What are the considerations for using Fosfomycin (an antibiotic) in the elderly population with potential Impaired renal function?

From the Guidelines

Fosfomycin is a suitable antibiotic option for treating urinary tract infections (UTIs) in older adults, including those with potential impaired renal function, due to its minimal drug interactions and favorable safety profile. The standard dose is 3 grams of fosfomycin tromethamine powder dissolved in water, taken as a single dose 1. For older patients with uncomplicated cystitis, this one-time treatment is typically sufficient. Fosfomycin is particularly valuable for older patients because it has good tissue penetration and maintains efficacy against many multi-drug resistant organisms, including ESBL-producing bacteria. It also has a favorable safety profile with few adverse effects, mainly mild gastrointestinal disturbances like diarrhea or nausea in about 10% of patients.

When considering the use of fosfomycin in older adults with impaired renal function, it is essential to note that the drug is primarily excreted unchanged in the urine, which contributes to its effectiveness in treating UTIs. However, fosfomycin should be used cautiously in patients with severe renal impairment (CrCl <10 mL/min), as its efficacy and safety in this population are not well established 1. In patients with reduced renal function, careful consideration of potential drug interactions and contraindications, such as impaired kidney function, is necessary to optimize outcomes in this vulnerable population 1.

Key considerations for using fosfomycin in older adults with potential impaired renal function include:

• Minimal drug interactions
• Favorable safety profile
• Efficacy against multi-drug resistant organisms
• Primary excretion unchanged in the urine
• Caution in patients with severe renal impairment (CrCl <10 mL/min)
• Careful consideration of potential drug interactions and contraindications in patients with reduced renal function.

From the FDA Drug Label

Special Populations Geriatric: Based on limited data regarding 24-hour urinary drug concentrations, no differences in urinary excretion of fosfomycin have been observed in elderly subjects. No dosage adjustment is necessary in the elderly. 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.

The key considerations for using Fosfomycin in the elderly population with potential impaired renal function are:

• No dosage adjustment is necessary in the elderly based on limited data.
• Renal impairment significantly decreases the excretion of fosfomycin, with the half-life increasing from 11 hours to 50 hours in patients with varying degrees of renal impairment.
• Caution should be exercised when using fosfomycin in patients with impaired renal function, as the decreased excretion may lead to increased drug concentrations and potential adverse effects 2.

From the Research

Considerations for Using Fosfomycin in the Elderly Population

Impaired Renal Function

• Fosfomycin is an antibiotic that has been found to be effective in treating urinary tract infections (UTIs), including those caused by multidrug-resistant microorganisms 3, 4.
• However, its use in the elderly population with impaired renal function requires careful consideration, as the drug's efficacy and safety may be affected by reduced kidney function.
• A study on nitrofurantoin, another antibiotic used to treat UTIs, found that mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of the drug 5.
• However, there is limited information available on the specific use of fosfomycin in elderly patients with impaired renal function, and more studies are needed to confirm its safety and efficacy in this population 3, 4.

Dosage and Administration

• The dosage and administration of fosfomycin may need to be adjusted in elderly patients with impaired renal function to minimize the risk of adverse effects 4.
• A study on the use of oral fosfomycin in patients with complicated lower urinary tract infections found that a regimen of 3 grams administered once every 48 or 72 hours for a total of 3 doses was effective 4.
• However, the optimal dosage and administration schedule for fosfomycin in elderly patients with impaired renal function have not been established, and further research is needed to determine the best approach 3, 4.

Monitoring and Adverse Effects

• Elderly patients with impaired renal function who are treated with fosfomycin should be closely monitored for adverse effects, such as changes in kidney function or the development of resistant microorganisms 3, 4.
• A study comparing fosfomycin to nitrofurantoin for the treatment of uncomplicated lower urinary tract infections found that treatment failure was more common in the fosfomycin group, although reinfection rates were higher among patients who received nitrofurantoin 6.
• The incidence of adverse events was found to be more in fosfomycin relative to the nitrofurantoin group in another study 7.