What is the most appropriate next step in managing a woman with suspected interstitial cystitis presenting with urinary urgency, frequency, suprapubic pain, negative urine cultures, and ongoing antibiotic therapy?

Management of Suspected Interstitial Cystitis with Ongoing Antibiotic Therapy

Stop the antibiotics immediately—interstitial cystitis/bladder pain syndrome (IC/BPS) is not an infection and antibiotic therapy provides no benefit while increasing resistance and potentially worsening symptoms. 1, 2

Immediate Actions

Discontinue Inappropriate Treatment

• Antibiotics must be stopped as there is no underlying infection in IC/BPS, and continued antimicrobial therapy is contraindicated 2
• Amoxicillin and ampicillin specifically should never be used empirically given very high resistance rates worldwide, but more importantly, they are irrelevant here since this is not a bacterial infection 1

Confirm the Diagnosis

• Document that symptoms have been present for at least 6 weeks with negative urine cultures to meet diagnostic criteria 1
• Establish baseline pain levels and voiding frequency using a voiding diary (minimum one day) to measure treatment response 1
• Perform cystoscopy only if Hunner lesions are suspected, as this is the only consistent cystoscopic finding diagnostic for IC/BPS 1
• Most patients do not require cystoscopy for diagnosis unless Hunner lesions are suspected or to rule out bladder cancer, stones, or foreign bodies 1

First-Line Treatment Approach

Patient Education (Critical Foundation)

• Explain that IC/BPS is a chronic disorder requiring continual management, not a curable infection 1
• Set realistic expectations: no single treatment works for the majority of patients, and acceptable symptom control may require trials of multiple therapies 1
• Inform the patient that the typical course involves symptom exacerbations and remissions 1

Behavioral and Non-Pharmacologic Interventions (Start Immediately)

• Dietary modification: Identify and avoid bladder irritants through an elimination diet 1
• Fluid management: Alter urine concentration and volume through strategic hydration 1
• Stress management: Implement techniques like meditation and imagery, as psychological stress heightens pain sensitivity in IC/BPS patients 1
• Pelvic floor muscle relaxation: Avoid exercises that worsen symptoms; apply heat or cold to bladder/perineum 1
• Bladder training with urge suppression to manage constant urge sensations 1
• Address constipation and avoid tight-fitting clothing if these worsen symptoms 1

Pharmacologic Treatment Algorithm

First-Line Oral Medication: Amitriptyline

• Start amitriptyline at 10 mg nightly and titrate slowly 1
• Amitriptyline has Grade B evidence showing superiority over placebo for IC/BPS symptom improvement 1
• Common pitfall: Adverse effects (sedation, drowsiness, nausea) are common and can compromise quality of life, but are not life-threatening 1
• Begin at low doses to minimize side effects while achieving therapeutic benefit 1

Multimodal Oral Therapy (If Monotherapy Insufficient)

• Add hydroxyzine (antihistamine) to address mast cell activation 3
• Consider adding amitriptyline if not already started, as the combination of pentosan polysulfate + antihistamine + tricyclic antidepressant has shown benefit 3
• Critical warning about pentosan polysulfate (PPS): Recent findings of pigmented maculopathy with chronic PPS use are very concerning and must be discussed with patients; many will choose not to start or to discontinue this medication 4

Intravesical "Rescue" Therapy (For Acute Flares)

• Lidocaine and heparin instillations can provide immediate relief while oral medications take effect 3
• DMSO (dimethyl sulfoxide) instillations: 50 mL instilled directly into bladder via catheter, retained for 15 minutes, repeated every 2 weeks until maximum symptomatic relief 5
• Apply lidocaine jelly to urethra before catheter insertion to prevent spasm 5
• Consider oral analgesics or belladonna/opium suppositories before instillation to reduce bladder spasm 5
• In severe cases with very sensitive bladders, perform initial treatments under anesthesia (saddle block suggested) 5

Special Considerations for Hunner Lesions

If cystoscopy reveals Hunner lesions:

• Early diagnosis and treatment are recommended without requiring failure of behavioral or medical treatments first 1
• Most patients with Hunner lesions will respond to specific treatment 1
• This represents a distinct phenotype within IC/BPS requiring targeted intervention 1

Pain Management Principles

• Avoid chronic opioids due to the global opioid crisis; use only after informed shared decision-making with periodic follow-ups to assess efficacy, adverse events, compliance, and potential abuse 1
• Non-opioid alternatives should be used preferentially for pain management 1
• Pain management alone does not constitute sufficient treatment—a multimodal approach combining pharmacologic agents with behavioral therapies is most effective 1
• Treat underlying bladder-related symptoms, not just pain 1

Follow-Up Strategy

• Schedule frequent follow-up visits to assess treatment response and adjust therapy 6
• Reassess voiding symptoms and pain levels at each visit using the baseline measurements 1
• Be prepared to trial multiple therapeutic options including combination therapy before achieving acceptable symptom control 1
• Consider referral to a multidisciplinary team if symptoms remain refractory 1