The lecture was presented during the 13th annual conference of KLRC held in Alexandria 15 -17 August 2017 The lecture was directed to describe the current situation of H.Pylori infection in middle east ,particularly in Egypt , and to put some spotlights on the current regimens of treatment , and the situation of antibiotic resistance in Egypt and its impact on treatment choice

1. Refractory H.Pylori infection
Navigation through different
guidelines
By
Mohamed Hassany,MD.
Hepatology & Gastroenterology Consultant
National Hepatology & Tropical Medicine Research Institute
(NHTMRI)
KLC Conference , Hilton Green Plaza ,Alexandria , 17th August 2017.

2. Disclosure
• Nothing to disclose

3. Agenda
• Global and regional epidemiology
• Highlights on transmission and risk
• Rationale for testing and diagnosis
• Selection and re-selection of treatment

4. Agenda
• Global and regional epidemiology
• Highlights on transmission and risk
• Rationale for testing and diagnosis
• Selection and re-selection of treatment

6. H.Pylori prevalence in middle east
90
94
80 80
50 50
40
64
Egypt Libya KSA Turkey
Adults Children
World Gastroenterology Organization Global Guidelines ,2010

7. Prevalence of H pylori infection by age
in developing and developed countries

8. Agenda
• Global and regional epidemiology
• Highlights on transmission and risk
• Rationale for testing and diagnosis
• Selection and re-selection of treatment

10. Transmission of H.Pylori within families
H.Pylori positive
parent
Spouse : 68% HP +ve
Children : 40% HP +ve

11. Transmission of H.Pylori within families
H.Pylori negative
parent
Spouse : 9% HP +ve
Children : 3% HP +ve

12. Transmission of H.Pylori within families
H.Pylori +ve father
H.Pylori +ve mother
1x 2x

13. H pylori variable risk

15. Agenda
• Global and regional epidemiology
• Highlights on transmission and risk
• Rationale for testing and diagnosis
• Selection and re-selection of treatment

16. Indications for testing and treatment
• Past or present duodenal and/or gastric ulcer,
with or without complications
• Following resection of gastric cancer
• Gastric mucosa-associated lymphoid tissue
(MALT) lymphoma
• Atrophic gastritis
• Dyspepsia with or without alarming symptoms
• Patients with first-degree relatives with gastric
cancer
• Patient’s wishes
World Gastroenterology Organization Global Guidelines ,2010
ACG Clinical Guideline: Treatment of Helicobacter pylori Infection ,2017.

17. Positive predictive value for H.Pylori
detection in different diagnostic methods
99
88 84
64
0
20
40
60
80
100
120
Rapid urease test C13/C14 urea
breat test
Stool antigen ELISA serology
PPV
PPV
World Gastroenterology Organization Global Guidelines ,2010

18. Tips & Pitfalls in diagnosis
• The patient should be asked about previous
antibiotic exposure or H.Pylori treatment.
• Elisa serology is less accurate and does not
identify active infection , Not recommended
after therapy.

19. Tips & Pitfalls in diagnosis
• Avoid to perform stool antigen , urea breath
or urease test before 2 weeks of
discontinuation of (H2 receptor blockers ,PPI )
therapy or 4 weeks of antibiotic therapy.
• Preferred tests to confirm the eradication are
stool antigen or urea breath

20. Agenda
• Global and regional epidemiology
• Highlights on transmission and risk
• Rationale for testing and diagnosis
• Selection and re-selection of treatment

21. Factors involved in choosing treatment
regimens
1. Prevalence of H Pylori infection
2. Prevalence of gastric cancer
3. Availability of diagnostic facilities
4. Drug costs and availability and resistance profile
5. Drug allergies and tolerance
6. Previous treatments, outcome

22. First Line Therapy
Duration
/Days
FrequencyDrugsRegimen
14BIDPPI (dose/type)
Clarithromycin (500 mg)
Amoxicillin(1 gm) /Metronidazole(500 mg)
Standard Triple
10-14BIDPPI (dose/type)
Amoxicillin(1 gm)
Clarithromycin (500 mg)
Metronidazole(500 mg)
Concomitant
(NBQ)
5-7
5-7
BID
BID
PPI (dose/type)+Amoxicillin(1 gm) then
PPI (dose/type)+Clarithromycin (500 mg)
+Metronidazole(500 mg)
Sequential
(NBQ)
7
7
BID
BID
PPI (dose/type)+Amoxicillin(1 gm) then
PPI (dose/type)+Amoxicillin(1 gm)
+Clarithromycin (500 mg)
+Metronidazole(500 mg)
Hybrid
(NBQ)

