I. Pathophysiology: Helicobacter Pylori

  1. Spiral-shaped Gram Negative Bacteria
  2. Colonizes gastric mucosa or epithelial lining

II. Associated conditions

  1. Dyspepsia
  2. Peptic Ulcer Disease
    1. Duodenal Ulcers: 95% related to H. pylori
    2. Gastric Ulcers: 80% related to H. pylori
  3. Stomach Cancer (epithelial or lymphoid)
    1. IARC considers H. pylori a Group I Carcinogen

III. Symptoms (Asymptomatic in 90% of cases)

IV. Differential Diagnosis

VI. Management: General

  1. Do not indiscriminately test and treat H. pylori
  2. Resistance is increasing markedly
    1. Metronidazole resistance is very common
      1. Resistance overcome by the following measures
        1. Increase acid suppression
        2. Increase Metronidazole dose
        3. Increase therapy duration
    2. Clarithromycin resistance is growing (8-12%)
      1. Resistance can not be overcome
  3. Benefits of treating H. pylori
    1. Significantly drops ulcer recurrence, rebleeding risk
    2. Improves symptoms in Nonulcer Dyspepsia (variable)
    3. Unclear evidence for gastric Cancer Prevention
    4. No evidence for benefit in GERD
  4. Test for H. pylori before treatment
    1. See Helicobacter pylori Noninvasive Testing
  5. Test after treatment if persistant symptoms
    1. Urea Breath Test
    2. H. pylori Stool Antigen (HpSA)
    3. Endoscopic Biopsy for H. pylori
  6. Protocol pearls
    1. Treatment duration: usually 7 to 14 days
    2. Use at least 3 agents (do not use 2 agent regimens)
    3. If failed therapy - see resistant cases below

VII. Protocols: Preferred protocols for adults

  1. Quadruple Therapy (up to 98% efficacy)
    1. Background
      1. Gold standard for Helicobacter Pylori due to highest efficacy, lowest resistance rates and lowest cost
      2. Compliance is difficult due to four time daily dosing
      3. Bismuth causes Constipation and black discoloration of mouth and stools
    2. Components: Use all four for 14 days (extended use of the Proton Pump Inhibitor)
      1. Metronidazole (Flagyl) 250 mg orally four times daily for 14 days
      2. Tetracycline 500 mg orally four times daily for 14 days
        1. No evidence that Doxycycline has equivalent efficacy against Helicobacter Pylori
      3. Bismuth subcitrate (Pepto-Bismol) 525 mg orally four times daily for 14 days
      4. Omeprazole (Prilosec) 20 mg orally twice daily (continue for 6 weeks)
        1. Ranitidine (Zantac) 300 mg orally daily for 6 weeks may be substituted
    3. Combination Packs
      1. Use Omeprazole (or other PPI) with either Helidac or Pylera, which include Metronidazole, Tetracycline and Bismuth
  2. Concomitant Therapy (Triple Therapy with Metronidazole)
    1. Background
      1. Replaces the older triple therapy or LAC protocol (Lasoprazole-Amoxicillin-Clarithromycin)
        1. Addition of Metronidazole signifcantly improves efficacy
      2. More expensive than the quadruple therapy (due to Clarithromycin cost)
      3. Patients may prefer this protocol to quadruple therapy
        1. Better tolerated (no bismuth associated Black Tongue, stools, or Constipation)
        2. Better compliance (twice daily instead of four times daily)
    2. Components: Use all four for 14 days (extended use of the Proton Pump Inhibitor)
      1. Lansoprazole (Prevacid) 30 mg orally twice daily for up to 6 weeks
        1. May substitute Omeprazole (Prilosec) 20 mg orally twice daily
      2. Amoxicillin 1000 mg orally twice daily for 14 days
      3. Clarithromycin (Biaxin) 500 mg orally twice daily for 14 days
        1. Do not substitute other Macrolides
        2. Azithromycin and Erythromycin do not have adequate Helicobacter Pylori coverage
      4. Metronidazole (Flagyl) 500 mg orally twice daily for 14 days

