What is the best course of action for a patient with leukocytosis and erythrocytosis in the urine, suggestive of a urinary tract infection, but with a urine culture showing no growth, and considering potential underlying conditions such as diabetes?

Management of Pyuria and Hematuria with Negative Urine Culture

Do not treat this patient with antibiotics—the negative urine culture effectively rules out bacterial urinary tract infection, and the elevated leukocytes and erythrocytes with high epithelial cells indicate specimen contamination rather than true infection. 1

Immediate Interpretation of Results

The combination of findings strongly suggests a contaminated specimen rather than true infection:

• High epithelial cell count (79 x 10^6/L) is the critical finding indicating contamination from periurethral or vaginal cells during collection 1
• Negative culture has >95% specificity for ruling out significant bacterial UTI, even with pyuria present 1
• The presence of both leukocytes and erythrocytes with high epithelial cells and no bacterial growth is the classic pattern of a poorly collected specimen 1

Clinical Decision Algorithm

Step 1: Assess for Specific Urinary Symptoms

If the patient has NO specific urinary symptoms (dysuria, frequency, urgency, fever >37.8°C, gross hematuria):

• Stop here—do not pursue further UTI testing or treatment 1, 2
• This represents asymptomatic bacteriuria with pyuria, which should never be treated (except in pregnancy or pre-urologic procedures) 1
• In diabetic patients specifically, asymptomatic bacteriuria is common and treatment provides no clinical benefit 3, 4

If the patient HAS specific urinary symptoms:

• Proceed to Step 2 for proper specimen collection 1

Step 2: Obtain Properly Collected Specimen

The current specimen is unreliable due to contamination. Collect a new specimen using:

• For women: In-and-out catheterization is preferred to avoid perineal/vaginal contamination 1, 2
• For cooperative men: Midstream clean-catch or freshly applied clean condom catheter 1
• Process within 1 hour at room temperature or 4 hours if refrigerated 1

Step 3: Repeat Urinalysis and Culture on Clean Specimen

Only proceed to culture if the clean specimen shows: 1

• Pyuria ≥10 WBCs/HPF, OR
• Positive leukocyte esterase, OR
• Positive nitrite

If repeat specimen still shows high epithelial cells with negative culture:

• Consider non-infectious causes of pyuria and hematuria 1

Alternative Diagnoses to Consider in Diabetic Patients

With sterile pyuria and hematuria in a diabetic patient, evaluate for:

• Interstitial cystitis or bladder inflammation from non-infectious causes 1
• Nephrolithiasis (hematuria with sterile pyuria) 1
• Diabetic nephropathy with microscopic hematuria 4
• Genitourinary tuberculosis (requires specific culture media) 1
• Papillary necrosis (more common in diabetics with UTI complications) 5, 4
• Emphysematous cystitis or pyelonephritis if gas-forming organisms present (though culture would typically be positive) 5

Special Considerations for Diabetes

Diabetes mellitus is classified as a complicating factor for UTI when true infection is present 3:

• Diabetic patients have higher rates of asymptomatic bacteriuria (no treatment indicated) 3, 4
• When symptomatic UTI occurs, treat for 7-14 days (14 days if male to cover possible prostatitis) 3
• Diabetics have increased risk of complicated UTI including pyelonephritis, papillary necrosis, and emphysematous infections 5, 4
• However, asymptomatic bacteriuria in diabetics should NOT be treated—it provides no clinical benefit and increases antibiotic resistance 1, 4

Critical Pitfalls to Avoid

• Never treat based on pyuria alone without symptoms—this leads to unnecessary antibiotic exposure and resistance development 1, 2
• Never assume cloudy or malodorous urine indicates infection—these findings alone do not justify treatment 1
• Never continue antibiotics for contaminated cultures—this provides no benefit and causes harm 1
• Never ignore high epithelial cell counts—this invalidates the entire specimen and requires recollection 1

When to Pursue Further Workup

Consider imaging (renal/bladder ultrasound) if: 1

• Recurrent episodes of sterile pyuria occur
• Persistent hematuria without explanation
• Systemic symptoms (fever, flank pain) suggest upper tract involvement despite negative culture

Consider urology referral for: 2

• Recurrent symptomatic UTIs with proper documentation
• Anatomic abnormalities suspected on imaging
• Persistent symptoms despite appropriate management