From the Guidelines
Fosfomycin can be used in patients with Chronic Kidney Disease (CKD) without dose adjustment, making it a convenient option for treating uncomplicated urinary tract infections in this population. The standard dose for adults is 3 grams as a single-dose sachet dissolved in water, which is typically sufficient even in patients with reduced kidney function 1. For uncomplicated cystitis, fosfomycin is recommended as a single dose, according to the American College of Physicians 1. Fosfomycin is primarily eliminated by the kidneys, but its unique pharmacokinetic profile allows for adequate urinary concentrations even in patients with impaired renal function. The medication achieves high concentrations in the urinary tract and maintains effectiveness against many uropathogens, including some multidrug-resistant organisms.
Key Considerations
- Patients should be advised to take fosfomycin on an empty stomach (2-3 hours after a meal) and to dissolve the powder completely in water before drinking.
- Common side effects include diarrhea, headache, and nausea, which are usually mild and transient.
- Fosfomycin's minimal systemic absorption and limited drug interactions make it particularly suitable for CKD patients who often take multiple medications.
Treatment Guidance
- For uncomplicated UTIs, a single dose of fosfomycin is recommended 1.
- For complicated UTIs in CKD patients, some clinicians may recommend a second 3-gram dose 48-72 hours after the first dose, though this is an off-label use.
Rationale
Urinary tract infections are among the most common bacterial infections requiring medical care, and fosfomycin is a viable treatment option for patients with CKD 1. The American College of Physicians recommends short-course antibiotics, including fosfomycin, for the treatment of uncomplicated cystitis and pyelonephritis 1.
From the FDA Drug Label
Renal Insufficiency: In 5 anuric patients undergoing hemodialysis, the t1/2 of fosfomycin during hemodialysis was 40 hours. In patients with varying degrees of renal impairment (creatinine clearances varying from 54 mL/min to 7 mL/min), the t1/2 of fosfomycin increased from 11 hours to 50 hours The percent of fosfomycin recovered in urine decreased from 32% to 11% indicating that renal impairment significantly decreases the excretion of fosfomycin.
Fosfomycin dosage adjustment is necessary in patients with Chronic Kidney Disease (CKD), as renal impairment significantly decreases the excretion of fosfomycin. The half-life of fosfomycin increases with decreasing renal function, ranging from 11 hours to 50 hours in patients with creatinine clearances varying from 54 mL/min to 7 mL/min. Key points to consider:
- Renal impairment: Decreases fosfomycin excretion
- Dosage adjustment: Necessary in patients with CKD
- Half-life: Increases with decreasing renal function 2
From the Research
Fosfomycin Use in CKD
- Fosfomycin is an antibiotic that can be used to treat urinary tract infections (UTIs) in patients with chronic kidney disease (CKD) 3, 4, 5.
- The daily dosage of fosfomycin may not need to be adjusted in patients with CKD, as it has been shown to be effective and safe in patients with renal insufficiency 3, 5.
- However, it is essential to consider the degree of renal insufficiency and the potential for accumulation of the drug in patients with severe CKD 6, 7.
Dosage Adjustment
- A study published in 1977 found that the urinary concentrations of fosfomycin were always higher than 100 μg/ml, regardless of the degree of renal insufficiency 3.
- Another study published in 2017 found that fosfomycin tromethamine was successful in treating cystitis in solid organ transplant recipients with renal dysfunction, with no significant difference in treatment success between patients with creatinine clearance <40 mL/min and those with creatinine clearance ≥40 mL/min 5.
Safety and Efficacy
- Fosfomycin has been shown to be effective and safe in patients with CKD, with a low risk of nephrotoxicity and systemic toxicity 3, 5.
- However, it is crucial to monitor patients with CKD closely for signs of adverse effects and to adjust the dosage accordingly 6, 7.
- A study published in 2019 found that fosfomycin-trometamol had a reasonable effectiveness as a last-resort oral treatment for lower UTI and stepdown treatment for upper UTI in kidney transplant recipients 4.
Special Considerations
- Patients with CKD are at a higher risk of developing UTIs and sepsis due to metabolic disturbances, chronic inflammation, and impaired immunocompetence 7.
- The diagnosis of UTI in CKD is based on standard clinical and laboratory criteria, but pyuria may be more often observed in patients with oligoanuria and low bacterial colony counts 7.
- Treatment strategies for UTI in CKD are based on the same principles as in patients with normal renal function, but drugs cleared by the kidney or by dialysis membranes need dose adjustment 6, 7.