Peptic ulcer medical therapy
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Peptic ulcer Microchapters |
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Diagnosis |
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Treatment |
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Surgery |
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Case Studies |
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2017 ACG Guidelines for Peptic Ulcer Disease |
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Guidelines for the Indications to Test for, and to Treat, H. pylori Infection |
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Guidlines for factors that predict the successful eradication when treating H. pylori infection |
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Guidelines to document H. pylori antimicrobial resistance in the North America |
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Guidelines for evaluation and testing of H. pylori antibiotic resistance |
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Guidelines for when to test for treatment success after H. pylori eradication therapy |
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Guidelines for penicillin allergy in patients with H. pylori infection |
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Peptic ulcer medical therapy On the Web |
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American Roentgen Ray Society Images of Peptic ulcer medical therapy |
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Risk calculators and risk factors for Peptic ulcer medical therapy |
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.
Treatment Guidelines
Treatment is based on the cause of peptic ulcer.It is divided into 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[1][2] :
- 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[3][4].
In Clarithromycin resistance following therapies are used
- Bismuth quadruple therapy consisting of a PPI, bismuth, tetracycline, and a nitroimidazole for 10–14 days is a recommended first-line treatment option.It is particularly attractive in patients with any previous macrolide exposure or clarithromycin resistance is known to be high or who are allergic to penicillin. bismuth quadruple therapy should be strongly considered as the initial treatment choice.[5]
- Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin and a nitroimidazole for 10–14 days is a recommended first-line treatment option[6][7].
- Sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI, clarithromycin, and a nitroimidazole for 5–7 days is a suggested first-line treatment option[8][9][10].
- Hybrid therapy consisting of a PPI and amoxicillin for 7 days followed by a PPI, amoxicillin, clarithromycin and a nitroimidazole for 7 days is a suggested first-line treatment option.
- Levofloxacin triple therapy consisting of a PPI, levofloxacin, and amoxicillin for 10–14 days is a suggested first-line treatment option[11][8][12][13]
- Fluoroquinolone sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI, fluoroquinolone, and nitroimidazole for 5–7 days is a suggested first-line treatment option.
- The use of high-dose (twice a day) proton pump inhibitor (PPI) increases the efficacy of triple therapy.
- In areas of low clarithromycin resistance, clarithromycin-containing treatments (PCA or PCM) are recommended for first-line empirical treatment. Bismuth-containing quadruple treatment is also an alternative.
- In areas of high clarithromycin resistance, bismuth-containing quadruple treatment is recommended for first-line empirical treatment. If this regimen is not available, sequential treatment is recommended.
- Extending the duration of triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
- After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple treatment or levofloxacin-containing triple therapy (PLA) is recommended.
- 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.[14]
| •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 | ||||||||||||||||||||||||||||||||||
Triple Therapy
- 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 (1):Clarithromycin (500 mg twice daily) for 7–14 days AND
- Preferred regimen (1):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 (1): Clarithromycin (500 mg twice daily) for 7–14 days AND
- Alternative regimen (1): 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 (1): Levofloxacin (500 mg twice daily) for 10 days AND
- Alternative regimen (1): 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
Quadruple Therapy
Bismuth-Containing Quadruple Therapy
- 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
Non–Bismuth-Containing Quadruple Therapy
- Concomitant therapy
- Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
- Alternative regimen (1): Clarithromycin (500 mg twice daily) for 7–14 days AND
- Alternative regimen (1): Amoxicillin (1 g twice daily) for 10 days AND
- Alternative regimen (1): Metronidazole (250 mg four times daily) for 7–14 days
- Sequential therapy
- Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for 5 days AND
- Alternative regimen (1): Amoxicillin (1 g twice times daily) for 5 days
FOLLOWED BY - Alternative regimen (1): Proton pump inhibitor (standard dose twice daily) for another 5 days AND
- Alternative regimen (1): Clarithromycin (500 mg twice daily) for another 5 days AND
- Alternative regimen (1): Tinidazole (500 mg twice daily) for another 5 days
| 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) |
BID | 10 -14 days | NO |
| Sequential | PPI(standard dose)+Amoxicillin(1gm)
PPI,Clarithromycin(500mg)+Nitroimidazole(500mg) |
BID
BID |
5-7 days
5-7 days |
NO |
| Hybrid | PPI(standard)+Amoxicillin(1gm)
PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg) |
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) |
BID
BID |
5-7 days | NO |
| LOAD | Levofloxacin(250mg)
PPI(double dose) Nitazoxanide(500mg) 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. | ||||
| 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
Most patients with a history of penicillin allergy or do not have true penicillin hypersensitivity. After the failure of first-line therapy, such patients should be considered for referral for allergy testing since the vast majority can ultimately be safely given amoxicillin containing salvage regimens.