23. First Line Therapy
Duration
/Days
FrequencyDrugsRegimen
7
7
BID
BID
PPI (dose/type)+Amoxicillin(1 gm)
+Clarithromycin (500 mg)
+Metronidazole(500 mg) then
PPI (dose/type)+Amoxicillin(1 gm)
Reverse Hybrid
(NBQ)
10TID
BID
BID
PPI +Amoxicillin(1 gm)+
Rifabutin 150 mg
Ciprofloxacin 500 mg
Novel
concomitant
therapy
(NBQ)
10-14BID
QID
QID
QID
PPI (dose/type)+
Bismuth subcitrate (120–300 mg) or
subsalicylate (300 mg) +
Metronidazole 250 mg
Tetracycline 500 mg
Bismuth Based

24. First Line Therapy
Levofloxacin Based
Duration
/Days
FrequencyDrugsRegimen
10-14BID
QD
BID
PPI (dose/type)
Levofloxacin (500 mg)
Amoxicillin(1 gm)
Levofloxacin
Triple
5-7
5-7
BID
BID
QD
BID
PPI (dose/type)+Amoxicillin(1 gm) then
PPI (dose/type)+Amoxicillin(1 gm)
+Levofloxacin (500 mg)
+Metronidazole(500 mg)
Levofloxacin
Sequential
7-10QD
QD
BID
QD
Levofloxacin (250 mg)
Omeprazole (40 mg)
Nitazoxanide (500 mg)
Doxycycline (100 mg)
LOAD

25. Tips & Pitfalls in therapy
• Check always for adherence and compliance
• Under dosage :Kindly avoid the formulas with
non-optimum dose
• Respect the relation to meals
• Not all PPIs have the same dose :
– Omeprazole 20 mg BID
– Lansoprazole 30 mg BID
– Rabeprazole 20 mg BID
– Esomeprazole 40 mg QD
– Pantoprazole 40 mg QD

26. Should we test for eradication ?
Whenever H. pylori infection is identified and
treated, testing to prove eradication should be
performed using a urea breath test, fecal
antigen test or biopsy-based testing at least 4
weeks after the completion of antibiotic therapy
and after PPI therapy has been withheld for 1–2
weeks (strong recommendation; low quality of
evidence)
ACG Clinical Guideline: Treatment of Helicobacter pylori Infection ,2017.

27. Which regimen should I select ?

29. H.Pylori antimicrobial resistance
World Gastroenterology Organization Global Guidelines ,2010

30. Resistance profile for different H.Pylori
antimicrobials
0
20
40
60
80
100
120
Zaki M et al
Zaki M et al
Hasanein W et al
Ramzy I et al
Khalil K et al
Fathi M et al
Sherif M et al (children)
Zaki M et al ,Journal of Microbiology and Antimicrobial Agents. 2016; 2 (1): 26-31.
Zaki M et al , Int.J.Curr.Microbiol.App.Sci (2016) 5(1): 165-173
Hasanein Wet al ,abstract. 7th Conferance on new frontiers in microbiology and infection,2011.
Ramzy I et al, Rev Inst Med Trop Sao Paulo. 2016;58:88.
Khalil K et al , Egyptian Journal of Medical Microbiology, April 2014
Fathi M et al , The Egyptian Journal of Medical Human Genetics (2013) 14, 235–246
Sherif M et al , Journal of Clinical Microbiology. 2004;42(10):4832-4834.

31. Heep M, et al. Eur J Clin Microbiol Infect Dis 2000;19:538-41.

32. Second Line Therapy
• 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 can be used (same
regimens as mentioned, if not used
previously).
Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report.2012.
ACG Clinical Guideline: Treatment of Helicobacter pylori Infection ,2017.

33. Second Line Therapy
Duration
/Days
FrequencyDrugsRegimen
14BID
QID
QID
QID
PPI (dose/type)+
Bismuth subcitrate (120–300 mg) or
subsalicylate (300 mg) +
Metronidazole 250 mg
Tetracycline 500 mg
Bismuth Based
14BID
QD
BID
PPI (dose/type)
Levofloxacin (500 mg)
Amoxicillin(1 gm)
Levofloxacin
Triple

34. Rescue or third-line therapy
• biopsy specimen should be sent for
antimicrobial culture and susceptibility before
treatment.
Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report.2012
Duration
/Days
FrequencyDrugsRegimen
14BID
BID
QID
QID
PPI (Lansoprazole 30 mg)+
Bismuth subcitrate 220 mg
Metronidazole 400 mg
Tetracycline 500 mg
Bismuth Based
7
7
BID
BID
PPI (Esomeprazole 40 mg)+Amoxicillin(1 gm)
then
PPI (Esomeprazole 40 mg)+Metronidazole
500 mg+Levofloxacin (500 mg)
Levofloxacin
Sequential

35. Role of probiotics
• There is growing interest of probiotics as adjuvant
therapy in the treatment of H. pylori infection.
• Emerging evidence suggests an inhibitory effect
of Lactobacillus and Bifidobacterium species on
H. pylori.
• These probiotic strains may also help to reduce
the side effects of eradication therapies and
improve compliance with therapy
Zhang MM , et al.. World Journal of Gastroenterology 2015 ; 21 : 4345 – 57

36. Creation of our own guidelines
and consensus report

37. Creation of our own guidelines
and consensus report

41. THANK YOU