Introduction

Pyuria and Asymptomatic Bacteriuria (ASB) are similar conditions with key differences in diagnosis, presentation, clinical significance and management. Pyuria and bacteriuria both relate to the presence of leukocytes (white blood cells) in the urine.¹ The key difference between pyuria and ASB is that pyuria does not always indicate the presence of bacteria in the urine; however, ASB does, whilst not requiring treatment in most cases. ASB and pyuria are extremely common in clinical practice; however, if unnecessarily treated, this can lead to antibiotic resistance and other complications. However, if ASB requires treatment, such as in pregnancy or for specific urologic procedures, and if left untreated, this can also cause complications.² These conditions will be discussed in further detail, including their aetiology, detection, management, and implications of mismanagement. 

Understanding Pyuria

Etiology

Pyuria is defined as a positive urine dipstick for leukocyte esterase (an enzyme) or leukocytes found on urine microscopy, with more than 10 leukocytes per microlitre by haemocytometer. Pyuria may or may not be accompanied by symptoms. It is often used as an important marker in the diagnosis of UTIs such as cystitis (infection of the bladder) or pyelonephritis (infection of the kidneys).³ The most common infectious pathogens that cause pyuria are Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus.⁴

Risk factors for UTIs include women aged between 14-24 and women over the age of 65. Women in general are more prone to UTIs as they have shorter urethras than men, facilitating bacteria to travel up the urethra from the perineum to the bladder. The frequency of uncomplicated UTIs in the United States (US) is approximately 0,5 episodes per person per year, making them the most common outpatient infection in the US. Other risk factors include sexual activity, older age, diabetes mellitus, catheterisation, spinal cord dysfunction and antibiotic use.⁶

Despite infections being the most common cause of pyuria, non-infectious causes of pyuria, which is referred to as sterile pyuria, are not uncommon in clinical practice.⁵ These are caused by inflammation of the urinary tract, some examples including, pelvic malignancy or tuberculosis, renal tract malignancy, previous pelvic surgery radiotherapy, catheter use, renal calculi (stones), polycystic kidneys, systemic lupus erythematosus (SLE), Diabetes, and Nonsteroidal anti-inflammatory (NSAID)/steroid/antibiotic use.⁵

Detection

Pyuria is detected using a urine dipstick, which measures an enzyme produced by white blood cells called leukocyte esterase. If urine microscopy is used, the criteria for diagnosis of pyuria are more than/including 10 leukocytes per microliter.³ However, diagnostic guidelines vary as to the lower limit of pyuria accurately associated with bacterial infection, which requires treatment. 

There is no consensus as to the exact number of cells per microliter correlating with a UTI, however, the result must be correlated clinically. Pyuria has poor sensitivity and specificity in predicting a positive urine culture, indicating infection. Therefore, pyuria alone is an inadequate test to diagnose a UTI, and should be used in conjunction with a positive nitrite result on urine dipstick and/or positive urine culture. Without these additional tests, patients with pyuria who present with nonspecific complaints are often inappropriately treated with antibiotics. This can lead to antibiotic resistance and Clostridioides difficile infection, which causes diarrhoea.³ 

Understanding Asymptomatic Bacteriuria

Diagnosis

By definition, ASB is diagnosed when a urine sample with a significant bacterial count is cultured, without any urinary symptoms such as dysuria (pain on urination), frequency, and urgency (increased sensation of needing to urinate).²

Diagnosis of ASB is made solely by urine culture. Urine dipstick and urinalysis under microscopic exam will only identify pyuria, and will miss bacteriuria.² The diagnostic criteria depend on the sex of the individual and whether the specimen was collected from a midstream urine or catheter sample. For women, two consecutive midstream specimens of the same bacterial species of at least 100,000 colony-forming units (CFU) per ml of urine are required. For men, the same guidelines apply for a single specimen. In catheterised specimens, one bacterial species with at least 100,000 CFU per ml should be cultured.²

Risk factors of ASB and differential diagnosis

Like pyuria, the risk factors for ASB also include the elderly, patients with spinal cord injuries, those with diabetes mellitus and patients with indwelling catheters.² Other risk factors include obstructive uropathy (such as renal stones), faecal soiling of the perineum, and pregnancy.

The differential diagnosis for ASB is acute pyelonephritis, bladder cancer, chlamydia, cystitis, herpes simplex, pelvic inflammatory disease and vaginitis, amongst others.²

Key Differences Between Pyuria and ASB

Clinical Significance and Management

Treatment of ASB

Most patients with ASB will not require antibiotic therapy and will have no adverse consequences. Specifically, children, diabetics, older patients, patients with spinal cord injuries and those with indwelling catheters without symptoms do not benefit from treatment with antibiotics.² Treatment of these groups of patients does not decrease the incidence of symptomatic UTIs or improve survival.²

However, treatment of ASB is indicated in three populations: pregnant women, those undergoing urologic procedures in which mucosal bleeding is expected (such as resection of the prostate) and patients within the three-month window post renal transplant.² Treatment of ASB in pregnancy decreases the risk of pyelonephritis, low-birthweight infants and preterm delivery.² In patients undergoing urologic procedures where bleeding is expected, and those post renal transplant is proven to decrease the risk of symptomatic UTIs.²

Treatment should be informed by the urine culture and sensitivity, and amoxicillin, amoxicillin/clavulanate, cefuroxime, cephalexin and nitrofurantoin are considered safe in pregnancy. Treatment lasts 3-7 days, and at least one follow-up culture should be performed.²

Treatment of pyuria

Treatment of pyuria depends on the presence of bacteriuria. If bacteriuria is present in the urine culture, symptoms of the patient should be assessed. If the patient has urinary symptoms such as frequency, dysuria or urgency, or a fever, abdominal pain and/or vomiting, this could indicate a UTI.⁸ This is an indicator for treatment with antibiotics, orally or intravenously, depending on severity. The type of antibiotic will also vary depending on the sensitivity, which is determined by urine microscopy and culture. According to the Infectious Diseases Society, first-line agents include nitrofurantoin, sulfamethoxazole/trimethoprim, trimethoprim alone, fosfomycin and first-generation cephalosporins.⁸

If pyuria is present without bacteriuria, the clinician should consider sterile pyuria. The most common causes (mentioned above) are tuberculosis of the urogenital tract, urinary stones and renal tract malignancy.⁵ Clinical history, examination, routine haematological tests, vaginal swabs and/or a kidney ultrasound may be needed to identify the underlying cause⁵.

Implications of Mismanagement

As mentioned above, the implications of mismanagement depend on whether ASB is treated unnecessarily or when it is not treated in necessary cases. The former predisposes an individual to antibiotic resistance and diarrhoea caused by Clostridioides difficile, and the latter can cause complications in pregnancy or the development of symptomatic UTIs in those undergoing surgical urologic procedures in which mucosal bleeding is expected, and patients within the three-month window post renal transplant.^2,3

Summary

Pyuria and ASB are similar conditions, yet it is of clinical importance to differentiate between the two. The diagnosis of pyuria is leukocytes in the urine detected by urine dipstick and/or microscopy, while the diagnosis of ASB is made using urine culture only.^1,2 The key difference between pyuria and ASB is that pyuria does not always indicate the presence of bacteria in the urine, however, ASB does, whilst not requiring treatment in most cases.² However, there are negative implications for the mismanagement of ASB depending on whether it is treated unnecessarily or when it is not treated in necessary cases.³ Thus, treatment of both ASB and pyuria requires careful clinical history taking and examination, and appropriate use of special investigations and rational antibiotic prescription if necessary.³