What is the recommended intravenous fosfomycin dosing regimen for severe adult infections, and how should the dose be adjusted in patients with impaired renal function?

Intravenous Fosfomycin Dosing for Severe Adult Infections

For severe adult infections with normal renal function, administer intravenous fosfomycin 12-24 g/day divided into 3-4 doses (typically 4-8 g every 6-8 hours), always in combination with another active antimicrobial agent. 1

Standard Dosing Regimen

• The recommended dose is 12-24 g/day divided into 3-4 doses for patients with normal renal function 1
• A loading dose of 8 g followed by 16-24 g/day via continuous infusion represents an optimal approach based on pharmacokinetic/pharmacodynamic modeling 2
• For complicated upper urinary tract infections specifically, 6 g every 8 hours (18 g/day total) for 7 days has demonstrated efficacy in clinical trials 3
• Fosfomycin must never be used as monotherapy—combination with another active antimicrobial is mandatory to prevent emergence of resistance 1, 4

Renal Dose Adjustment

Fosfomycin is eliminated almost exclusively by glomerular filtration and requires dose adjustment in renal impairment 1, 5:

• For severe renal insufficiency, reduce the dosing frequency to 2-3 times weekly while maintaining the individual dose at 12-15 mg/kg per dose 6
• Do not reduce the milligram amount per dose, as this compromises the concentration-dependent bactericidal effect—instead, extend the interval between doses 6
• Serum drug concentrations should be monitored in patients with severe renal impairment to avoid toxicity 6
• For hemodialysis patients, administer the dose after dialysis to avoid premature drug removal 6

Critical Implementation Considerations

Before initiating therapy:

• Confirm pathogen susceptibility to fosfomycin through antimicrobial susceptibility testing, or document synergistic activity with the combination partner 4
• Select the combination antimicrobial based on susceptibility results 1

Contraindications and precautions:

• Avoid fosfomycin in patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency without dose adjustment 4
• The main adverse reaction is reversible severe hypokalemia, which occurred in 3 of 48 ICU patients in one observational study 4

Infusion Strategy

• Prolonged or continuous infusion may be superior to intermittent bolus dosing based on time-dependent pharmacodynamics, though clinical superiority requires further validation 2
• When using intermittent dosing, infuse each dose over 30 minutes to several hours depending on the total dose 5
• For critically ill patients, consider an 8 g loading dose followed by continuous infusion of 16-24 g/day to optimize pharmacokinetic/pharmacodynamic targets 2

Common Pitfalls to Avoid

• Never use fosfomycin as monotherapy—resistance emerges rapidly without a combination partner 1, 4
• Do not reduce the individual dose amount in renal impairment; instead extend the dosing interval 6
• Do not skip susceptibility testing or synergy testing before initiating therapy 4
• Avoid in patients with cardiac or renal insufficiency without appropriate dose modification and monitoring 4

Evidence Quality Note

The evidence supporting fosfomycin use for carbapenem-resistant Enterobacterales infections is of very low quality, with observational studies showing a trend toward reduced mortality (RR 0.55,95% CI 0.28-1.10) when used in combination therapy 4. Treatment efficacy in ICU patients was 54.2% with a 28-day mortality of 37.5% 4. Despite limited evidence quality, fosfomycin represents a valuable option for multidrug-resistant infections when used appropriately in combination therapy 4, 1.