1. What’s New in Helicobacter Pylori Therapy
Waqar Qureshi, MD,
Professor of Medicine,
Clinical Director of Gastroenterology,
Baylor College of Medicine,
Houston, Texas

2. Helicobacter pylori
H. pylori is a serious chronic transmissible infectious disease that causes damage to gastric structure and function and is a major cause of morbidity and mortality worldwide.
The prevalence of H. pylori is inversely related to the general health and well being of a society.
It should be eradicated

3. Kyoto Global Consensus Report on H. pylori gastritis
“H pylori-infected individuals should be offered eradication therapy, unless there are competing considerations”.
Gut: (in press)

4. OUTCOMES OF H. PYLORI INFECTION
Gastric Cancer
Environmental
Factors
Atrophic
Gastritis
Gastric Ulcer
Acute
Gastritis
Acute-on-Chronic Gastritis
Lymphoma
Antral
Predominant
Gastritis
Duodenal Ulcer
Childhood Mid-life Old Age

5. WHOM TO TEST Dyspepsia (symptomatic Hp?) Ulcer Disease Gastric cancer
Present or past history
1st degree relatives
Gastric cancer
Family history gastric cancer
After endoscopic resection of gastric cancer

6. Evaluate Hp eradication Family members of infected
WHOM TO TEST
Plan to start therapy
Chronic NSAID therapy
Chronic PPI therapy (eg, GERD)
Evaluate Hp eradication
Family members of infected
Patient desires to be tested

7. Whom to Treat for Hp
All with active Hp infection unless there is a compelling reason not to

8. H. pylori Causes Peptic ulcer disease (1 in 6)
Gastric cancer (1 to 19%)
Progressive gastric damage
Iron deficiency
B12 deficiency
Recuced absorption of drugs requiring an acid stomach such as L-dopa & throxine

9. Diagnosis Therapy Confirm cure STEPS IN THERAPY OF Hp
All active Hp infection should be treated unless there is a compelling reason not to

10. Hp is an Infectious Disease
Hp therapies either succeed or fail
There is no partial success
Primary causes of failure
Resistance to one or more antibiotics
Adherence with drug regimen

11. Scoring “Effective” Treatment Regimens
Outcome
Success*
Excellent: >95%
Good: >90%
Borderline: %
Unacceptable <84%
* Per Protocol: reliably with susceptible strains.

12. The Present No new therapies approved for more than a decade
Old therapies have become relatively ineffective (eg, 70% cure rates)
Overall prevalence decreasing but still high in subpopulations (31% in VA population), 70%+ in Hispanic and Asian immigrants.

13. Current First Line Therapies
Clarithromycin based therapy
Bismuth based therapy
Triple
Quadruple
7, 10 or 14 days duration

15. PPI – Amox –Clari Therapy
100
Hong Kong n = 592 80
Taiwan n = 1200
U.S. n = 1255
Europe n = 3752
Korea n = 598
China n = 148 60
ITT Cure Rates (%; 95% CI) 40
Japan n = 1323 20
Results of Recent Trials

16. Clarithromycin-Containing Regimes
Triple therapy (3 drugs)
PPI+Amoxicillin+Clarithromycin
Concomitant therapy (4 drugs)
PPI+Amox+Clari+Metro
Sequential therapy (4 drugs)
PPI+Amox then PPI+Clari+Metro

17. Other Common Regimes Triple metronidazole therapy
PPI+Amoxicillin+Metronidazole
Triple fluroroquinolone therapy
PPI+Amoxicillin+Levofloxacin
Bismuth Quadruple therapy
PPI+Bismuth+metro+tetracycline

18. Treatment Comparison - Susceptible Strains (PP) -
Therapy Days Success
Clarithromycin triple therapy %
Clarithromycin triple therapy %
Sequential therapy %
Sequential therapy %
Fluoroquinolone triple <80%
Fluoroquinolone triple <90%
Fluoroquinolone triple %

19. Treatment Comparison – 2 - Susceptible Strains (PP) -
Therapy Days Success
PPI metronidazole triple %
PPI metronidazole triple %
PPI bismuth tetra metro %
PPI bismuth tetra metro %
PPI bismuth tetra metro >95%
PPI + amoxicillin %
PPI + amoxicillin %
PPI + amoxicillin %

20. Treatment Comparison - With Resistant Strains (PP) -
Therapy Days Success
Clarithromycin triple therapy <20%
Clarithromycin triple therapy <50%
Sequential therapy (dual) <20%
Sequential therapy (dual) <20%
Fluoroquinolone triple <20%
Fluoroquinolone triple <20%
Fluoroquinolone triple <50%

21. Effect of Clari Resistance 7 day Triple
PPI + Amox + Clari (94%) +
PPI + Amox (10%)

22. 7 Day Clari-Triple Rx PP 100 80 Treatment Success (%) 60 40 20
94% 80
Susceptible 60
Treatment Success (%) 40 20
10%
Clari Res
Triple Rx
Dual (PPI +A)

23. Useful History Details of the prior regimen How many times attempted?
Type and dose and antibiotics?
Type and dose of PPI?
Any adjuvant (e.g., probiotics)?
How many times attempted?
Any drug allergies or inabilities to take one or more drugs?

