What is the diagnosis for a patient with dysuria, frequency, pyuria, low-grade fever, and negative urine culture, with no recent antibiotic use and negative nitrites?

Sterile Pyuria Syndrome

The most likely diagnosis is sterile pyuria, which requires evaluation for non-bacterial causes of urinary tract inflammation including urethritis from sexually transmitted infections (particularly Chlamydia trachomatis and Neisseria gonorrhoeae), tuberculosis, fungal infection, urolithiasis, or interstitial cystitis. 1, 2

Diagnostic Reasoning

The clinical presentation of dysuria, frequency, pyuria (≥10 WBCs/HPF), and low-grade fever with a negative standard urine culture defines sterile pyuria—a scenario where urinary inflammation exists without typical bacterial growth. 1, 3

Why Standard UTI is Unlikely

• Pyuria with negative culture contradicts typical bacterial cystitis, where organisms like E. coli or S. saprophyticus would grow on standard media 4
• Negative nitrites further argue against typical uropathogens, as most gram-negative bacteria (which cause 80-90% of UTIs) convert nitrate to nitrite 1
• The absence of recent antibiotic use eliminates the most common cause of culture-negative UTI—partially treated infection 1

Most Likely Etiologies to Pursue

1. Sexually Transmitted Urethritis (Most Common in Young Adults)

• Chlamydia trachomatis and Neisseria gonorrhoeae cause dysuria and pyuria but don't grow on standard urine culture media 2
• These organisms require specific nucleic acid amplification testing (NAAT) on first-void urine 2
• Consider this diagnosis especially in sexually active patients under 35 years 2

2. Genitourinary Tuberculosis

• TB can present with sterile pyuria, low-grade fever, and urinary symptoms for weeks to months 2
• Requires three early-morning urine specimens for acid-fast bacilli culture and PCR 2
• Consider in patients with TB risk factors (endemic areas, immunosuppression, prior TB exposure) 2

3. Fungal Cystitis

• Candida species don't always grow on routine bacterial culture media 2
• More common in diabetics, immunocompromised patients, or those with recent broad-spectrum antibiotic use 2

4. Urolithiasis with Secondary Inflammation

• Stones cause mechanical irritation leading to pyuria without infection 2
• The low-grade fever could represent inflammatory response rather than infection 2

5. Interstitial Cystitis/Bladder Pain Syndrome

• Chronic condition causing dysuria and frequency with sterile pyuria 2
• Typically lacks fever, making this less likely in this acute presentation 2

Recommended Diagnostic Workup

Immediate next steps should include:

• NAAT testing for Chlamydia and Gonorrhea on first-void urine (highest yield in sexually active patients) 2
• Three early-morning urine specimens for AFB culture and TB PCR (if TB risk factors present) 2
• Fungal culture of urine (especially if diabetic or immunocompromised) 2
• Renal/bladder ultrasound to evaluate for stones or anatomic abnormalities 5, 2
• Consider requesting laboratory to report lower colony counts (10²-10⁴ CFU/mL), as some true UTIs present with lower bacterial counts than the traditional 10⁵ threshold 4

Critical Pitfalls to Avoid

• Do not empirically treat with standard UTI antibiotics without identifying the causative organism, as this will not address non-bacterial causes and contributes to resistance 1
• Do not dismiss the diagnosis as "asymptomatic bacteriuria"—the presence of symptoms (dysuria, frequency, fever) with pyuria indicates true inflammation requiring investigation 1, 6
• Do not assume contamination without proper specimen collection—if initial specimen was midstream clean-catch in a woman, consider catheterized specimen to rule out contamination 5
• In neutropenic patients, significant bacteriuria can occur without pyuria, but this patient has pyuria, so neutropenia is less likely 5

When to Treat Empirically

Hold empiric antibiotics until specific pathogen identified, unless the patient develops signs of systemic infection (high fever >38.5°C, rigors, hemodynamic instability, or flank pain suggesting pyelonephritis), in which case broader coverage including atypical organisms may be warranted while awaiting specialized testing. 7, 1