Fosfomycin Use in UTI with CKD Stage 4
Fosfomycin can be used to treat urinary tract infections in patients with CKD stage 4, but dose adjustment and careful monitoring are necessary due to altered pharmacokinetics in renal impairment. 1, 2
Pharmacokinetics in Renal Impairment
- Fosfomycin is primarily eliminated by glomerular filtration, with approximately 38% of an oral dose recovered in urine 1
- In patients with varying degrees of renal impairment (creatinine clearances from 54 mL/min to 7 mL/min), the half-life of fosfomycin increases from 11 hours to 50 hours 1
- Despite reduced renal clearance, urinary concentrations of fosfomycin remain above 100 μg/mL regardless of the degree of renal insufficiency, which is therapeutically effective for most uropathogens 2
Dosing Recommendations for CKD Stage 4
- For oral fosfomycin in uncomplicated lower UTI with CKD stage 4, a single 3g dose may be sufficient due to prolonged urinary excretion in renal impairment 1, 2
- For complicated UTIs, consider extending the interval between doses rather than reducing the dose to maintain effective urinary concentrations 3
- For intravenous fosfomycin (where available), dose adjustment based on creatinine clearance is essential, with reduced dosing frequency recommended 4
Clinical Evidence and Considerations
- Fosfomycin has demonstrated effectiveness against multidrug-resistant organisms, including carbapenem-resistant Enterobacterales (CRE), making it valuable in the era of increasing antibiotic resistance 5
- In patients with severe renal dysfunction, therapeutic drug monitoring (TDM) should be performed when possible to ensure optimal dosing and avoid toxicity 5
- Fosfomycin has shown reasonable effectiveness as a last-resort oral treatment for lower UTI in special populations with impaired renal function, such as kidney transplant recipients 6
Safety Considerations
- The main concern in CKD stage 4 patients is the prolonged half-life of fosfomycin, which may lead to drug accumulation with repeated dosing 1, 3
- Despite this, historical evidence suggests fosfomycin has relatively low renal toxicity compared to other antibiotics used for resistant organisms 2
- Patients with hypernatremia or cardiac insufficiency in addition to renal insufficiency should avoid fosfomycin use due to potential exacerbation of these conditions 5
Treatment Approach for UTI in CKD Stage 4
- For uncomplicated lower UTI: Consider a single 3g oral dose of fosfomycin, with potential repeat dose after 48-72 hours if clinically indicated 1, 2
- For complicated UTI: Consider intravenous formulations (where available) with adjusted dosing based on creatinine clearance 4
- For UTIs caused by multidrug-resistant organisms: Fosfomycin may be used in combination with other antibiotics for synergistic effect, particularly for CRE infections 5
- Always confirm susceptibility through antimicrobial susceptibility testing before initiating treatment 5