| Salvage therapies for Helicobacter pylori infection | ||||
|---|---|---|---|---|
| Regimen | Drugs(doses) | Dosing frequency | Duration(days) | FDA approval |
| Bismuth quadruple |
|
BID
QID QID TID or QID |
14 | NO(a) |
| Levofloxacin triple |
|
BID
QD BID |
14 | NO |
| Concomitant |
|
BID
BID BID BID or TID |
10-14 | NO |
| Rifabutin triple |
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BID
QD BID |
10 | NO |
| High-dose dual |
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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
Contraindicated Medications
Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications:
Guidelines and Resources
- American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia.[15]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia.[16]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.[17]
- 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.[18]
- The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection.[19]
References
- ↑ Federico A, Gravina AG, Miranda A, Loguercio C, Romano M (2014). "Eradication of Helicobacter pylori infection: which regimen first?". World J. Gastroenterol. 20 (3): 665–72. doi:10.3748/wjg.v20.i3.665. PMC 3921476. PMID 24574740.
- ↑ Zullo A, Rinaldi V, Winn S, Meddi P, Lionetti R, Hassan C, Ripani C, Tomaselli G, Attili AF (2000). "A new highly effective short-term therapy schedule for Helicobacter pylori eradication". Aliment. Pharmacol. Ther. 14 (6): 715–8. PMID 10848654.
- ↑ Maconi G, Parente F, Russo A, Vago L, Imbesi V, Bianchi Porro G (2001). "Do some patients with Helicobacter pylori infection benefit from an extension to 2 weeks of a proton pump inhibitor-based triple eradication therapy?". Am. J. Gastroenterol. 96 (2): 359–66. doi:10.1111/j.1572-0241.2001.03519.x. PMID 11232676.
- ↑ Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F (2007). "Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication". Ann. Intern. Med. 147 (8): 553–62. PMID 17938394.
- ↑ Venerito M, Krieger T, Ecker T, Leandro G, Malfertheiner P (2013). "Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection". Digestion. 88 (1): 33–45. doi:10.1159/000350719. PMID 23880479.
- ↑ Wu DC, Hsu PI, Wu JY, Opekun AR, Kuo CH, Wu IC, Wang SS, Chen A, Hung WC, Graham DY (2010). "Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection". Clin. Gastroenterol. Hepatol. 8 (1): 36–41.e1. doi:10.1016/j.cgh.2009.09.030. PMC 2838430. PMID 19804842.
- ↑ Chuah SK, Tsay FW, Hsu PI, Wu DC (2011). "A new look at anti-Helicobacter pylori therapy". World J. Gastroenterol. 17 (35): 3971–5. doi:10.3748/wjg.v17.i35.3971. PMC 3199554. PMID 22046084.
- ↑ 8.0 8.1 Gatta L, Vakil N, Leandro G, Di Mario F, Vaira D (2009). "Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children". Am. J. Gastroenterol. 104 (12): 3069–79, quiz 1080. doi:10.1038/ajg.2009.555. PMID 19844205.
