomycin should be avoided due to rapid development of resistance 1, 5

2. Synergistic Effects: Fosfomycin demonstrates synergistic effects when combined with other antibiotics, particularly against multidrug-resistant organisms 5

3. Tissue Penetration: Fosfomycin has excellent tissue penetration, making it suitable for infections of the CNS, soft tissues, bone, lungs, and abscesses 5

4. Bioavailability: Oral fosfomycin has <50% bioavailability, limiting its use to uncomplicated UTIs when administered orally 5

5. Emerging Evidence: Higher dosing regimens (up to 24 g/day) may be needed for infections caused by organisms with higher MICs (≥32 mg/L) 6, 4

The dosing recommendations provided are based on the most recent guidelines and evidence. However, local antimicrobial stewardship programs and infectious disease consultation should be considered for complex cases involving multidrug-resistant organisms.