What is the best treatment option for a 75-year-old patient with dementia and impaired renal function who has a urinary tract infection (UTI) sensitive only to Imipenem (Imipenem/Cilastatin)?

From the Guidelines

For a 75-year-old dementia patient with renal failure and a UTI sensitive only to imipenem, I strongly recommend treatment with imipenem-cilastatin, adjusted for renal function, as it is a carbapenem antibiotic effective against multidrug-resistant infections, as suggested by the European Society of Clinical Microbiology and Infectious Diseases guidelines 1.

Key Considerations

• The patient's renal function must be closely monitored, and the dose of imipenem-cilastatin should be adjusted accordingly to prevent toxicity, with a typical starting dose of 250-500 mg every 6 hours, reduced to 125-250 mg every 12 hours for severe renal impairment (creatinine clearance <30 mL/min) 1.
• Treatment duration should be 7-10 days for complicated UTI, and the patient should be watched for seizures, a potential side effect of imipenem, particularly in elderly patients with CNS disorders like dementia.
• Ensuring adequate hydration is crucial, and consulting with both infectious disease and nephrology specialists is recommended due to the complexity of managing this antibiotic in a patient with both dementia and renal failure.

Rationale

• Imipenem-cilastatin is effective against multidrug-resistant infections, making it an appropriate choice when sensitivity testing shows limited options, as supported by the guidelines for the treatment of infections caused by multidrug-resistant gram-negative bacilli 1.
• The cilastatin component prevents renal metabolism of imipenem, increasing its urinary concentration and effectiveness against UTI pathogens.
• Recent studies, such as those published in 2022, recommend imipenem-cilastatin as a treatment option for complicated UTIs caused by carbapenem-resistant Enterobacterales (CRE) 1.

From the FDA Drug Label

8.5 Geriatric Use Of the approximately 3,600 subjects ≥ 18 years of age in clinical studies of Imipenem and Cilastatin for Injection (I.V.), including postmarketing studies, approximately 2,800 received Imipenem and Cilastatin for Injection (I.V.) Of the subjects who received Imipenem and Cilastatin for Injection (I.V.), data are available on approximately 800 subjects who were 65 and over, including approximately 300 subjects who were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

1. 6 Renal Impairment Dosage adjustment is necessary in patients with renal impairment [see Dosage and Administration ( 2.3)] . Adult patients with creatinine clearances of less than or equal to 30 mL/min, whether or not undergoing hemodialysis, had a higher risk of seizure activity than those without impairment of renal function [see Warnings and Precautions ( 5. 2)] .

The patient is a 75-year-old with dementia and renal failure. Dosage adjustment is necessary in patients with renal impairment. The patient's renal function should be monitored, and care should be taken in dose selection due to the potential for toxic reactions in patients with impaired renal function 2. Seizure activity risk is higher in adult patients with creatinine clearances of less than or equal to 30 mL/min 2.

From the Research

Patient Considerations

• The patient is a 75-year-old with dementia and renal failure, which complicates the treatment of their UTI due to the potential for medication accumulation and toxicity 3.
• The patient's UTI is only sensitive to imipenem, a carbapenem antibiotic, which requires careful dosing in patients with renal impairment 4, 5.

Imipenem Dosing Considerations

• The total clearance of imipenem is reduced in patients with chronic renal failure, which may require dose adjustments to avoid toxicity 4.
• A study in patients with end-stage renal disease undergoing long-term hemodialysis found that a dose schedule of 500 mg every 12 hours was effective and maintained trough antibiotic activity 5.
• The Cockcroft-Gault equation should be used to adjust medicine doses, including imipenem, in patients with chronic renal impairment 3.

Treatment Decisions

• Treatment decisions for older adults with advanced chronic kidney disease should consider the patient's comorbidities, quality of life, and goals of care 6.
• The potential benefits and burdens of dialysis versus conservative management should be discussed with the patient and their family, taking into account the patient's unique situation and priorities 6.
• The high incidence of UTIs and associated mortality in people living with dementia highlights the need for prompt and effective treatment, while also considering the potential risks and benefits of treatment 7.