How to manage a patient with a nitrite positive but leukocyte esterase (LE) negative urine test result, especially with a small sample size, suggesting a possible urinary tract infection (UTI)?

From the Guidelines

A nitrite positive but leukocyte esterase negative urine test result, even with a small sample size, should prompt further evaluation for a urinary tract infection (UTI) and consideration of empiric antibiotic therapy. The presence of nitrite in the urine is a specific indicator of bacteriuria, particularly due to gram-negative enteric bacteria, as noted in a study published in the Annals of Emergency Medicine 1. This suggests that the patient may have a UTI, despite the negative leukocyte esterase result.

The recommended approach is to collect a clean-catch midstream urine sample for culture before starting empiric antibiotic therapy. While awaiting culture results, empiric treatment with nitrofurantoin 100mg twice daily for 5 days (for uncomplicated cases) or trimethoprim-sulfamethoxazole 160/800mg twice daily for 3 days is appropriate if the patient is symptomatic, as the presence of nitrite has a high specificity for UTI 1. Key considerations include:

• The patient's symptoms and medical history
• The potential for asymptomatic bacteriuria, especially in pregnant patients
• The possibility of complicated UTIs, which may require extended treatment

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

• The negative leukocyte esterase result may occur due to dilute urine, early infection, or certain bacterial species that don't trigger significant pyuria
• Patients should be advised to increase fluid intake, complete the full antibiotic course, and follow up if symptoms persist
• For recurrent UTIs, further investigation with imaging or urological consultation may be warranted, as suggested by the clinical policy for children younger than three years presenting to the emergency department with fever 1.

From the Research

Managing a Patient with a Nitrite Positive but Leukocyte Esterase Negative Urine Test Result

• A nitrite positive result indicates the presence of gram-negative bacteria, which are common causes of urinary tract infections (UTIs) 2.
• However, a leukocyte esterase (LE) negative result may not necessarily rule out a UTI, especially with a small sample size 2.
• Studies have shown that the positive predictive value (PPV) of the nitrite test is high (96%) for all samples, while the PPV of a negative nitrite with a positive LE test is also high (79%) 2.

Considerations for Empirical Treatment

• For female patients with symptoms of an acute uncomplicated UTI, a positive nitrite test or a negative nitrite test with a positive LE test can confirm UTI, while a negative nitrite together with a negative LE test does not rule out infection 2.
• The absence of urinary nitrite should not affect routine empiric antibiotic choice for presumptive UTI in young children, as the prevalence of enterococcal UTI is low (3.2%) 3.
• Urinary nitrite results should not be used to guide antimicrobial therapy, as there is no statistically significant difference in the proportion of isolates sensitive to trimethoprim/sulfamethoxazole (TMP/SMX) between nitrite positive and negative groups 4.

Antibiotic Resistance and Treatment

• The resistance rate is higher in the nitrite positive group for certain antibiotics, such as TMP/SMX and ampicillin with or without sulbactam 5.
• Nitrofurantoin or cephalexin may be optimum treatments for cystitis, with nitrofurantoin preferable in the presence of negative leukoesterase 5.
• In the elderly, the aetiology of infection is age-dependent, and the susceptibility of uropathogens to certain antibiotics, such as amoxicillin and trimethoprim, is lower 6.