What is the typical dose of Inj (Intravenous) Fosfomycin for a patient with a bacterial infection and potentially Impaired renal function?

Intravenous Fosfomycin Dosing

For bacterial infections in patients 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 Regimens

Normal Renal Function

• The recommended dose is 12-24 g/day divided into 3 or 4 doses 1
• Common regimens include:
  • 4 g every 6 hours (16 g/day) 2, 3
  • 6 g every 6 hours (24 g/day) 2
  • 8 g every 8 hours (24 g/day) 4, 2
• A loading dose of 8 g followed by continuous infusion of 16-24 g/day may optimize pharmacodynamic targets 4

Administration Method

• Prolonged or continuous infusion is preferred over intermittent bolus dosing to maximize time-dependent killing characteristics 4, 2
• Standard infusions are given over 30 minutes to 4 hours 1, 2
• Continuous 24-hour infusion after a loading dose shows promise for optimizing drug exposure 4

Renal Impairment Considerations

Fosfomycin is eliminated almost exclusively by glomerular filtration, requiring dose adjustment in renal dysfunction 5, 6

• The elimination half-life increases dramatically with renal impairment: from 11 hours (CrCl 54 mL/min) to 50 hours (CrCl 7 mL/min) 5
• In anuric patients on hemodialysis, the half-life extends to 40 hours 5
• Fosfomycin is 70-80% dialyzable during hemodialysis sessions 7
• Dose after dialysis to facilitate directly observed therapy and avoid premature drug removal 1

Critical caveat: Specific dosing regimens for various degrees of renal impairment remain inadequately studied and require further investigation 4. Monitor renal function closely and consider therapeutic drug monitoring when available.

Mandatory Combination Therapy

Fosfomycin must always be administered in combination with another active antimicrobial agent 1

• Monotherapy leads to rapid emergence of resistant bacterial strains 4, 2
• This is particularly critical for Pseudomonas aeruginosa infections, where fosfomycin monotherapy fails to achieve pharmacodynamic targets even at high doses 2
• The combination partner should be selected based on susceptibility testing results 1

Pharmacodynamic Targets

For optimal efficacy, fosfomycin dosing should achieve:

• Time above MIC (%T>MIC) > 70% for all pathogens 2
• AUC24/MIC > 24 for Enterobacterales 2
• AUC24/MIC > 15 for Pseudomonas aeruginosa 2

MIC-Based Dosing Guidance

• For MIC ≤ 32 mg/L (EUCAST breakpoint for Enterobacterales): 4 g every 8 hours or higher achieves >90% probability of target attainment 2
• For MIC = 64 mg/L: requires 6 g every 6 hours or 8 g every 8 hours 2
• For P. aeruginosa with MIC 256-512 mg/L: no monotherapy regimen achieves adequate targets; combination therapy is essential 2

Special Populations

Critically Ill Patients

• Volume of distribution is increased in critically ill patients with bacterial infections compared to healthy volunteers 2
• This may necessitate higher doses or loading dose strategies 4
• Fosfomycin concentrations are highly variable in this population 3

Non-Critically Ill Patients with Bacteremic UTI

• 4 g every 6 hours is effective for bacteremic urinary tract infections caused by multidrug-resistant E. coli 3
• Higher doses may increase toxicity without significantly improving efficacy in this population 3

Common Pitfalls

• Avoid monotherapy: This is the most critical error, leading to rapid resistance development 4, 2
• Do not use standard doses in renal impairment without adjustment, as drug accumulation and toxicity will occur 5, 6
• Avoid intermittent bolus dosing when prolonged or continuous infusion is feasible, as this optimizes time-dependent killing 4
• Do not assume CLSI breakpoints are adequate: Current evidence suggests fosfomycin susceptibility breakpoints may need reappraisal 3