This Professional Resource gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER October 2016 ~ Resource #321032 Helicobacter pylori: From Diagnosis to Eradication Though prevalence of H. pylori is decreasing in some parts of the world, it remains a common infection for many patients. 1,2 H. pylori has been implicated in the development of certain gastrointestinal problems (e.g., ulcers, cancer, gastric mucosa associated lymphoid tissue lymphomas). 1,2 Not all patients should be tested for H. pylori. However, testing should only be done for patients that prescribers will treat if results are positive. 2 Antibiotic resistance has reduced treatment success rates with many traditional three-drug regimens. 1,2 Longer durations of therapy (e.g., 14 days) are now recommended for successful eradication. 1,2 The chart below reviews common questions associated with H. pylori infection, including who and how to test and recommended treatment regimens for ADULTS. Abbreviations: BID = twice daily; MALT = mucosa associated lymphoid tissue; PPI = proton pump inhibitor; RUT = rapid urease test; TID = three times daily; QD = once daily; QID = four times daily; UBT = urea breath test. PPI Equivalent Doses for the regimens discussed below: 1,2 Dexlansoprazole 30 to 60 mg = Esomeprazole 20 to 40 mg = Omeprazole 20 mg = Lansoprazole 30 mg = Pantoprazole 40 mg = Rabeprazole 20 mg Who should be tested for H. pylori? Recommend testing for H. pylori in patients with the following: 2 o Active peptic ulcer disease o After resection of early gastric cancer o Gastric MALT lymphoma o History of documented peptic ulcer disease o Uninvestigated dyspepsia (if local H. pylori prevalence is high) Consider testing for H. pylori in patients with the following: 2 o Gastroesophageal reflux disease o High risk for gastric cancer o Nonulcer dyspepsia o Unexplained iron deficiency anemia o Use of nonsteroidal antiinflammatory drugs Which test is should be used for patients undergoing endoscopy? Rapid Urease Test (RUT) 2 o Advantages: inexpensive, very good sensitivity, rapid results (usually within one to 24 hours) o Disadvantages: reduced sensitivity post-treatment o Recommend if no recent use of PPI (past one to two weeks) or bismuth (past four weeks).
(Professional Resource #321032: Page 2 of 5) Tests for patients undergoing endoscopy, continued Which test should be used for patients NOT undergoing endoscopy? Which H. pylori regimens are recommended first-line? Histology 2 o Advantages: excellent sensitivity and specificity o Disadvantages: expensive, requires significant personnel training o Recommend if recent use of PPI, antibiotics, or bismuth. Culture 2 o Advantages: excellent specificity, provides antimicrobial sensitivities o Disadvantages: expensive, difficult to perform, marginal sensitivity o Avoid routinely recommending due to cost and limited availability. Recommend with endoscopies after treatment failures to assess antibiotic sensitivity. 5 Polymerase Chain Reaction 2 o Advantages: excellent specificity and sensitivity, provides antimicrobial sensitivities o Disadvantages: lack of standardization across locations, not widely available. o Avoid routinely recommending, used primarily in research. Antibody Testing (detects IgG antibodies in serum, whole blood, or urine) 2 o Advantages: inexpensive, rapid results o Disadvantages: Less accurate post-treatment, avoid in patients with previous H. pylori treatment. UBT 2 o Advantages: useful before and after treatment o Disadvantages: inconsistent availability and reimbursement o Recommend if testing for eradication of H. pylori. Fecal Antigen Test 2 o Advantages: useful before and after treatment o Disadvantages: requires stool collection, less validated than UBT for post-treatment o Tests in the laboratory using monoclonal antibody reagents are more accurate than rapid in-office tests using polyclonal antibodies. 5 Recommend 14 days of therapy with one of the following preferred options for most patients: 1 o PPI + Bismuth + Metronidazole + Tetracycline (PBMT) Bismuth subsalicylate 524 mg QID Metronidazole 500 mg TID to QID Tetracycline 500 mg QID
