Helicobacter pylori Infection Treatment 

Updated: Oct 27, 2018
  • Author: Joseph Adrian L Buensalido, MD; more...
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Helicobacter pylori Infection Treatment

Regimens for eradication of Helicobacter pylori infection are typically chosen empirically, on the basis of regional bacterial resistance patterns, local recommendations, and drug availability. [1]  Health care providers should ask their patients about any prior antibiotic use or exposure, and take that information into consideration before choosing a treatment regimen. [2]  The following regimens are described below [3] :

  • Triple therapy
  • Nonbismuth quadruple therapy
  • Bismuth-based therapy
  • Levofloxacin-containing therapy
  • Concomitant bismuth and levofloxacin-containing therapy
  • Second-line therapy
  • Rescue or third-line therapy

Triple therapy

Triple therapy for H  pylori infection remains an option for first-line therapy in areas of low (< 15%) clarithromycin resistance [4] and consists of the following:

  1. Proton pump inhibitor (PPI) (eg, omeprazole 20 mg BID, lansoprazole 30 mg BID, esomeprazole 40 mg QD, pantoprazole 40 mg QD, rabeprazole 20 mg BID) [5, 6]  plus

  2. Clarithromycin 500 mg BID [5] (first-line and continues to be recommended in areas where H pylori clarithromycin resistance is less than 15% and in patients without previous macrolide exposure [2] ​) or  metronidazole 500 mg BID [5] (when clarithromycin resistance is increasing) [7, 8]  plus

  3. Amoxicillin 1000 mg BID [5] or  metronidazole 500 mg BID [9] (if not already selected)

Duration

A Cochrane meta-analysis of 55 studies concluded that 14 days is the optimal duration of triple therapy, achieving an H pylori eradication rate of 81.9%, whereas 7 days attains an eradication rate of only 72.9%. [10] In more recent studies, however, the eradication rate with 14-day triple therapy is not significantly different from that with 10-day sequential therapy (amoxicillin and a PPI for 5 days followed by a PPI, clarithromycin and metronidazole for another 5 days) [11]  or 10-day concomitant nonbismuth quadruple therapy. [12]

Nonbismuth quadruple therapy

Nonbismuth quadruple therapy may be given sequentially or concomitantly. [3]

Sequential therapy 

Sequential therapy (a suggested first-line option [2] ) is superior to standard triple therapy, according to two systematic reviews, [13, 14] and consists of the following:

  1. PPI plus amoxicillin for 5-7 days (eg, pantoprazole 40 mg BID and amoxicillin 1 g BID for 7 days [15] ), then

  2. PPI plus 2 other antibiotics for the next 5-7 days; clarithromycin and metronidazole are the antibiotics usually chosen, but levofloxacin-based regimens (see below) [13, 16, 17] and tetracycline-based regimens (eg, pantoprazole 40 mg BID, tetracycline 500 mg QID, and metronidazole 500 mg BID) [15] are superior to 14-day triple therapy, based on a meta-analysis of 21 trials [13]

Eradication rates with different durations of sequential therapy are as follows:

  • 14 days: 90.7-92.5% eradication rates [18, 19]

  • 10 days: 87% eradication rate [6, 5, 18]

Concomitant therapy

Concomitant therapy (an alternative first-line option [2] ) consists of the following (using dosages similar to those in triple therapy; or all drugs BID in one study):

  • PPI plus

  • Amoxicillin plus

  • Clarithromycin (1 g modified-release tablet QD in one study) plus

  • Metronidazole (500 mg TID in one study)

Duration of concomitant therapy is 10-14 days. [20, 21, 6]

Concomitant therapy is better for clarithromycin-resistant strains, [20, 4] and 14 days of concomitant therapy is superior to 14-day triple therapy, with cure rates of ≥90%. [22, 23, 24, 25]

Hybrid therapy

Hybrid therapy is a combination of sequential and concomitant therapy, [3, 26, 27] as follows:

  1. PPI plus amoxicillin for 3 - 7 days (the latter recommended as another suggested first-line option in the 2017 American College of Gastroenterology Guideline [2] ), then

  2. PPI plus amoxicillin plus 2 other antibiotics (usually, clarithromycin and metronidazole) for 7 days

There is evidence that the eradication rates with 10-day, 12-day and 14-day regimens are comparable at 95.0%, 95.1%, and 93.4%, respectively. This suggests that the optimal duration of hybrid therapy is 12 days, since high rates of eradication are still achieved.