- ↑ Vaira D, Zullo A, Vakil N, Gatta L, Ricci C, Perna F, Hassan C, Bernabucci V, Tampieri A, Morini S (2007). "Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial". Ann. Intern. Med. 146 (8): 556–63. PMID 17438314.
- ↑ Gisbert JP, Calvet X, O'Connor A, Mégraud F, O'Morain CA (2010). "Sequential therapy for Helicobacter pylori eradication: a critical review". J. Clin. Gastroenterol. 44 (5): 313–25. doi:10.1097/MCG.0b013e3181c8a1a3. PMID 20054285.
- ↑ Molina-Infante J, Perez-Gallardo B, Fernandez-Bermejo M, Hernandez-Alonso M, Vinagre G, Dueñas C, Mateos-Rodriguez JM, Gonzalez-Garcia G, Abadia EG, Gisbert JP (2010). "Clinical trial: clarithromycin vs. levofloxacin in first-line triple and sequential regimens for Helicobacter pylori eradication". Aliment. Pharmacol. Ther. 31 (10): 1077–84. doi:10.1111/j.1365-2036.2010.04274.x. PMID 20180787.
- ↑ Caselli M, Zullo A, Maconi G, Parente F, Alvisi V, Casetti T, Sorrentino D, Gasbarrini G (2007). ""Cervia II Working Group Report 2006": guidelines on diagnosis and treatment of Helicobacter pylori infection in Italy". Dig Liver Dis. 39 (8): 782–9. doi:10.1016/j.dld.2007.05.016. PMID 17606419.
- ↑ Romano M, Cuomo A, Gravina AG, Miranda A, Iovene MR, Tiso A, Sica M, Rocco A, Salerno R, Marmo R, Federico A, Nardone G (2010). "Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial". Gut. 59 (11): 1465–70. doi:10.1136/gut.2010.215350. PMID 20947881.
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in:
|date=(help) - ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in:
|date=(help) - ↑ Ikenberry, Steven O.; Harrison, M. Edwyn; Lichtenstein, David; Dominitz, Jason A.; Anderson, Michelle A.; Jagannath, Sanjay B.; Banerjee, Subhas; Cash, Brooks D.; Fanelli, Robert D.; Gan, Seng-Ian; Shen, Bo; Van Guilder, Trina; Lee, Kenneth K.; Baron, Todd H.; ASGE STANDARDS OF PRACTICE COMMITTEE (2007-12). "The role of endoscopy in dyspepsia". Gastrointestinal Endoscopy. 66 (6): 1071–1075. doi:10.1016/j.gie.2007.07.007. ISSN 0016-5107. PMID 18028927. Check date values in:
|date=(help) - ↑ ASGE Standards of Practice Committee; Fukami, Norio; Anderson, Michelle A.; Khan, Khalid; Harrison, M. Edwyn; Appalaneni, Vasudhara; Ben-Menachem, Tamir; Decker, G. Anton; Fanelli, Robert D.; Fisher, Laurel; Ikenberry, Steven O.; Jain, Rajeev; Jue, Terry L.; Krinsky, Mary Lee; Maple, John T.; Sharaf, Ravi N.; Dominitz, Jason A. (2011-07). "The role of endoscopy in gastroduodenal obstruction and gastroparesis". Gastrointestinal Endoscopy. 74 (1): 13–21. doi:10.1016/j.gie.2010.12.003. ISSN 1097-6779. PMID 21704805. Check date values in:
|date=(help) - ↑ Bhatt, Deepak L.; Scheiman, James; Abraham, Neena S.; Antman, Elliott M.; Chan, Francis K. L.; Furberg, Curt D.; Johnson, David A.; Mahaffey, Kenneth W.; Quigley, Eamonn M.; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (2008-10-28). "ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents". Circulation. 118 (18): 1894–1909. doi:10.1161/CIRCULATIONAHA.108.191087. ISSN 1524-4539. PMID 18836135.
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in:
|date=(help)