What is the recommended H. pylori eradication regimen after Graham‑patch repair of a perforated ulcer in an adult without known drug allergies?

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H. Pylori Eradication After Graham Patch Repair

Start Eradication Therapy Immediately Upon Oral Feeding

Begin H. pylori eradication treatment as soon as oral feeding is reintroduced after Graham patch repair, not after hospital discharge or complete ulcer healing 1, 2. Delaying treatment until discharge leads to reduced compliance and loss to follow-up 1, 2. H. pylori eradication has no effect on early rebleeding rates after surgical repair, so there is no benefit to waiting 2.

Recommended First-Line Regimen: Bismuth Quadruple Therapy

The optimal regimen is bismuth quadruple therapy for 14 days 1, 2, 3:

  • Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs; increases cure rates by 8-12%) 2, 3
  • Bismuth subsalicylate 262 mg (two tablets) four times daily 3
  • Metronidazole 500 mg three to four times daily 1, 3
  • Tetracycline 500 mg four times daily 1, 3

This regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance 1, 3. Bismuth has no described bacterial resistance, and its synergistic effect overcomes metronidazole resistance in vitro 1, 3.

Alternative First-Line Option (If Bismuth Unavailable)

If bismuth is not available and local clarithromycin resistance is documented below 15%, use concomitant non-bismuth quadruple therapy for 14 days 1, 3:

  • Esomeprazole or rabeprazole 40 mg twice daily 3
  • Amoxicillin 1000 mg twice daily 1, 3
  • Clarithromycin 500 mg twice daily 1, 3
  • Metronidazole 500 mg twice daily 1, 3

Do not use standard triple therapy (PPI + clarithromycin + amoxicillin) in most regions, as clarithromycin resistance now exceeds 15-20% in most of North America and Europe, reducing eradication rates to only 70% 3.

Critical Optimization Factors

  • Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 3
  • 14-day duration is mandatory; extending from 7 to 14 days improves eradication by approximately 5% 1, 2, 3, 4
  • Never use once-daily PPI dosing; twice-daily high-dose PPI is required for optimal efficacy 3
  • Avoid pantoprazole (40 mg pantoprazole = only 9 mg omeprazole equivalent) 3

Post-Eradication Management for Perforated Ulcer

Continue PPI therapy until H. pylori eradication is confirmed in complicated duodenal ulcer 1. For gastric ulcers, continue PPI until complete healing is documented at endoscopy 1, 5.

Confirm eradication at least 4 weeks after completing therapy using urea breath test or monoclonal stool antigen test 1, 2, 3. Stop PPI at least 2 weeks before testing to avoid false-negative results 1, 3, 5. Never use serology to confirm eradication, as antibodies persist long after successful treatment 3.

Rationale for Eradication in Perforated Ulcer

H. pylori prevalence in perforated peptic ulcer is approximately 65-70% 6. Eradication after simple closure reduces ulcer recurrence from 26% to near zero 1, 2, 7. Without eradication, recurrence rates exceed 50-60% annually 5. The H. pylori infection rate is significantly higher in patients with recurrent or residual ulcers after perforation repair 7.

Second-Line Therapy (If First-Line Fails)

If bismuth quadruple therapy fails and the patient has no prior fluoroquinolone exposure, use levofloxacin triple therapy for 14 days 1, 2, 3:

  • Esomeprazole or rabeprazole 40 mg twice daily 3
  • Amoxicillin 1000 mg twice daily 3
  • Levofloxacin 500 mg once daily 1, 3

Never repeat clarithromycin if it was in the failed regimen; resistance develops rapidly after exposure, dropping eradication rates from 90% to 20% 3.

Third-Line Options

After two failed eradication attempts with confirmed adherence, obtain antibiotic susceptibility testing to guide further treatment 1, 3, 8. Consider rifabutin triple therapy for 14 days 2, 3:

  • Esomeprazole or rabeprazole 40 mg twice daily 3
  • Rifabutin 150 mg twice daily 3
  • Amoxicillin 1000 mg twice daily 3

Special Considerations for Perforated Ulcer

All patients with perforated peptic ulcer should undergo H. pylori testing 1. Testing can be performed via endoscopic biopsy (if endoscopy is done), urea breath test (88-95% sensitivity), or stool antigen testing (94% sensitivity) 1. Avoid testing during the acute phase if possible, as diagnostic tests show 25-55% false-negative rates during acute upper GI bleeding or perforation 2.

Empirical antimicrobial therapy without H. pylori confirmation is not recommended 1. The prevalence of H. pylori in perforated ulcer varies by region and NSAID use, making test-and-treat more cost-effective than empirical therapy 1.

Critical Pitfalls to Avoid

  • Do not delay eradication therapy beyond reintroduction of oral feeding 1, 2
  • Do not use 7-day regimens; 14 days is the evidence-based standard 1, 3, 4
  • Do not skip confirmation testing in complicated peptic ulcer disease 1
  • Do not assume low clarithromycin resistance without local surveillance data; most regions now have high resistance 3
  • Do not use standard-dose PPI once daily; this is a major cause of treatment failure 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

H. Pylori Eradication After Peptic Ulcer Stabilization

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Helicobacter Pylori Infection Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Optimum duration of regimens for Helicobacter pylori eradication.

The Cochrane database of systematic reviews, 2013

Guideline

Ulcer Healing and Management After H. pylori Eradication

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Helicobacter pylori eradication therapy.

Future microbiology, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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