Reverse Hybrid

Reverse hybrid therapy is a combination of sequential and concomitant therapy, using the same drugs as hybrid therapy, but in reverse sequence, [27]  as follows:

  1. PPI plus amoxicillin plus 2 other antibiotics (usually, clarithromycin and metronidazole) for 7 days then
  2. PPI plus amoxicillin for 3–7 days

The eradication rate achieved with 12 days of reverse hybrid therapy is similar to that with 12 days of hybrid therapy (95.7% vs. 95.1%, respectively).

Novel concomitant therapy

Novel concomitant therapy consists of the following [28] :

  1. PPI (eg, rabeprazole 20 mg TID) for 10 days plus

  2. Amoxicillin 1 g TID for 10 days (or, if penicillin allergic, bismuth subcitrate 240 mg QID for 10 days) plus

  3. Rifabutin 150 mg BID for 10 days plus

  4. Ciprofloxacin 500 mg BID for 10 days

The regimen with amoxicillin eradicated H  pylori in 95.2% of cases, while the one with bismuth subcitrate achieved an eradication rate of 94.2%.

Bismuth-based therapy

Bismuth-based therapy is an alternative first-line therapy (in areas with high clarithromycin and metronidazole resistance, and in patients with prior macrolide exposure or penicillin-allergic) [4, 2]  or second-line therapy (see below). [3] It consists of the following:

  1. PPI or H2 receptor antagonist (eg, lansoprazole 30 mg BID [12] or ranitidine 150 mg BID [5] ) plus

  2. Bismuth subsalicylate 525 mg QID [5]  (or bismuth tripotassium dicitrate 300 mg QID [12] plus

  3. Metronidazole 250 mg QID [5]  or 500 mg TID [12]  (or levofloxacin) [29] plus

  4. Tetracycline 500 mg QID [5]

Duration is 10-14 days. [5, 30, 6, 12] The eradication rate was 90.4% for 10 days of bismuth quadruple therapy,

while extending therapy to 14 days achieved an eradication rate of 97.1% [30]

Chinese researchers reported that the following regimen provides effective first-line treatment in a population with high antibiotic resistance [31] :

  • Rabeprazole 10 mg BID  plus
  • Bismuth potassium citrate 220 mg BID  plus
  • Amoxicillin 1000 mg BID  plus
  • Clarithromycin 500 mg BID

Duration is 10 days. Rabeprazole and bismuth were given 30 min before the morning and evening meals. Antibiotics were given 30 min after the morning and evening meals. [31]

Researchers in Turkey, however, reported that a 14-day regimen of lansoprazole 30 mg BID, amoxicillin 1000 mg BID, clarithromycin 500 mg BID, bismuth subsalicylate 600 mg BID was not significantly superior to a 7-day regimen (81.4% vs. 80%). [32]

Levofloxacin-containing therapy

This is an alternative first-line regimen [16, 33] and consists of a PPI plus amoxicillin 1 g BID plus levofloxacin 500 mg QD. [5]

Duration options are as follows:

  • 7 days (eradication rates of up to 80.9%) [16, 33, 34]

  • 10 days (eradication rates of up to 83.1%) [5, 35, 6]
  • 10-14 days is recommended by the 2017 American College of Gastroenterology Guidelines [2]

Sequential therapy, an alternative first-line regimen, is as follows (eradication rates of up to 86.5%): [36, 16, 13, 2]

  1. PPI (esomeprazole 20 mg or 40 mg BID) plus amoxicillin (1 g BID) for 5-7 days, then

  2. PPI (esomeprazole 20 mg or 40 mg BID) plus levofloxacin (250 mg or 500 mg BID) plus a nitroimidazole antibiotic (eg, tinidazole 500 mg BID) for 5-7 days

A randomized trial investigated the role of bismuth in levofloxacin-containing 14-day sequential therapy, and concluded that adding bismuth did not significantly improve eradication rates (85.2% vs. 82.6%).

