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

2. 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

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

4. 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

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. STEPS IN THERAPY OF Hp
Diagnosis
Therapy
Confirm cure

9. 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

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

11. 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.

12. Current Therapies Clarithromycin based therapy Bismuth based therapy
PPI, amox, metronidazole
Fluoroqunilone based
Rifabutin based
Triple
Quadruple
7, 10 or 14 days duration

14. 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

15. 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

16. Other Common Regimes Triple metronidazole therapy
PPI+Amoxicillin+Metronidazole
Triple fluroroquinolone therapy
PPI+Amoxicillin+Levofloxacin
Bismuth Quadruple therapy
PPI+Bismuth+Metro+Tetracycline

17. Empiric Therapies Clarithromycin based: Amoxicillin (1 g), BID
Clarithromycin (500 mg), BID
Tinidazole (500 mg) or Metronidazole (500 mg) BID
PPI (40 mg omeprazole equivalent per dose) BID
14 days
Bismuth quadruple therapy:
Bismuth subsalicylate 2 tablets QID
Tetracycline hydrochloride (500 mg) QID
Metronidazole/tinidazole (500 mg) TID
PPI twice daily for 14 days (40 mg omeprazole equivalent per dose). Not Doxycycline

18. Salvage Therapies: After at least 2 failures with different antimicrobials
Rifabutin triple therapy
(best if susceptibility-based)
Rifabutin (150 mg daily),
Amoxicillin (1.5 g q.8.h.
Pantoprazole 80 mg (or an equivalent PPI) q.8.h. for 14 days,
consider adding Bismuth 2 tabs bid
High dose PPI-amoxicillin dual therapy
PPI (e.g. esomeprazole 40 mg) QID
Amoxicillin (750 mg) QID
14 days

19. 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 %

20. 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%

21. 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%

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. 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

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
<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

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%
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

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%
<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

27. 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
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%

28. Bismuth Quadruple “Modified” Amoxicillin 1gm BID
Bismuth subsalicylate 2 tablets QID
Tetracycline hydrochloride (500 mg) QID
Metronidazole (500 mg) TID
PPI BID
14 days.
Tetracycline is difficult to obtain
Doxycycline is not a useful substitute!
Helidac (not currently available)
Amoxicillin 1gm BID

29. Bismuth subcitrate 140mg
Metronidazole 125mg
Tetracycline 125mg
3 tabs QID
+ a PPI BID e.g.
omeprazole 40mg BID

30. 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.

31. 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

32. Treatment Failures Ensure compliance
Avoid antibiotics used before (history)
Fluoroquinolones
Rifabutin
PPI – Amoxicillin high dose
Susceptibility based: Culture for antimicrobial sensitivities

33. In particular, don’t use these again
Clarithromycin
Fluoroquinolones (eg, levofloxacin)
Rifabutin
PPI + clarithromycin + amoxicillin becomes PPI + amoxicillin

34. 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

35. 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.

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

37. 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

38. 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

39. Keys to Success Use what is effective locally
Use it exactly (dose, duration, etc)
In treatment failures, base therapy on measured susceptibility testing (Tailored therapy)
Confirm cure in all (UBT or Stool)

40. References