VIII. Protocols: Adults Resistant Cases

  1. General for failed therapy
    1. Step Up to 4-5 agent therapy without Metronidazole
    2. Consider adding Rifabutin (Mycobutin)
      1. Qasim (2005) Aliment Pharmacol Ther 21:91-6 [PubMed] (or open in [QxMD Read])
  2. Quadruple therapy
    1. See Quadruple therapy above under adults long

IX. Protocols: Children

  1. Omeprazole 1 mg/kg/day divided twice daily (max: 20 mg orally twice daily) and
  2. Take the following 3 antibiotics for 14 days (same as concomitant therapy above)
    1. Amoxicillin 50 mg/kg/day divided twice daily (max: 1000 mg twice daily)
    2. Clarithromycin 15mg/kg/day div bid (max: 500 mg twice daily)
    3. Metronidazole 20 mg/kg/day div bid (Max: 500 mg twice daily)
  3. References
    1. Gold (2000) J Pediatr Gastroenterol Nutr 31:490-7 [PubMed] (or open in [QxMD Read])

X. Management: Consider maintenance antisecretory therapy

  1. Maintenance management: 50% of treatment dose
  2. Indicated in
    1. Complicated Peptic Ulcer Disease
    2. Elderly or frail

Images: Related links to external sites (from Google)

Ontology: Anti-Ulcer Agents (C0003216)

Definition (NCI) Natural or synthetic Anti-ulcer Agents relieve and reduce the symptoms of ulcers in the stomach and upper small intestine, systemically and locally, by reducing gastric secretion (proton pump inhibitors), neutralizing hyperacidity (alkalinizing agents), or improving healing and protecting the mucosa (sucralfate). Recurrent gastric and duodenal ulcers caused by Helicobacter pylori infections are treated with antibiotic therapy.
Definition (CSP) class of agents, exclusive of the antibacterial agents, used to treat ulcers in the stomach and the upper part of the small intestine.
Definition (MSH) Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief.
Concepts Pharmacologic Substance (T121)
MSH D000897
English Agents, Anti-Ulcer, Anti Ulcer Agents, Anti-Ulcer Agents, antiulcer drug, Anti Ulcer Drugs, Anti-Ulcer Drugs, Drugs, Anti-Ulcer, ANTIULCER AGENTS, anti-ulcer agents, antiulcer agents, [GA300] ANTIULCER AGENTS, anti ulcer agents, anti ulcer drug, antiulcer drugs, anti-ulcer drugs, antiulcer agent, Anti-ulcer Agent
Portuguese Agentes Antiulcerosos, Antiulcerosos
French Agents antiulcéreux, Médicaments antiulcéreux, Anti-ulcéreux, Antiulcéreux
Swedish Magsårsmedel
Czech protivředové látky
Finnish Ulkuslääkkeet
Italian Farmaci antiulcera, Antiulcera
Polish Leki przeciwwrzodowe
Japanese 消化性潰瘍治療剤, 潰瘍剤, 抗潰瘍剤, 抗潰瘍薬, 消化性潰瘍治療薬, 潰瘍治療薬, 抗消化性潰瘍薬, 抗潰瘍効果, 潰瘍治療剤
German Antiulkusmittel, Ulkusmittel
Spanish Agentes Antiulcerosos

Ontology: Helicobacter pylori (C0079488)