Concomitant therapy, another alternative first-line regimen, is as follows (eradication rates of up to 96.5%) [37] :

  • PPI (esomeprazole 40 mg BID) plus amoxicillin (1 g BID) plus levofloxacin (500 mg QD) plus another antibiotic (eg, tinidazole 500 mg BID) for 5 days

Concomitant bismuth AND levofloxacin-containing therapy

A group of Chinese researchers reported that the following regimen also provided satisfactory eradication rates in a population with high antibiotic resistance:

  • Esomeprazole 20 mg BID plus
  • Levofloxacin 500 mg BID plus
  • Bismuth 220 mg BID plus
  • Amoxicillin 1000 mg BID OR cefuroxime 500 mg BID

Duration: 14 days.  Eradication rates were not scientifically different between the amoxicillin and cefuroxime groups (83.5% vs. 81%). [38]

An open-label, randomized trial conducted in China reported acceptable eradication rates even for the following 1-week bismuth-containing regimen:

  • Esomeprazole 20 mg BID plus
  • Colloidal bismuth pectin 200 mg BID plus
  • Amoxicillin 1000 mg BID plus
  • Levofloxacin 500 mg OD OR clarithromycin 500 mg BID

The above levofloxacin-based concomitant quadruple regimen demonstrated a higher eradication rate (86.66% vs 76.22%). [39]

Second-line therapy

Second-line therapy [3, 40] should avoid repeating first-line regimens that were already used, and should incorporate at least one different antibiotic. Bismuth-based therapy or levofloxacin-containing triple therapy [40] can be used (same regimens as above, if not used previously).

Rescue or third-line therapy

Send ulcer biopsy specimen for antimicrobial culture and susceptibility before treatment. [3, 40, 4]   It is essential to avoid antimicrobials that have previously been used.  The preferred treatment for patients who have received a clarithromycin-containing first-line regimen are bismuth quadruple therapy or levofloxacin-salvage combination therapy.  In general, clarithromycin triple therapy is not recommended for salvage treatment.  [2]

Bismuth-based quadruple therapy (with amoxicillin, tetracycline, furazolidone, or metronidazole) is used for 14 days and comprises the following (eradication rates for all combinations below were above 90%) [41] :

  1. PPI (lansoprazole 30 mg BID) plus

  2. Bismuth potassium citrate 220 mg BID plus

  3. Tetracycline 500 mg QID or amoxicillin 1 g TID plus

  4. Furazolidone 100 mg TID or tetracycline 500 mg QID (if not already selected) or metronidazole 400 mg QID

For patients who already received bismuth quadruple therapy as first-line treatment, clarithromycin or levofloxacin-containing salvage regimens are preferred. [2]

Levofloxacin-based sequential therapy is superior to clarithromycin- and tetracycline-based therapies and consists of the following (eradication rates of up to 92.2%, as long as the H pylori was susceptible to levofloxacin): [17]

  1. PPI (esomeprazole 40 mg BID) + amoxicillin (1 g BID) for 7 days, then

  2. PPI (esomeprazole 40 mg BID) + metronidazole (500 mg BID) + levofloxacin (250 mg or 500 mg BID, with the former surprisingly achieving higher cure rates [13] ) for another 7 days

Other salvage regimens that can be recommended are the following [2] :

  1. Triple therapy (which includes levofloxacin) is also a recommended salvage regimen (see above)
  2. Concomitant therapy as described above
  3. 10-day rifabutin triple salvage regimen (PPI plus amoxicillin plus rifabutin) 
  4. High-dose dual therapy (PPI plus amoxicillin for 14 days) 

 

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Questions & Answers

Overview

Which empirical therapy regimens are used for eradication of Helicobacter pylori infection?

What is concomitant nonbismuth quadruple therapy for the eradication of Helicobacter pylori infection?

What is included in triple therapy for eradication of Helicobacter pylori infection?

How is nonbismuth quadruple therapy administered for eradication of Helicobacter pylori infection?

What is sequential nonbismuth quadruple therapy for the eradication of Helicobacter pylori infection?

What are eradication rates of sequential nonbismuth quadruple therapy for Helicobacter pylori infection?

What is hybrid nonbismuth quadruple therapy for the eradication of Helicobacter pylori infection?

What is reverse hybrid nonbismuth quadruple therapy for the eradication of Helicobacter pylori infection?

What is novel concomitant nonbismuth quadruple therapy for the eradication of Helicobacter pylori infection?

What is bismuth-based therapy for the eradication of Helicobacter pylori infection?

Which bismuth-based therapy for the eradication of Helicobacter pylori infection may be effective for antibiotic-resistant pathogens?

What is levofloxacin-containing therapy for the eradication of Helicobacter pylori infection?

What is sequential levofloxacin-containing therapy for the eradication of Helicobacter pylori infection?

What is concomitant levofloxacin-containing therapy for the eradication of Helicobacter pylori infection?

What are the second-line therapies for the eradication of Helicobacter pylori infection?

What are third-line therapies for the eradication of Helicobacter pylori infection?

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