24. Predict Success for an Individual Patient
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
94%
7 day Clari Triple
97%
14 day Clari Triple
95%
10 day Sequential
98+%
14 day Sequential
97+%
14 day Concomitant

25. Predict Success for an Individual Patient
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
<20%
94%
7 day Clari Triple
97%
<50%
14 day Clari Triple
95%
80%
10 day Sequential
98+%
88%
14 day Sequential
97+%
97%
14 day Concomitant/Hybrid

26. Predict Success for an Individual Patient
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
<20%
94%
94%
7 day Clari Triple
<50%
97%
97%
14 day Clari Triple
95%
80%
75%
10 day Sequential
98+%
88%
75%
14 day Sequential
97+%
97%
97%
14 day Concomitant

27. Predict Success for an Individual Patient
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
<20%
94%
94%
<20%
7 day Clari Triple
97%
<50%
97%
<50%
14 day Clari Triple
95%
80%
75%
<20%
10 day Sequential
98+%
88%
75%
<20%
14 day Sequential
97+%
97%
97%
<50%
14 day Concomitant

28. Regimens Concomitant: b.i.d. for 14 days
PPI (40 mg omeprazole or equivalent)
Amoxicillin 1000 mg
Clarithromcyin 500 mg
Metronidazole 500 mg

29. Previously treated for H. pylori
Bismuth Quadruple Rx
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscep
Clari
Resistan
Metro
Resistan
Dual
Resistant
Regimen
7 day bismuth quadruple
91%
n/a
75%
n/a
10 day bismuth quadruple
93%
n/a
85%
n/a
n/a
95%
n/a
14 day bismuth quadruple
99%

30. Previously treated for H. pylori
Bismuth Quadruple Rx
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
7 day bismuth quadruple
91%
10 day bismuth quadruple
93%
14 day bismuth quadruple
99%

31. Previously treated for H. pylori
Bismuth Quadruple Rx
Prior antibiotic use
Previously treated for H. pylori
Predict Resistance
Treatment outcome (per protocol)
All Suscept
Clari
Resistant
Metro
Resistant
Dual
Resistant
Regimen
7 day bismuth quadruple
91%
n/a
75%
n/a
10 day bismuth quadruple
93%
n/a
85%
n/a
n/a
95%
n/a
14 day bismuth quadruple
99%

32. Bismuth Quadruple Tetracycline is difficult to obtain
Doxycycline is not a useful substitute!
Helidac (other packaged product, not currently available
Give for 14 days

33. + a PPI

34. Recommended Empiric Regimens (14 days)
Concomitant therapy
Bismuth quadruple therapy
Currently only Pylera available (give for 14 days) + PPI
Do not use doxycycline
PPI: always use 40 mg omeprazole or equivalent b.i.d.

35. Keys to Success Use what is effective locally
Use it exactly (dose, duration, etc)
Base therapy on measured susceptibility testing (Tailored therapy)
Confirm cure in all cases

36. Initial Approach 2015 H. pylori infected History of antibiotic use?
Previously treated for H. pylori?
Treatment naive
Treatment naive
Prior treatment Failure
Prior treatment Failure
14 day concomitant Rx
14 day bismuth quadruple
Alternate best local Rx

37. Treatment Failures Antimicrobials not used before Fluoroquinolones
Rifabutin
PPI – Amoxicillin high dose

38. 14 day Fluoroquinolone Amoxicillin 1 gram b.i.d.
Levo 500 or Moxi 400 once a day
PPI b.i.d.
14 days (7 and 10 day = poor results)
Can not be used if a fluoroquinolone has been used in the past
Best if based on culture and susceptibility testing
Miehlke: Helicobacter 2011:16:420

39. Rifabutin Triple Rx Rifabutin 150 mg once daily (b.i.d.?)
Amoxicillin 1.5 g t.i.d.
Pantoprazole 80 mg t.i.d. (or equivalent)
(Consider adding bismuth 2 tabs b.i.d.)
All for 14 days
* We need more studies and confirmation
Borody: Aliment Pharmacol Ther 2006;23:481.

40. High Dose PPI-Amox
PPI (eg, 40 mg esomeprazole) plus Amoxicillin 750 mg every 6 hours for 14 days.

41. Choice for a Population
Depends on resistance patterns
14 day triple (only when all susceptible)
14 day concomitant
14 day bismuth quadruple (dual resistance)
Should yield >90% eradication

42. Clari-Containing Regimens - Conclusions -
High prevalence of clari AND met resistance (high dual resistance)
No clari-containing regimen is useful when the is a high prevalence of dual resistance

43. References