Recurrent UTI with Negative Culture: Interstitial Cystitis/Bladder Pain Syndrome Evaluation
This patient requires evaluation for interstitial cystitis/bladder pain syndrome (IC/BPS) or other non-infectious causes of her symptoms, as she has recurrent dysuria and frequency with negative urine cultures despite multiple antibiotic courses.
Critical Clinical Context
This patient's presentation is not consistent with recurrent bacterial UTI because:
- Negative urine culture despite symptoms rules out bacterial infection 1
- Trace WBCs, ketones, and occult blood on UA are non-specific findings that do not confirm infection 1
- Pyuria (trace WBCs) is commonly found in the absence of infection, particularly in patients with lower urinary tract symptoms 1
- She has already failed appropriate antibiotic therapy (ciprofloxacin and trimethoprim-sulfamethoxazole) without resolution 2
Common pitfall to avoid: Treating negative cultures with antibiotics increases antimicrobial resistance without clinical benefit and does not address the underlying cause 2.
Immediate Next Steps
1. Stop Empirical Antibiotics
- Do not prescribe additional antibiotics without positive culture confirmation 2, 1
- Continuing antibiotics for culture-negative symptoms promotes resistance and provides no benefit 2
2. Evaluate for Alternative Diagnoses
Consider topiramate-induced urolithiasis:
- Topiramate causes metabolic acidosis and can lead to calcium phosphate stone formation 1
- The presence of ketones and occult blood on UA supports this possibility 1
- Order: Renal ultrasound or non-contrast CT scan to evaluate for stones
Evaluate for interstitial cystitis/bladder pain syndrome:
- Classic presentation: recurrent dysuria, frequency, and urgency without positive cultures 1, 3
- Symptoms persist despite antibiotic treatment 3
- Refer to urology for cystoscopy and IC/BPS evaluation 4
Rule out other causes of dysuria:
- Vaginitis or vulvar lesions (perform pelvic examination) 3
- Chemical or physical irritants 3
- Atrophic vaginitis (consider in perimenopausal women) 2
3. Obtain Post-Void Residual
- Measure post-void residual to assess for incomplete bladder emptying 4
- Elevated PVR suggests functional or anatomical obstruction requiring further urological evaluation 4
If Future Symptomatic Episodes Occur
Only treat with antibiotics if:
- Urine culture is positive (≥10³ CFU/mL in symptomatic women) 1
- Patient has documented bacteriuria with symptoms 1
If culture is positive, first-line treatment options include:
- Nitrofurantoin 100 mg twice daily for 5 days (E. coli resistance only 2-5%) 2, 5
- Fosfomycin 3 g single dose 2, 5
- Avoid fluoroquinolones for uncomplicated UTI due to resistance and adverse effects 2, 5
Medication Review
Topiramate considerations:
- Associated with urolithiasis, metabolic acidosis, and urinary symptoms 1
- Discuss with neurology whether alternative seizure medications are appropriate
- If topiramate must be continued, ensure adequate hydration and consider alkalinizing agents
Prevention Strategies (Only if True Bacterial UTI is Confirmed)
If future culture-proven UTIs occur (≥3 per year):
- Methenamine hippurate for prophylaxis in women without urinary tract abnormalities 2
- Vaginal estrogen therapy if postmenopausal 2
- Continuous low-dose nitrofurantoin 50-100 mg daily for 6-12 months only after non-antimicrobial interventions fail 2
Key Pitfalls to Avoid
- Do not treat culture-negative "UTI" symptoms with antibiotics - this increases resistance without benefit 2, 1
- Do not assume recurrent symptoms equal recurrent infection - negative cultures require alternative diagnosis 1, 3
- Do not overlook medication-induced urinary symptoms - topiramate is a known culprit 1
- Do not delay urological referral - persistent symptoms with negative cultures warrant cystoscopy 4