What are the next steps in treatment for a patient with persistent dysuria, hematuria, proteinuria, and leukocyturia despite 5 days of nitrofurantoin for E coli urinary tract infection?

From the Guidelines

For a patient with persistent symptoms of dysuria, hematuria, proteinuria, and leukocyturia despite 5 days of nitrofurantoin for E. coli UTI, the next steps should include obtaining a repeat urine culture to check for antibiotic resistance and considering an alternative antibiotic regimen. I recommend switching to a fluoroquinolone such as ciprofloxacin 500 mg twice daily for 7 days, or trimethoprim-sulfamethoxazole (TMP-SMX) 160/800 mg twice daily for 7 days, depending on local resistance patterns, as suggested by the American College of Physicians 1. Extended-spectrum beta-lactamase (ESBL) testing should be performed on the new culture to rule out resistant organisms. Additionally, imaging studies such as renal ultrasound or CT urography should be considered to evaluate for complications like pyelonephritis, renal abscess, or anatomical abnormalities that might be contributing to treatment failure, as recommended by the IDSA/ESCMID guideline 1. The patient should increase fluid intake to at least 2-3 liters daily and follow up within 48-72 hours to assess response to the new treatment. Treatment failure with first-line antibiotics may indicate either bacterial resistance, inadequate drug concentration at the infection site, or a more complicated infection that requires a broader diagnostic workup and potentially longer treatment duration or intravenous antibiotics if the patient's condition worsens. It is also important to consider the patient's prior culture data and local antibiogram to guide antibiotic selection, as well as to avoid treating asymptomatic bacteriuria, which can foster antimicrobial resistance 1. Some key points to consider in the management of this patient include:

• Obtaining a repeat urine culture to assess for ongoing bacteriuria before prescribing additional antibiotics
• Considering alternative antibiotic regimens, such as fluoroquinolones or TMP-SMX, based on local resistance patterns
• Performing ESBL testing to rule out resistant organisms
• Evaluating for complications, such as pyelonephritis or renal abscess, using imaging studies
• Increasing fluid intake and follow-up to assess response to treatment.

From the FDA Drug Label

To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris

The patient has persistent symptoms of dysuria, hematuria, proteinuria, and leukocyturia despite 5 days of nitrofurantoin for E coli urinary tract infection. The next steps in treatment and evaluation are:

• Re-evaluate the patient to ensure the diagnosis of urinary tract infection is correct and consider other possible causes of symptoms.
• Consider alternative antibiotics such as trimethoprim-sulfamethoxazole 2 if the patient has not responded to nitrofurantoin, as the E coli is sensitive to this antibiotic.
• Monitor for complications such as pyelonephritis or sepsis, especially if the patient has underlying medical conditions or is immunocompromised.
• Repeat urinalysis and culture to assess for resolution of infection or development of resistance to nitrofurantoin.

From the Research

Next Steps in Treatment and Evaluation

The patient has been treated with nitrofurantoin for 5 days, but still experiences symptoms of dysuria, hematuria, proteinuria, and leukocyturia. Given the culture report indicates E coli that is sensitive to nitrofurantoin, the following steps can be considered:

• Re-evaluate the patient's symptoms and urinalysis results to determine if the infection is resolving or if there are any signs of complications, such as pyelonephritis or sepsis.
• Consider obtaining a repeat urine culture to assess for persistent infection or development of resistance to nitrofurantoin, as studies have shown that nitrofurantoin resistance can occur, especially in patients with a history of kidney stones 3 or alkaline urine 4.
• Evaluate the patient's kidney function, as reduced kidney function may affect the efficacy of nitrofurantoin, although a study found that mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin 5.
• Consider alternative antibiotic therapies, such as fosfomycin, which has been shown to be effective in treating uncomplicated lower urinary tract infections 6, or other antibiotics like trimethoprim-sulfamethoxazole or ciprofloxacin, which may be more effective in patients with certain risk factors, such as a history of kidney stones 3.
• Monitor the patient for adverse events, such as nausea and diarrhea, which are common with nitrofurantoin use 6, 7.

Potential Causes of Persistent Symptoms

The patient's persistent symptoms despite 5 days of nitrofurantoin treatment may be due to several factors, including:

• Inadequate urine concentration of nitrofurantoin, which may occur in patients with reduced kidney function 5.
• Development of resistance to nitrofurantoin, which can occur, especially in patients with a history of kidney stones 3 or alkaline urine 4.
• Presence of a complicated urinary tract infection, such as pyelonephritis or a urinary tract abnormality, which may require more aggressive treatment.
• Other underlying medical conditions, such as diabetes or immunosuppression, which may increase the risk of developing a complicated urinary tract infection.