What is the recommended dose adjustment of Fosfomycin for patients with Acute Kidney Injury (AKI)?

Fosfomycin Dosing in Acute Kidney Injury

For patients with acute kidney injury (AKI), fosfomycin requires dose adjustment with a recommended loading dose of 8 g followed by a maintenance dose of 5 g after dialysis sessions in anuric patients, with therapeutic drug monitoring strongly recommended to ensure adequate serum levels. 1

Understanding Fosfomycin Pharmacokinetics in AKI

• Fosfomycin is a hydrophilic drug with negligible protein binding that is eliminated almost entirely by glomerular filtration, making it highly susceptible to changes in renal function 2
• In AKI, fosfomycin clearance is significantly reduced, potentially leading to drug accumulation and toxicity if doses are not appropriately adjusted 1
• Fosfomycin has a volume of distribution comparable to β-lactams and aminoglycosides, which may increase in critically ill patients, affecting drug concentrations 2

Dosing Recommendations for Fosfomycin in AKI

For Patients on Dialysis:

• A loading dose of 8 g is recommended, followed by a maintenance dose of 5 g after each dialysis session in anuric patients 1
• Standard loading doses of 5 g are insufficient to achieve serum levels above the EUCAST breakpoint (32 mg/L) for common bacteria in all patients undergoing dialysis 1
• Fosfomycin is rapidly eliminated during slow-extended daily dialysis (SLEDD), with clearance decreasing from 152 ± 10 mL/min at the start to 43 ± 38 mL/min at the end of dialysis sessions 1

For Non-Dialysis AKI Patients:

• Drug dosing should take GFR into account, as recommended by KDIGO guidelines for medication management in kidney disease 3
• Temporary discontinuation or dose adjustment of renally excreted drugs is recommended in patients with GFR < 60 ml/min/1.73 m² who have serious intercurrent illness that increases AKI risk 3
• Consider methods based on cystatin C or direct measurement of GFR when precision is required for dosing drugs with narrow therapeutic ranges 3

Monitoring and Safety Considerations

• Therapeutic drug monitoring is strongly recommended for fosfomycin in critically ill patients with AKI to ensure adequate dosing and avoid toxicity 1
• Fosfomycin serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI, making standardized dosing challenging 1
• For effective treatment, maintain fosfomycin levels above the minimum inhibitory concentration (MIC) for >70% of the dosing interval 1
• Consider that early renal dose adjustments may be premature in some patients, as AKI present on admission resolves within 48 hours in 57.2% of cases across various infection types 4

Clinical Considerations

• Assess the severity and cause of AKI before determining the appropriate fosfomycin dosing strategy 3
• Monitor for resolution of AKI, as unnecessary dose reductions in the setting of improving renal function may lead to reduced clinical response 4
• Consider that patients with cirrhosis and AKI may require special attention due to their altered pharmacokinetics and increased risk of hepatorenal syndrome 3
• Avoid potentially nephrotoxic agents when possible to prevent worsening of AKI 3

Pitfalls and Caveats

• Avoid premature dose reduction of fosfomycin in patients with AKI that may resolve quickly, as this could lead to subtherapeutic levels and treatment failure 4
• Be aware that standard dosing guidelines developed for chronic kidney disease may not be appropriate for the dynamic nature of AKI 4
• Remember that critically ill patients may experience augmented renal clearance despite AKI, potentially leading to subtherapeutic fosfomycin levels 2
• Consider that drug-induced AKI accounts for 19.3% of AKI cases, and proper dosing of medications like fosfomycin is crucial to prevent further kidney damage 5