Fosfomycin Dosing in Dialysis Patients
For patients on hemodialysis, administer fosfomycin 2 grams intravenously after each dialysis session (3 times weekly), as fosfomycin is actively eliminated by the dialyzer and requires post-dialysis replacement dosing.
Pharmacokinetic Rationale in Dialysis
Fosfomycin is significantly removed by hemodialysis, with clearance by the dialyzer reaching 103 ± 10 mL/min and 70-80% of the drug being dialyzed through artificial kidney membranes 1, 2.
The elimination half-life is dramatically prolonged in anuric patients from 5.7 hours in normal renal function to 40-50 hours between dialysis sessions 3, 1.
Fosfomycin clearance during dialysis decreases progressively from 152 ± 10 mL/min at the start of a SLEDD session to 43 ± 38 mL/min at the end, indicating time-dependent elimination 4.
Specific Dosing Recommendations
Standard Hemodialysis Protocol
Administer 2 grams IV immediately after each hemodialysis session to prevent premature drug removal and maintain therapeutic levels between sessions 1, 2.
Post-dialysis administration timing is critical because giving fosfomycin before dialysis results in rapid elimination with a half-life of only 4.2 hours, versus 48.8 hours when given after dialysis 1.
This approach follows the general principle that medications for dialysis patients should be administered after the dialysis session to prevent premature removal and facilitate directly observed therapy 5.
Intensive Care/Severe Infections
For critically ill septic patients on SLEDD requiring higher doses, consider a loading dose of 8 grams followed by 5 grams after each dialysis session 4.
A standard loading dose of 5 grams may be insufficient to achieve serum levels above the EUCAST breakpoint of 32 mg/L for common pathogens in all patients, particularly when targeting T > MIC > 70% of the dosing interval 4.
Therapeutic drug monitoring is strongly recommended in critically ill patients with AKI undergoing dialysis therapy due to wide variability in serum concentrations 4.
Monitoring Requirements
Baseline renal function assessment with serum creatinine and eGFR calculation is essential before initiating therapy 5.
Monitor creatinine every 3-7 days during treatment, as fosfomycin accumulation could theoretically worsen renal function, though this is less concerning in anuric dialysis patients 5.
Serum fosfomycin levels should be monitored in critically ill patients to ensure adequate drug absorption without excessive accumulation and to avoid toxicity 4.
Clinical Efficacy Considerations
Urinary concentrations remain therapeutic even in patients with impaired renal function, with levels of 1,383 mg/L in the first 12 hours declining to 165 mg/L between 36-48 hours, exceeding MIC for usual pathogens for at least 48 hours 6.
Approximately 37% of the oral dose is recovered unchanged in urine after 84 hours in patients with renal impairment (mean creatinine clearance 40 mL/min), though wide variability exists (15-60%) 6.
For systemic infections requiring higher doses, the standard recommendation is 12-24 grams/day in 3-4 divided doses, always in combination therapy 7.
Critical Pitfalls to Avoid
Never administer fosfomycin immediately before dialysis, as this results in 70-80% drug removal and subtherapeutic levels 2.
Do not use standard dosing intervals (every 6-8 hours) in dialysis patients, as the prolonged half-life of 40-50 hours between sessions makes this unnecessary and potentially toxic 1.
Avoid relying solely on standard loading doses in septic patients, as 3/5 patients receiving 5 grams fell below therapeutic breakpoints after 4-6 hours of SLEDD 4.