How to manage a patient with a positive leukocyte (White Blood Cell - WBC) esterase in urine but initial negative WBC in urine, suggestive of a urinary tract infection (UTI)?

From the Guidelines

Empiric antibiotic treatment should be initiated in patients with positive leukocyte esterase but negative WBCs in urine if they have symptoms suggestive of a urinary tract infection (UTI). The presence of leukocyte esterase indicates inflammation, which may be due to a UTI, even if WBCs are not visible in the urine 1.

Management of Uncomplicated UTI

For uncomplicated cases, first-line options include:

• Nitrofurantoin 100mg twice daily for 5 days
• Trimethoprim-sulfamethoxazole (TMP-SMX) 160/800mg twice daily for 3 days
• Fosfomycin 3g single dose These options are recommended based on the most recent guidelines and studies, including the ACR Appropriateness Criteria for recurrent lower urinary tract infections in females 1.

Management of Complicated UTI

For patients with risk factors for complicated UTI, consider:

• Fluoroquinolones like ciprofloxacin 250mg twice daily for 7 days
• Cephalexin 500mg four times daily for 7 days It is essential to collect a urine culture before starting antibiotics to guide therapy if symptoms persist 1.

Additional Recommendations

Patients should increase fluid intake, void frequently, and return if symptoms worsen or don't improve within 48-72 hours. For recurrent UTIs, consider longer treatment courses and urologic evaluation to identify underlying anatomical or functional abnormalities 1. The discrepancy between positive leukocyte esterase and negative WBCs may occur because leukocyte esterase detects enzymes from lysed WBCs, indicating inflammation even when intact cells aren't visible.

Key Considerations

When managing patients with recurrent UTIs, it is crucial to avoid classifying them as "complicated" unless they have underlying structural or functional abnormalities of the urinary tract, immune suppression, or pregnancy 1. Additionally, treatment of asymptomatic bacteriuria should be avoided, as it can foster antimicrobial resistance and increase the number of recurrent UTI episodes 1.

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 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 It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination

The patient has a positive leukocyte esterase in urine but initial negative WBC in urine, which is suggestive of a urinary tract infection (UTI).

• The presence of leukocyte esterase in urine indicates the presence of white blood cells, which is a sign of infection.
• The initial negative WBC in urine may be due to various factors such as low bacterial load or inadequate urine sample.
• Treatment with antibiotics such as sulfamethoxazole and trimethoprim 2 or amoxicillin-clavulanate 3 may be considered, but it is essential to confirm the diagnosis with further testing, such as urine culture, to ensure appropriate treatment.
• It is crucial to select an appropriate antibiotic based on the susceptibility of the causative organism and to monitor the patient's response to treatment.

From the Research

Management of Urinary Tract Infection (UTI)

• A patient with a positive leukocyte esterase in urine but initial negative WBC in urine may still be suggestive of a urinary tract infection (UTI) 4, 5.
• Uncomplicated UTIs diagnosed by positive leukocyte esterase and nitrite tests can be treated without culture 4.
• The recommended first-line empiric antibiotic therapy for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantoin, a 3-g single dose of fosfomycin tromethamine, or a 5-day course of pivmecillinam 6.
• Second-line options include oral cephalosporins such as cephalexin or cefixime, fluoroquinolones and β-lactams, such as amoxicillin-clavulanate 6.

Diagnostic Considerations

• Pyuria is the best determinate of bacteriuria requiring therapy, and values significant for infection differ depending on the method of analysis 5.
• A hemocytometer yields a value of > or = 10 WBC/mm3 significant for bacteriuria, while manual microscopy studies show > or = 8 WBC/high-power field reliably predicts a positive urine culture 5.
• Automated urinalysis provides more sensitive detection of leukocytes and bacteria in the urine, and a value of > 2 WBC/hpf is significant pyuria indicative of inflammation of the urinary tract 5.

Treatment Options

• Single-dose trimethoprim-sulfamethoxazole is as effective as ten-day treatment in women with symptoms suggestive of lower urinary tract infection and has no greater relapse rate 7.
• Single-dose therapy for the treatment of urinary-tract infections was simple, effective and well tolerated, and patients preferred taking their treatment in this manner 8.
• Failure of single-dose therapy to eradicate bacteriuria may indicate which patients require subsequent investigations of their urinary tract 8.