Tag Archives: clarithromycin

Understanding Resistance to Helicobacter pylori

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An editorial (by Ben Gold -congratulations!) helps sort out the potential advantages of gene based testing for Helicobacter pylori in a commentary on a recent publication (JPGN 2014;  59: 6-9).

In the study, the authors used formalin=fixed biopsies in 38 H pylori--infected gastric biopsies.  These specimens were examined for 23S rRNA mutations associated with resistance to clarithromycin.  Overall, the authors (from Dallas, TX) noted H pylori in 4.5% of their biopsies.  The majority of these children, treated between 2010-2012, were given clarithromycin, amoxicillin, and a proton pump inhibitor (n=25).  Due to clarithromycin resistance, this is no longer considered a first-line treatment in the absence of clarithromycin susceptibility testing according to NASPGHAN guidelines (published in 2011).

The authors noted a cure rate of 62.5%, likely due to the use of clarithromycin-based triple therapy.  In addition, Dr. Gold notes that the authors identified a very high rate of clarithromycin resistance (50%): “greater than that reported by any of the previously published national surveys or single-center studies in the United States, Europe, or Japan.”

Take-home point from Dr. Gold: “Because the common mutations responsible for H pylori resistance to the other major antimicrobials used for eradication…have been described, the assay developed by Mittui et al could be modified to include a panel of antibiotics…to optimize therapy.”

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High Rates of Helicobacter Pylori Resistance

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While the development of antibacterial resistance has broad implications, in gastroenterology patients specific problems have emerged with Helicobacter pylori (H pylori) and this has led to changes in first-line therapy( ).  More data on the treatment resistant H pylori has been published (JPGN 2013; 56: 645-48).

77 consecutive strains of H pylori  from Brazilian children and adolescents were isolated from gastric biopsies and analyzed; this study took place between 2008-2009 and the mean age was 11.1 years.  In 71 strains, there were no previous attempts at eradication.

Results:

  • 40% of strains were resistant to metronidazole
  • 19.5% of strains were resistant to clarithromycin
  • 10.4% of strains were resistant to amoxicillin
  • All strains were susceptible to furazolidone and tetracycline
  • 14/77 (18.2%) patients had multiple resistances

Take-home point: Resistance to antibiotics is altering our approach to H pylori therapy.  Antibiotic susceptibility testing may be needed to improve antibiotic selection and eradication rates.

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Helicobacter pylori –useful advice

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Helicobacter pylori (H pylori) infections remain an important cause of gastritis, ulcers, and adenocarcinoma of the stomach.  One new approach in treatment has been the use of sequential therapy.  More data is now available on the effectiveness of this approach and choice of antibiotics (Gastroenterology 2012; 143: 55-61 & editorial 10-12).

In the study, a 10-day sequential regimen (SR) was compared with a 5-day concomitant regimen (CR).

  • CR group (n=90): esomeprazole 40 mg BID, amoxicillin 1 g BID, levofloxacin 500 mg BID, tinidazole 500 mg BID.  Eradication rate (intention-to-treat): 92%
  • SR group (n-90): esomeprazole 40 mg BID, amoxicillin 1 g BID for 5 days, then esomeprazole 40 mg BID, levofloxacin 500 mg BID, tinidazole 500 mg BID for 5 days. Eradication rate (intention-to-treat): 93%
  • Both groups had good results in part due to low resistance rates

Useful advice on this study from the editorial:

  • ‘We prefer concomitant therapy because it is not complex and it may retain its effectiveness at a slightly higher level of resistance compared with sequential therapy.”  Authors prefer 4-drug non-bismuth-containing concomitant treatment.
  • With bismuth therapy (eg. bismuth-metronidazole-tetracycline-PPI), authors prefer a 14 day course.  10-day treatment may be effective when metronidazole resistance is considered unlikely.
  • “Clarithromycin should be abandoned as an empiric regimen” due to resistance in U.S.
  • Fluoroquinolone resistance is increasing rapidly and “prior use virtually ensures resistance.”  Suggested use of fluoroquinolone therapy among adults would be as a rescue therapy (failed 2 different therapies), using dosing regimen as noted in cited study, and in patient without history of prior fluoroquinolone use (&/or proof on susceptibility testing)
What about treatment in kids?
In pediatrics, guidelines for treatment have been recently updated (JPGN 2011; 53: 230-43). (Benjamin Gold, MD -one of my partners is one of the authors and was the lead author of the first guidelines published in 2000.)  NASPGHAN guidelines. PDF of powerpoint slides: H. pylori infection in children: ESPGHAN/ NASPGHAN guidelines … & pdf of text: Evidence-based guidelines from ESPGHAN and NASPGHAN for …
Recommendations for first line treatment are a triple-based therapy with PPI and two antibiotics (eg. amoxicillin and metronidazole).  Alternatives, include bismuth plus two antibiotics, or sequential therapy.  Use of clarithromycin is recommended only after susceptibility testing.

Additional references:

  • -Gut 2010; 59: 1143-53.  Changing treatment recommendations for Helicobacter pylori in the face of resistance.
  • -Am J Gastroenterol 2007;  102: 1808-1825. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection.  Doxycycline can be used in place of tetracycline
  • -Gastroenterol 2007; 133: 985. Review. Good article for resistant infections.
  • -Gastroenterol 2005; 129:1414-19.  Sequential Rx (amox + PPI x 5 days, then biaxin, tinidazole, PPI for 5 days) had 97% success.