(Professional Resource #321032: Page 3 of 5) First-line H. pylori regimens, continued o PPI + Amoxicillin + Metronidazole + Clarithromycin (PAMC)* *Consider using Prevpac (U.S.) or Hp-PAC (Canada), which contains a PPI (lansoprazole), amoxicillin, and clarithromycin, concomitantly with metronidazole depending on cost. What are the alternatives to the firstline recommendations? Consider 14 days of therapy with one of the following regimens in areas with known clarithromycin resistance of <15% or proven high local eradication rates of >85%: 1 o PPI + Amoxicillin + Clarithromycin (PAC) o PPI + Metronidazole + Clarithromycin (PMC) o PPI + Amoxicillin + Metronidazole (PAM) in areas with demonstrated success rates. Which H. pylori regimens are appropriate after treatment failure? Consider the following AFTER treatment failure with one of the first-line (or alternative first-line) regimens: 1 o Avoid retreating with clarithromycin-containing regimens after a clarithromycin failure. Recommend treating with 14 days with PBMT or a levofloxacin-containing regimen (e.g., PPI + Amoxicillin + Levofloxacin [PAL]). PPI: omeprazole 20 mg BID or an equivalent dose of an alternate PPI Amoxicillin 1000 mg BID Levofloxacin 500 mg QD
(Professional Resource #321032: Page 4 of 5) Options after treatment failure, continued What should NOT be recommended as a treatment option for H. pylori? Should probiotics be recommended to improve efficacy or tolerability? Who should be tested to confirm eradication of H. pylori? Adding bismuth to PAL or increasing the PPI and/or metronidazole dose when retreating with PBMT may improve eradication but data are limited supporting these strategies. Avoid PAL if associated with a prior failure or in patients with prior quinolone exposure. o Save treatment with ten days of a rifabutin-containing regimen (e.g., PPI + Amoxicillin + Rifabutin [PAR]) for patients with multiple (e.g., >3) treatment failures. Rifabutin 150 mg BID Sequential non-bismuth quadruple therapy (e.g., PPI + Amoxicillin for five days, followed by PMC for five days) o Not recommended as a first-line option in published U.S. or Canadian guidelines. 1,2 Not recommended as an alternative option in the updated Canadian guidelines. 1 Current U.S. guidelines under revision. Previous U.S. guidelines (2007) noted additional data needed before able to recommend. 2 Less than 14 days of any regimen, other than PAR (10 days is appropriate after failure of >3 regimens). 1 Doxycycline-based regimens 1 Levofloxacin-based quadruple therapy 1 H2-blockers as alternatives to PPIs 1 Single antibiotic or two-drug (e.g., high dose PPI + an antibiotic) regimens 1 Avoid recommending probiotics to improve H. pylori eradication. 1 o Data are inconsistent and more trials, including use with quadruple therapy, are needed. 1,3 o Product ingredient combinations and concentrations vary significantly. 1 o Increases cost and complexity of treatment. 1 Don t routinely recommend, but don t discourage use to improve treatment tolerability. 1 o May improve diarrhea associated with treatment regimens. 1,3 Patients with an H. pylori-associated ulcer. Patients with persistent dyspepsia after H. pylori treatment. Patients with H. pylori-associated MALT lymphoma. Patients with a history of resection associated with gastric cancer. For the most accurate results use the UBT or fecal antigen test, at least four weeks after treatment. 2,4
(Professional Resource #321032: Page 5 of 5) Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this professional resource: Beth Bryant, Pharm.D., BCPS, Assistant Editor References 1. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology 2016;151:51-69. 2. Chey WD, Wong BC; Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007;102:1808-25. 3. McFarland LV, Huang Y, Wang L, Malfertheiner P. Systematic review and meta-analysis: multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events. United European Gastroenterol J 2016;4:546-61. 4. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut 2015;64:1353-67. 5. Malfertheiner P, Megraud F, O Morain CA, et al. Management of Helicobacter pylori infection the Maastricht IV/Florence consensus report. Gut 2012;61:646-64. Cite this document as follows: Professional Resource, Helicobacter pylori: From Diagnosis to Eradication. Pharmacist s Letter/Prescriber s Letter. October 2016. Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2016 by Therapeutic Research Center Subscribers to the Letter can get professional resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com