What is the next treatment for a patient with leukocytosis (White Blood Cell count) in urinalysis and a negative urine culture, who still has symptoms after treatment with Macrobid (Nitrofurantoin)?

From the Guidelines

For a patient with persistent symptoms of urinary tract infection (UTI), leukocytosis in urinalysis, and a negative urine culture after Macrobid treatment, the next appropriate treatment would be a fluoroquinolone such as ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg once daily for 5 days, as recommended by the European Association of Urology guidelines on urological infections 1. This change in antibiotic class is recommended when initial therapy fails, as the causative organism may be resistant to nitrofurantoin or may be located in deeper tissue where nitrofurantoin doesn't achieve adequate concentrations. The presence of white blood cells in the urine despite a negative culture suggests either a partially treated infection, an atypical organism not detected by standard culture methods (like Chlamydia or Mycoplasma), or non-infectious inflammation.

Some key points to consider in the management of this patient include:

• The patient's symptoms and urinalysis results suggest a possible urinary tract infection that has not been fully resolved with Macrobid treatment.
• The negative urine culture may indicate a partially treated infection, an atypical organism, or non-infectious inflammation.
• Fluoroquinolones, such as ciprofloxacin or levofloxacin, are effective treatments for urinary tract infections and can be used as an alternative to Macrobid in cases where the initial treatment has failed.
• Patients should complete the full course of antibiotics even if symptoms improve, and increase fluid intake to help flush the urinary system.
• If symptoms persist after fluoroquinolone therapy, further evaluation is warranted, including consideration of interstitial cystitis, kidney stones, or anatomical abnormalities, as recommended by the European Association of Urology guidelines on urological infections 1.

It's also important to note that the choice of antibiotic should be based on local resistance patterns and patient-specific factors, such as allergy history and renal function, as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases 1. Additionally, patients with recurrent episodes of urinary tract infections may require urological evaluation with possible imaging studies to rule out structural abnormalities.

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 still has symptoms after treatment with Macrobid (Nitrofurantoin) and has a negative urine culture, but leukocytosis is present in the urinalysis. Consideration of alternative antibiotics is necessary.

• Sulfamethoxazole and trimethoprim 2 can be considered for the treatment of urinary tract infections due to susceptible strains of certain organisms.
• However, culture and susceptibility information should be considered in selecting or modifying antibacterial therapy. Since the urine culture is negative, it is unclear what organism is causing the infection, and therefore, the best course of treatment is uncertain.

From the Research

Next Treatment Options

• For a patient with leukocytosis in urinalysis and a negative urine culture, who still has symptoms after treatment with Macrobid (Nitrofurantoin), the next treatment options can be considered based on the following evidence:

Alternative Antibiotics

• Trimethoprim-sulfamethoxazole (TMP-SMX) may be a viable option, as studies have shown its effectiveness in treating urinary tract infections (UTIs) 3, 4.
• Fluoroquinolones, such as ciprofloxacin or levofloxacin, may also be considered, although resistance rates should be taken into account 5, 6.

Considerations for Treatment Selection

• The patient's history of recurrent UTIs and prior exposure to fluoroquinolones should be considered when selecting a treatment, as these factors may increase the risk of resistance to certain antibiotics 6.
• The use of nitrofurantoin as a first-line treatment for uncomplicated UTIs is supported by studies, but alternative treatments may be necessary in cases where nitrofurantoin is not effective or cannot be used 7.

Treatment Duration and Efficacy

• Single-dose trimethoprim-sulfamethoxazole has been shown to be as effective as 10-day treatment for women with symptoms suggestive of lower urinary tract infection, with no greater relapse rate 4.