What antibiotic would you recommend for a 48-year-old woman with irritable bowel syndrome predominant diarrhea?

Rifaximin is the Antibiotic of Choice for IBS-D

For a 48-year-old woman with IBS-D, prescribe rifaximin 550 mg orally three times daily for 14 days. This is the only FDA-approved antibiotic for IBS-D and has the strongest guideline support with a favorable safety profile 1, 2.

Initial Treatment Protocol

• Standard dosing: Rifaximin 550 mg three times daily for 14 days 1, 2
• Expected response: Approximately 41% of patients achieve adequate global symptom relief (versus 32% with placebo), giving a number needed to treat of approximately 11 1, 3
• Assessment window: Evaluate response during the 4 weeks following completion of the 14-day course 1, 2

Mechanism and Benefits

Rifaximin is a non-absorbable antibiotic that modulates gut microbiota and has anti-inflammatory properties 4, 5. The drug demonstrates superiority over placebo for:

• Bloating relief: Risk ratio 0.86 (95% CI 0.70–0.93) 1, 2
• Abdominal pain: Risk ratio 0.87 (95% CI 0.80–0.95) 1, 2
• Stool consistency improvement: Significant benefit demonstrated 1

Retreatment Strategy if Symptoms Recur

If your patient responds initially but symptoms return, retreatment with the same regimen is appropriate 1, 2:

• Up to 2 additional 14-day courses can be given 1, 2
• Retreatment provides 33% response versus 25% with placebo (p=0.02) 3
• Response rates are lower with retreatment compared to initial treatment, but still clinically meaningful 1, 2
• Typical recurrence occurs every 2-3 months after a course 2

Safety Profile

Rifaximin has an excellent safety profile that distinguishes it from other antibiotics 1, 4, 5:

• Adverse events comparable to placebo across all trials 1
• Minimal systemic absorption (<0.4%), so no dose adjustment needed for renal or hepatic impairment 2
• Very low risk of Clostridioides difficile infection due to minimal absorption 2
• No significant bacterial resistance observed in clinical trials 4, 5
• No routine laboratory monitoring required 2

Critical Contraindications and Pitfalls

• Never use rifaximin as monotherapy for C. difficile infection—it is only for adjunctive use after vancomycin in recurrent cases 6
• Rifaximin is contraindicated in patients with known hypersensitivity to rifaximin, rifamycin antimicrobials, or any components 1
• The drug is not appropriate for IBS with constipation (IBS-C)—only for IBS-D 1

If Rifaximin Fails or Is Insufficient

When rifaximin provides inadequate relief after initial treatment and retreatment, escalate therapy algorithmically 1, 7:

Second-line options:

1. Add a probiotic: Bifidobacterium longum 35624, one capsule daily for 8-12 weeks, has the strongest evidence for IBS-D 7

2. Eluxadoline 100 mg twice daily: Effective for predominant diarrhea and urgency, but contraindicated in patients without a gallbladder, with alcohol use disorder, or history of pancreatitis/sphincter of Oddi dysfunction 1

3. Ondansetron: Titrate from 4 mg once daily up to 8 mg three times daily; constipation is the main side effect 1

4. Tricyclic antidepressants: Start amitriptyline 10 mg at bedtime, titrate to 30-50 mg for gut-brain neuromodulation 1, 7

Adjunctive symptomatic therapy:

• Loperamide 4-12 mg daily for diarrhea and urgency control 1, 7
• Low FODMAP diet supervised by a dietitian if dietary triggers are suspected 1, 7
• Screen for bile acid malabsorption (affects ~10% of IBS-D patients) with serum 7α-hydroxy-4-cholesten-3-one; treat with cholestyramine if positive 1, 7

Why Not Other Antibiotics?

• Neomycin: Associated with ototoxicity, nephrotoxicity, and bacterial resistance—not recommended 4
• Metronidazole: Inferior to rifaximin (43.7% vs 63.4% normalization in SIBO studies, p<0.05) with worse tolerability 2
• Conventional systemic antibiotics: Risk of C. difficile infection, resistance, and systemic side effects without proven benefit in IBS-D 4, 5

Practical Implementation

• Counsel the patient that rifaximin is a short-course therapy (14 days), not a daily medication 4
• Explain that symptom relief typically occurs during the 4 weeks after completing treatment 1, 2
• Set realistic expectations: approximately 40% will achieve meaningful relief, and retreatment is an option if symptoms recur 1, 3
• Rifaximin has no significant drug-drug interactions due to minimal absorption, making it safe in polypharmacy 3, 5