What is the treatment for severe peptic ulcer disease?

Treatment for Quadruple Therapy in H. pylori-Associated Peptic Ulcer Disease

For peptic ulcer disease requiring quadruple therapy, initiate bismuth-based quadruple therapy (PPI + bismuth + metronidazole + tetracycline) for 14 days when first-line triple therapy has failed or in areas with high clarithromycin resistance (>20%). 1

First-Line Treatment Selection

The choice of initial therapy depends on local clarithromycin resistance patterns:

Low Clarithromycin Resistance Areas (<20%)

• Standard triple therapy for 14 days: PPI (omeprazole 20 mg or equivalent) twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily 1, 2, 3, 4
• This regimen achieves H. pylori eradication rates of 77-90% 4
• Start therapy after 72-96 hours of intravenous PPI administration in bleeding ulcers 2

High Clarithromycin Resistance Areas (>20%)

• Sequential therapy for 10 days: PPI + amoxicillin for 5 days, followed by PPI + clarithromycin + metronidazole for 5 days 2, 3
• Alternatively, bismuth-based quadruple therapy can be used as first-line treatment 1

Second-Line Treatment (After First-Line Failure)

When standard triple therapy fails, switch to levofloxacin-amoxicillin triple therapy or bismuth-based quadruple therapy without waiting for culture results. 2

• Levofloxacin-based triple therapy: PPI + levofloxacin + amoxicillin for 10-14 days 2
• This represents the most practical second-line approach before resorting to culture-guided therapy

Third-Line Treatment

• Culture and antibiotic susceptibility testing should guide third-line therapy selection 1
• Treatment should be tailored based on resistance patterns identified

Acid Suppression Duration Based on Ulcer Type

Uncomplicated Duodenal Ulcer

• Prolonged PPI therapy after H. pylori eradication is NOT recommended 1
• Successful eradication achieves healing rates >90% without additional acid suppression 1
• Omeprazole 20 mg once daily heals 82% of duodenal ulcers within 4 weeks 4

Gastric Ulcer and Complicated Duodenal Ulcer

• Continue PPI therapy after eradication treatment until complete healing is confirmed 1
• Gastric ulcers require longer acid inhibition than duodenal ulcers 1
• Endoscopic follow-up is mandatory to ensure complete gastric ulcer healing 1
• PPI should be continued in complicated duodenal ulcers until H. pylori eradication is confirmed 1

Timing of H. pylori Treatment in Bleeding Ulcers

Start H. pylori eradication therapy immediately when oral feeding is reintroduced after bleeding ulcer, not after discharge. 1, 2

• Delaying treatment until discharge reduces compliance and increases loss to follow-up 1
• H. pylori eradication has no effect on early rebleeding rates but effectively prevents recurrent bleeding long-term 1
• Empirical treatment is cost-effective even in populations with lower H. pylori prevalence (43-56% in bleeding ulcers) 1

High-Dose PPI Protocol for Bleeding Ulcers

• Omeprazole 80 mg IV bolus followed by 8 mg/hour continuous infusion for 72 hours 3
• After endoscopic hemostasis, continue high-dose PPI therapy 3
• Patients can resume oral intake 4-6 hours after endoscopy if hemodynamically stable 3

Confirmation of Eradication

Test for H. pylori eradication at least 4 weeks after completing therapy and at least 2 weeks after stopping PPI. 1, 3

• Use urea breath test (sensitivity 88-95%) or stool antigen test (sensitivity 94%) 3
• Testing period of 4 weeks is adequate; extending to 6-8 weeks is not supported by evidence 1
• Eradication confirmation is mandatory for gastric ulcers 1

Common Pitfalls to Avoid

• Do not delay H. pylori treatment in bleeding ulcers until after discharge - this significantly reduces treatment compliance 1
• Do not continue prolonged PPI therapy for uncomplicated duodenal ulcers after successful eradication - this is unnecessary and increases costs 1
• Do not skip endoscopic follow-up for gastric ulcers - malignancy must be excluded 1, 3
• Do not test for eradication while patient is still on PPI - wait at least 2 weeks after PPI discontinuation to avoid false negatives 3
• Do not use triple therapy in high clarithromycin resistance areas - eradication rates drop significantly 1, 2

NSAID-Associated Ulcers

When NSAIDs cannot be discontinued:

• Switch to less gastrotoxic NSAIDs (e.g., from ketorolac to ibuprofen) 5
• Add PPI therapy (omeprazole or lansoprazole) 5
• Eradicate H. pylori if present 5
• This combination reduces recurrence rates from 40% to 9% 5
• Discontinuing NSAIDs alone heals 95% of ulcers and reduces recurrence from 40% to 9% 5