What is the cause of pyuria (presence of pus in urine) with negative urine cultures?

From the Guidelines

Pyuria without bacterial growth on urine cultures does not require antibiotic treatment unless a specific infection is identified, and management should focus on investigating the underlying cause of the inflammation. When considering the diagnosis and treatment of urinary tract issues, it's essential to follow guidelines that prioritize patient outcomes in terms of morbidity, mortality, and quality of life. According to the Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults 1, pyuria accompanying asymptomatic bacteriuria is not an indication for antimicrobial treatment. This suggests that the presence of pyuria alone, without evidence of bacterial infection, should not automatically lead to antibiotic therapy.

Some key points to consider in the management of pyuria without bacterial growth include:

• The condition may be caused by various factors such as partially treated urinary tract infections, kidney stones, interstitial cystitis, genitourinary tuberculosis, or sexually transmitted infections like chlamydia or gonorrhea.
• Management depends on identifying the underlying cause through additional testing such as STI screening, imaging studies, or referral to a urologist.
• Symptomatic relief may include increased fluid intake and over-the-counter pain relievers like acetaminophen or ibuprofen while the cause is being determined.
• Patients should follow up with their healthcare provider if symptoms persist or worsen, as persistent sterile pyuria requires thorough evaluation to rule out serious conditions like genitourinary tuberculosis or urinary tract malignancies.

Given the potential causes and the importance of targeted treatment, a thorough diagnostic approach is necessary to guide appropriate management and prevent unnecessary antibiotic use, as supported by guidelines like those from the Infectious Diseases Society of America 1.

From the Research

Pyuria without Bacterial Growth

• Pyuria, or the presence of white blood cells in the urine, can occur without bacterial growth in urine cultures, as seen in a case of acute focal bacterial nephritis where the patient presented with pyuria but negative urine cultures 2.
• A study of 46,127 patients found that pyuria alone did not provide adequate diagnostic accuracy to predict bacteriuria, and that a urine white blood cell count greater than 25 cell/hpf was the optimal cutoff to detect bacteriuria 3.
• Asymptomatic bacteriuria and pyuria can occur in healthy women, and a study of 104 premenopausal women found that asymptomatic bacteriuria events were uncommon and rarely lasted more than 2 days, while pyuria was common but infrequently associated with bacteriuria or symptoms 4.

Clinical Implications

• The presence of pyuria without bacterial growth in urine cultures can make diagnosis and treatment challenging, and clinicians should consider other potential causes of pyuria, such as inflammation or contamination 5.
• A study of children with positive urine cultures without pyuria found that 70% of children improved before starting antibiotics, but over 80% were ultimately treated, highlighting the need for careful consideration of treatment decisions 6.
• The current guideline recommendation against antibiotic treatment based on urine analysis alone is supported by the findings of a study that found pyuria alone provides inadequate diagnostic accuracy for predicting bacteriuria 3.

Diagnostic Considerations

• The interpretation of pyuria may be especially important in patients with nonspecific complaints, and clinicians should consider the clinical context and other diagnostic findings when interpreting pyuria results 3.
• A study of the correlation of pyuria and bacteriuria in acute care found that the optimal urine white blood cell cutoff was 25 cell/hpf, and that pyuria alone did not provide adequate diagnostic accuracy to predict bacteriuria 3.
• Clinicians should be aware of the potential for asymptomatic bacteriuria and pyuria in healthy individuals, and should consider the potential for false positives or contamination when interpreting urine culture results 4.