Definition (NCI) Any bacterial organism that can be assigned to the species Helicobacter pylori.
Definition (NCI) A type of bacterium that causes inflammation and ulcers in the stomach or small intestine. People with Helicobacter pylori infections may be more likely to develop cancer in the stomach, including MALT (mucosa-associated lymphoid tissue) lymphoma.
Definition (MSH) A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus CAMPYLOBACTER, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus HELICOBACTER. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405).
Definition (NCI) Bacteria that cause stomach inflammation (gastritis) and ulcers in the stomach. This bacteria is the most common cause of ulcers worldwide. It is often referred to as H. pylori. H. pylori infection is usually acquired from contaminated food and water and through person to person spread. The infection is common in crowded living conditions with poor sanitation. In countries with poor sanitation, 90% of the adult population can be infected. In the U.S., 30% of the adult population is infected. One out of six patients with H. pylori infection develops ulcers of the duodenum or the stomach. This bacteria is also believed to be associated with stomach cancer and a rare type of lymph gland tumor called gastric MALT lymphoma. Infected persons usually carry the infection indefinitely, unless treated with medications to eradicate the bacteria. (MedicineNet.com)
Concepts Bacterium (T007)
MSH D016480
SnomedCT 18066003, 80774000, 123131000
English Campylobacter pylori, Helicobacter pylori, Campylobacter pylori pylori, Helicobacter nemestrinae, Helicobacter nemestrinae (organism), Helicobacter pylori (Marshall et al. 1985) Goodwin et al. 1989, Campylobacter pylori Marshall et al. 1985 corrig. Marshall and Goodwin 1987, Campylobacter pylori subsp. pylori Marshall et al. 1985, Campylobacter pyloridis Marshall et al.1985, Campylobacter pylori corrig. Marshall et al. 1985 emend. Fox et al. 1989, Campylobacter pylori corrig. Marshall et al. 1985 emend. Fox et al. 1988, Helicobacter nemestrinae Bronsdon et al. 1991, HELICOBACTER PYLORI, CAMPYLOBACTER PYLORI, H. PYLORI, h pylori, helicobacter pylori bacteria, campylobacter pylori, h. pylori, helicobacter pylori, helicobacter pylori organism, Helicobacter Pylori (diagnosis), Campylobacter pylori subsp. pylori, Campylobacter pylori subsp pylori, Campylobacter pyloridis, H. pylori, Hp - Helicobacter pylori, Helicobacter pylori (organism), Helicobacter pylori -RETIRED-
Swedish Helicobacter pylori
Spanish Helicobacter nemestrinae (organismo), Campylobacter pylori, Campylobacter pyloridis, Helicobacter nemestrinae, H. pylori, Campylobacter pylori, subespecie pylori, Helicobacter pylori (concepto no activo), Helicobacter pylori (organismo), Helicobacter pylori
Czech Helicobacter pylori, Campylobacter pylori
Finnish Helicobacter pylori
Japanese ヘリコバクター・ピロリ, ヘリコバクターピロリ, ヘリコバクタ・ピロリ
Italian Campylobacter pylori, Helicobacter Pylori (diagnosi), Helicobacter pylori
Polish Campylobacter pylori, Helicobacter pylori
French Helicobacter pylori (diagnostic), Campylobacter pylori, Helicobacter pylori
German Campylobacter pylori, Helicobacter pylori
Dutch Campylobacter pylori, Helicobacter pylori
Portuguese Campylobacter pylori, Helicobacter pylori

Ontology: Helicobacter-associated gastritis (C0343378)

Concepts Disease or Syndrome (T047)
SnomedCT 155716003, 196741008, 89538001, 186143000
Italian Gastrite da Helicobacter, Gastrite da Helicobacter pylori
Dutch Helicobacter pylori-gastritis, Helicobacter-gastritis
French Gastrite à helicobacter pylori, Gastrite à Hélicobacter
German Helicobacter pylori-Gastritis, Helicobacter-Gastritis
Portuguese Gastrite a Helicobacter pylori, Gastrite por helicobactéria
Japanese ヘリコバクター性胃炎, ヘリコバクター・ピロリ性胃炎, ヘリコバクターピロリセイイエン, ヘリコバクターセイイエン
English Helicobacter gastritis, gastritis associated with Helicobacter pylori (diagnosis), gastritis associated with Helicobacter pylori, gastritis due to H. pylori, Helicobacter gastritis (disorder), Helico pylori-assoc gastritis, gastritis helicobacter pylori, helicobacter gastritis, helicobacter pylori gastritis, Helicobacter pylori gastritis, Helicobacter-associated gastritis, Helicobacter pylori-associated gastritis, Helicobacter-associated gastritis (disorder), Helicobacter Gastritis, Helicobacter Pylori-Associated Gastritis
Spanish Helicobacter gastritis, Gastritis por Helicobacter pylori, Gastritis por Helicobacter, gastritis asociada con Helicobacter (trastorno), gastritis asociada con Helicobacter
Czech Helikobakterová gastroenteritida, Gastritida vyvolaná Helicobacter pylori
Hungarian Helicobacter gastritis, Helicobacter pylori gastritis

