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2017 ACG Guidelines for Peptic Ulcer Disease
Guidelines for the Indications to Test for, and to Treat, H. pylori Infection
Guidelines for First line Treatment Strategies of Peptic Ulcer Disease for Providers in North America
Guidlines for factors that predict the successful eradication when treating H. pylori infection
Guidelines to document H. pylori antimicrobial resistance in the North America
Guidelines for evaluation and testing of H. pylori antibiotic resistance
Guidelines for when to test for treatment success after H. pylori eradication therapy
Guidelines for penicillin allergy in patients with H. pylori infection
Guidelines for the salvage therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

Eradication of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal peptic ulceration, who are colonized with H. pylori, and patients with MALT lymphoma. Eradication therapy should also be considered in patients with immune thrombocytopenic purpura who are H. pylori-positive and patients who have undergone resection for early-stage gastric cancer. Pharmacologic therapies for peptic ulcer disease due to H. pylori is either triple or quadruple pharmacologic agents that include a Proton pump inhibitors plus a combination of antimicrobial agents. The use of antimicrobial therapy is discouraged among asymptomatic carriers.

Medical Therapy

The mainstay of treatment for peptic ulcer disease is pharmacotherapy. Pharmacotherapy for peptic ulcer disease can be discussed under Helicobacter pylori-associated peptic ulcer and Non- Helicobacter pylori-associated peptic ulcer disease.

Eradication Therapy for Helicobacter pylori Infection

The ACG’s 2007 treatment guideline on the management of H. pylori infection listed the following as established indications for diagnosis and treatment:

Indications

• Active PUD (gastric or duodenal).
• Confirmed history of PUD (not previously treated for H. pylori)
• Gastric MALT lymphoma (low grade)
• After endoscopic resection of EGC
• Depending upon exposure of antibiotics and allergy to antibiotics ,following treatments regimen are being used :

Triple Therapy

• Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or metronidazole for 14 days remains a recommended treatment in regions where H. pylori clarithromycin resistance is known to be <15% and in patients with no previous history of macrolide exposure for any reason.
• PCA regimen

• Preferred regimen (1):Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
• Note: Lansoprazole 30 mg q12h, or Omeprazole 20 mg q12h, or Esomeprazole 40 mg q24h, or Rabeprazole 20 mg q12h
• Preferred regimen (2):Clarithromycin (500 mg twice daily) for 7–14 days AND
• Preferred regimen (3):Amoxicillin (1 g twice daily) for 7–14 days OR Metronidazole (250 mg four times daily) for 7–14 days

• PCM regimen

• Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
• Alternative regimen (2): Clarithromycin (500 mg twice daily) for 7–14 days AND
• Alternative regimen (3): Metronidazole (250 mg four times daily) for 7–14 days

• PLA regimen

• Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 10 days AND
• Alternative regimen (2): Levofloxacin (500 mg twice daily) for 10 days AND
• Alternative regimen (3): Amoxicillin (1 g twice daily) for 10 days

• PMA regimen

• Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
• Alternative regimen (1): Metronidazole (250 mg four times daily) for 7–14 days AND
• Alternative regimen (1): Amoxicillin (1 g twice daily) for 7–14 days

• PRA regimen

• Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 10 days AND
• Alternative regimen (1): Rifabutin (150–300 mg/day) for 10 days AND
• Alternative regimen (1): Amoxicillin (1 g twice daily) for 10 days

• Bismuth quadruple therapy

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
• Preferred regimen (1): Metronidazole (250 mg four times daily) for 10–14 days AND
• Preferred regimen (1): Tetracycline (500 mg four times daily) for 10–14 days AND
• Preferred regimen (1): Bismuth (dose depends on preparation) for 10–14 days

Bismuth-Containing Quadruple Therapy

• Bismuth quadruple therapy particularly attractive in patients with any previous macrolide exposure or clarithromycin resistance is known to be high or who are allergic to penicillin

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
• Preferred regimen (2): Metronidazole (250 mg four times daily) for 10–14 days AND
• Preferred regimen (3): Tetracycline (500 mg four times daily) for 10–14 days AND
• Preferred regimen (4): Bismuth (dose depends on preparation) for 10–14 day

Non–Bismuth-Containing Quadruple Therapy

• Concomitant therapy.

