Should an elderly patient with impaired renal function, being treated with intravenous (IV) ceftriaxone (Ceftriaxone) for a urinary tract infection (UTI) caused by pan-sensitive Escherichia coli (E. coli), be stepped down to oral amoxicillin or trimethoprim/sulfamethoxazole (Septra)?

From the Guidelines

For this elderly patient with a UTI caused by pan-sensitive E. coli, I strongly recommend stepping down to oral amoxicillin-clavulanate (Augmentin) rather than amoxicillin alone or trimethoprim-sulfamethoxazole (Septra). A typical regimen would be amoxicillin-clavulanate 875/125 mg twice daily for a total of 7 days of antibiotic therapy (including the days already on IV ceftriaxone) 1. Given her moderate renal impairment with GFR of 45 and creatinine of 95, no dose adjustment is needed for amoxicillin-clavulanate at this level of kidney function.

Key Considerations

• Amoxicillin-clavulanate provides better coverage against E. coli than amoxicillin alone due to the addition of the beta-lactamase inhibitor.
• Septra would likely be effective against this pan-sensitive E. coli, but it carries higher risks of adverse effects in elderly patients, including increased risk of hyperkalemia, bone marrow suppression, and worsening renal function 1.
• With her existing moderate renal impairment, Septra would require dose adjustment and closer monitoring.
• The European Association of Urology guidelines recommend managing any urological abnormality and/or underlying complicating factors, and using a combination of antibiotics for complicated UTIs, but in this case, oral step-down therapy with amoxicillin-clavulanate is appropriate given the patient's pan-sensitive E. coli and lack of sepsis 1.

Treatment Plan

• Oral amoxicillin-clavulanate 875/125 mg twice daily for a total of 7 days of antibiotic therapy.
• Monitor the patient's renal function and adjust the treatment plan as needed.
• Ensure the patient is able to tolerate the oral medication and is not experiencing any adverse effects.

From the FDA Drug Label

1. 5 Geriatric Use An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. These analyses have not identified differences in responses between the elderly and younger patients, but a 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.
2. 6 Dosing in Renal Impairment Amoxicillin is primarily eliminated by the kidney and dosage adjustment is usually required in patients with severe renal impairment (GFR less than 30 mL/min).

The patient's GFR is 45, which does not require a dosage adjustment for amoxicillin according to the label. Amoxicillin can be used in this patient, but renal function should be monitored. There is no information to support the use of Septra in this context, given the patient's renal function and the potential for electrolyte abnormalities and crystalluria associated with sulfamethoxazole/trimethoprim.

• The patient's baseline renal function is a consideration for the choice of antibiotic.
• Monitoring of renal function is recommended when using amoxicillin in patients with decreased renal function. 2

From the Research

Treatment Options for UTI

The patient is currently being treated with IV ceftriaxone for a UTI caused by pan-sensitive E. coli. Considering the patient's baseline renal function (GFR 45, creatinine 95), the treatment options for stepping down from IV ceftriaxone are:

• Amoxicillin: However, according to 3, amoxicillin/clavulanic acid has a low susceptibility rate (2.27% in children and 2.35% in adults) against E. coli, making it a less favorable option.
• Septra (trimethoprim/sulfamethoxazole): The susceptibility of E. coli to trimethoprim/sulfamethoxazole is not explicitly stated in the provided studies, but 4 reports a prevalence of E. coli resistance to trimethoprim/sulfamethoxazole of 13.0% in uncomplicated UTIs.

Considerations for Stepping Down to Oral Antibiotics

When stepping down to oral antibiotics, it is essential to consider the local susceptibility patterns and resistance rates of the causative organism. According to 5, the recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis includes nitrofurantoin, fosfomycin, or pivmecillinam. However, these options may not be suitable for all patients, and the choice of antibiotic should be based on the individual patient's characteristics and the specific circumstances of the infection.

Renal Function Considerations

The patient's baseline renal function (GFR 45, creatinine 95) should be taken into account when selecting an oral antibiotic. Some antibiotics, such as nitrofurantoin, may require dose adjustments or be contraindicated in patients with impaired renal function. According to 6, nitrofurantoin retains antimicrobial activity against multidrug-resistant urinary E. coli, but its use may be limited in patients with significant renal impairment.

Resistance Patterns and Treatment Guidelines

The increasing resistance rates of E. coli to commonly used antibiotics, such as trimethoprim/sulfamethoxazole, highlight the need for careful consideration of treatment options. As reported in 7, a resistance rate threshold of 19-21% may indicate the need to change first-line empirical antibiotic choice. However, this threshold may vary depending on the local epidemiology and specific patient population.