Ontology: Helidac Therapy Pack (C0977365)

Concepts Drug Delivery Device (T203)
English HELIDAC THERAPY KIT 525 MG/250 MG/50 MG, Helidac Therapy Kit, Helidac Therapy Pack, {112 (bismuth subsalicylate 262 MG Chewable Tablet) / 56 (Metronidazole 250 MG Oral Tablet) / 56 (Tetracycline 500 MG Oral Capsule) } Pack [Helidac Therapy], Helidac, 262.4 mg-250 mg-500 mg oral kit, TETRACYCLINE HYDROCHLORIDE 500 MG ORAL CAPSULE [HELIDAC], BISMUTH SUBSALICYLATE 262 MG ORAL TABLET, CHEWABLE [HELIDAC], HELIDAC Therapy KIT, HELIDAC KIT 262 MG/250 MG;MG, HELIDAC THERAPY PACK [VA Product], HELIDAC THERAPY KIT 262.4 MG/250 MG/ MG, HELIDAC THERAPY KIT 262 MG/250 MG;MG, {112 (bismuth subsalicylate 262 MG Chewable Tablet) / 56 (metroNIDAZOLE 250 MG Oral Tablet) / 56 (Tetracycline 500 MG Oral Capsule) } Pack [Helidac Therapy], Bismuth Subsalicylate/Metronidazole/Tetracycline Hydrochloride 262.4 MG-250 MG-500 MG Oral Kit [HELIDAC THERAPY], HELIDAC THERAPY PACK

Ontology: bismuth subcitrate 140 MG / Metronidazole 125 MG / Tetracycline 125 MG Oral Capsule (C1948529)

Concepts Clinical Drug (T200)
English BISMUTH/METRONID/TETRACYCLINE 140 mg-125 mg-125 mg ORAL CAPSULE (HARD, SOFT, ETC.), COLLOIDAL BISMUTH SUBCITRATE/METRONIDAZOLE/TETRACYCLINE HCL 140 mg-125 mg-125 mg ORAL CAPSULE (HARD, SOFT, ETC.), COLLOIDAL BISMUTH SUBCITRATE/METRONIDAZOLE/TETRACYCLINE HCL@140 mg-125 mg-125 mg@ORAL@CAPSULE (HARD, SOFT, ETC.), bismuth subcitrate potassium/metronidazo/TCN 140 mg-125 mg-125 mg oral capsule, BISMUTH 140MG/METRONIDAZOLE 125MG/TETRACYCLINE 125MG CAP,ORAL, bismuth subcitrate 140 MG / Metronidazole 125 MG / Tetracycline 125 MG Oral Capsule, PYLERA ORAL CAP, BISMUTH 140MG/METRONIDAZOLE 125MG/TETRACYCLINE 125MG CAP,ORAL [VA Product], Bismuth Subcitrate Potassium, Metronidazole, Tetracycline 140-125-125mg Oral capsule, bismuth subcitrate 140 MG / metroNIDAZOLE 125 MG / Tetracycline 125 MG Oral Capsule, Bismuth Subcitrate Potassium/Metronidazole/Tetracycline Hydrochloride 140 MG-125 MG-125 MG Oral Capsule