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
• Preferred regimen (2): Clarithromycin (500 mg twice daily) for 10–14 days AND
• Preferred regimen (3): Amoxicillin (1 g twice daily) for 10-14 days AND
• Preferred regimen (4): Nitroimidazole (250 mg four times daily) for 10–14 days

• Sequential therapy.:

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 5-7 days AND
• Preferred regimen (2): Amoxicillin (1 g twice times daily) for 5-7 days
  FOLLOWED BY
• Preferred regimen (3): Proton pump inhibitor (standard dose twice daily) for another 5-7days AND
• Preferred regimen (4): Clarithromycin (500 mg twice daily) for another 5-7 days AND
• Preferred regimen (5): Tinidazole (500 mg twice daily) for another 5-7 days

• Hybrid therapy:

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 7 days
• Preferred regimen (2): Amoxicillin (1 g twice times daily) for 7 days

FOLLOWED BY

• Preferred regimen (3): Proton pump inhibitor (standard dose twice daily) for 5-7 days
• Preferred regimen (4): Amoxicillin (1 g twice times daily)for 7 days
• Preferred regimen (5): Clarithromycin (500 mg twice daily)for 7 days
• Preferred regimen (6): Nitroimidazole (250 mg four times dailyfor 7 days

• Levofloxacin triple therapy:

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily) for 10-14 days.
• Preferred regimen (2): levofloxacin for 10–14 days
• Preferred regimen (3): Amoxicillin(1 g twice times daily) for 10-14 days

• Fluoroquinolone sequential therapy

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily)for 5 -7 days.
• Preferred regimen (2): Amoxicillin(1 g twice times daily)

FOLLOWED BY

• Preferred regimen (1): Proton pump inhibitor (standard dose twice daily)for 5–7 days
• Preferred regimen (1): Fluoroquinolonefor 5–7 days
• Preferred regimen (1): Nitroimidazolefor 5–7 days

• After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.

The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.

Selection of a first-line H. pylori treatment regimen.

•Key questions? • Is there a penicillin (PCN) allergy? •Previous macrolide (MCL) exposure for any reason ?

•PCN allergy: No •MCL exposure: No

•PCN allergy: No •MCL exposure: Yes

•PCN allergy: Yes •MCL exposure: No

•PCN allergy: Yes •MCL exposure: Yes

Recomended treatment: •Bismuth quadruple •Clarithromycin triple with amoxicillin Other options: •Sequential •HYBRID •Levofloxacin triple •Levofloxacin sequential •LOAD

Recomended treatment: •Bismuth quadruple •Levofloxacin sequential Other options: •Concomitant therapy •Sequential therapy • HYBRID •LOAD

Recomended treatment: •Bismuth quadruple •Clarithromycin triple with metronidazole •Bismuth quadruple

Recomended treatment: •Bismuth quadruple •Clarithromycin triple with metronidazole •Bismuth quadruple

Recommended first-line therapies for H pylori infection:

Regimen	Drug dose	Dosing frequency	Duration(days)	FDA approval
Clarithromycin triple	PPI(standard or double dose Clarithromycin(500mg) Amoxicillin(1gm)or Metronidazole(500mg TID)	BID	14 days	YES†
Bismuth Quadruple	PPI(standard dose) Bismuth subcitrate (120-300mg)or Subsalicylate (300mg) Tetracyclin(500mg) Metronidazole(250-500mg)	BID QID QID TID to QID (500mg)	10-14 days	NO‡
Concomitant	PPI (standard dose) Clarithromycin (500mg) Amoxicillin(1gm) Nitroimidazole(500mg)c	BID	10 -14 days	NO
Sequential	PPI(standard dose)+Amoxicillin(1gm) PPI,Clarithromycin(500mg)+Nitroimidazole(500mg)c	BID BID	5-7 days 5-7 days	NO
Hybrid	PPI(standard)+Amoxicillin(1gm) PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg)c	BID BID	7 days 7 days	NO
Levofloxacin triple	PPI(standard dose) Levofloxacin(500mg) Amoxicillin(1gm)	BID QID BID	10-14 days	NO
Levofloxacin sequential	PPI(standard or double dose)+Amoxicillin(1 gm) PPI,Amoxicillin,Levofloxacin(500mg QD),Nitroimidazole(500mg)c	BID BID	5-7 days	NO
LOAD	Levofloxacin(250mg) PPI(double dose) Nitazoxanide(500mg)c Doxycycline(100mg)	QD QD BID QD	7-10 days	NO
	†: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval, PPI, Clarithromycin, Metronidazole are not an FDA approved treatment regimen. ‡: PPI, Bismuth, Tetracycline, and metronidazole prescribed separately are not an FDA approved treatment regimen. However, Pylera, a combination product containing Bismuth subcitrate, Tetracycline, Metronidazole combination with PPI for 10 days is an FDA approved regimen. BID, twice daily; FDA, Food and Drug Administration; PPI, proton pump inhibitor; TID, three times daily; QD, once daily; QID, four times daily. c:Metronidazole or Tinidazole|} Persistent Helicobacter Pylori infection With declining success rates for H. pylori eradication therapy, many patients will be persistently infected after treatment and will therefore remain at risk for the complications of H. pylori-related disease, such as peptic ulceration and gastric malignancy, testing to prove eradication should be performed using a urea breath test, fecal antigen test or biopsy-based testing at least 4 weeks after the completion of antibiotic therapy and after PPI therapy has been withheld for 1–2 weeks.In patients with persistent H. pylori infection, every effort should be made to avoid antibiotics that have been previously taken by the patient.                                   Persistent Helicobacter Pylori infection                                                                                                                                   Patient recieved clarithromycin triple therapy                               Patient received Bismuth quadriple therapy                                                                                                                                                           •No previous Quinolone exposure •No PCN allergy Recomended treatment: •Bismuth quadruple •Levofloxacin •Rifabutin triple •High dose dual   •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •Bismuth quadruple therapy •Rifabutin triple •High dose dual       •No previous Quinolone exposure •PCN Allergy Recomended treatment: •Bismuth quadruple   •Previous Quinolone exposure •PCN Allergy Recomended treatment: •Bismuth quadruple   •No previous Quinolone exposure •No PCN allergy Recomended treatment: •Levofloxacin triple concomitant •Rifabutin triple •High dose triple   •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •Concomitant Rifabutin triple •High dose dual       •No previous Quinolone exposure •PCN Allergy Recomended treatment: •PPI,Clarithromycin ,Metronidazole •PPI,Levofloxacin, Metronidazole   •Previous Quinolone exposure •No PCN Allergy Recomended treatment: •PPI,Clarithromycin, Metronidazole •Bismuth quadruple   Salvage treatment After the failure of first-line therapy, such patients should be considered for referral for salvage treatment. Salvage therapies for Helicobacter pylori infection Regimen Drugs(doses) Dosing frequency Duration(days) FDA approval Bismuth quadruple PPI(standard dose) Bismuth subciitrate(120-300mg or sub salicylate(300mg) Tetracycline(500mg) Metronidazole(500mg) BID QID QID TID or QID 14 NO(a) Levofloxacin triple PPI(standard dose) Levofloxacin (500mg) Amoxicillin(1gm) BID QD BID 14 NO Concomitant PPI(standard dose) Clarithromycin(500mg) Amoxicillin(1gm) Nitroimidazole(500mg) BID BID BID BID or TID 10-14 NO Rifabutin triple PPI(standard dose) Rifabutin(300mg) Amoxicillin(1gm) BID QD BID 10 NO High-dose dual PPI(standard to double dose) Amoxicillin(1gm TID or 750mg QID) TID or QID TID or QID 14 NO (a)PPI,Bismuth,tetracyclin and metronidazole prescribed separately is not an FDA-approved treatment regimen.However,Pylera,a combination product containing bimuth subcitrate,tetracyclin and metronidazole combined with a PPI for 10 days is an FDA-approved treatment regimen. BID, twice daily; FDA, Food and Drug Administration; PPI, proton pump inhibitor; TID, three times daily; QD, once daily; QID, four times daily. Medical therapy for Non Helicobacter pylori associated Peptic ulcer disease: Active Ulcer Drug Dose H2- receptor Antagonist Cimetidine 800 mg Ranitidine/nizatidine 300 mg Famotidine 40 mg Once daily (at night) Proton pump inhibitors Omeprazole 20 mg Lansoprazole 30 mg Rabeprazole 20 mg Pantoprazole 40 mg Once daily (empty stomach) Maintenance therapy H2-receptor antagonists Cimetidine 400 mg Ranitidine/nizatidine 150 mg Famotidine 20 mg Once daily (at night) Proton pump inhibitors Omeprazole 20 mg Lansoprazole 30 mg Rabeprazole 20 mg Pantoprazole 40 mg Once daily (empty stomach) Prevention of NSAID-induced ulcers Drug Dose Misoprostol 200 μg 3 times/day Proton pump inhibitors Omeprazole 20 mg Lansoprazole 30 mg Rabeprazole 20 mg Pantoprazole 40 mg Once daily (empty stomach) Contraindicated Medications Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications: Ketorolac tromethamine Mefenamic acid Ticlopidine Prasugrel Reserpine Streptokinase Vorapaxar Guidelines and Resources American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia. American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia. American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis. American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection. References