Management of Helicobacter pylori infection in Greece: Current guidelines 4th Athens International Symposium on Digestive Diseases, Athens Greece 6-7 July 2018 Chris Zavos, MD, PhD, FEBGH http://peptiko.gr

1. Management of Helicobacter pylori
infection in Greece: Current guidelines
Chris Zavos, MD, PhD, FEBGH
Board-certified Gastroenterologist
Thessaloniki, Greece
4th Athens International Symposium on Digestive
Diseases – 7 July 2018

2. Conflicts of Interest: None

3. 3

4. H. pylori eradication regimens in 2018

5. Antibiotic Resistance

7. H. pylori antibiotic primary resistance in Greece
Significant increase in secondary resistance to LEVO: 23.5% !
Years H. pylori
strains (N)
AMO
(%)
MET
(%)
CLA
(%)
TET
(%)
LEVO
(%)
Author
1998 43 46 2.3 Kallergi
2001 66 1.5 47 10 Mentis
2008-09 117 37.6 23.1 7.7
Martinez-
Gonzalez
2011-12 106 37.7 23.6 11.3
Martinez-
Gonzalez
2012-14 230 34.8 26.5 9.1
Martinez-
Gonzalez

8. Concomitant resistance (Greek data)
• 1st
Line
• MET+LEVO: 2.4%
• CLA+LEVO: 1.2%
• MET+CLA+LEVO: 1.5%
• 2nd
Line
• MET+LEVO: 13.9%
• CLA+LEVO: 3.3%
• MET+CLA+LEVO: 5.3%

9. Relationship between CLA resistance and
treatment success
Rimbara E, et al. Nat Rev Gastroenterol Hepatol 2011;8:79-88

10. Grade %Eradication
(ITT)
Outcome
A ≥95% Excellent
B 90-94% Good
C 85-89% Acceptable
D 81-84% Poor
F (FAIL) ≤80% Not acceptable

11. Legendary triple therapy
Medications Duration Success rate
PPΙ x2 7-14 d <50%
AMO 1 g x2
CLA or MET 500 mg x2
Dore MP, et al. Dig Dis Sci 2000;45:68-76.
Chen Y-I, et al. Can J Gastroenterol Hepatol 2015;29:e7-e10.
Yuan Y, et al. Cochrane Database Syst Rev 2013;12:CD008337.

12. Legendary triple therapy in Southern Europe
Graham DY et al. Gut 2010;59:1143-53

13. Therapy choices in Greece inTherapy choices in Greece in
20120188??

14. Available treatment choices in Greece
1st
Line
Legendary triple Not acceptable eradication rate
Quadruple concomitant 10-14 d w/o bismuth
Quadruple sequential 5+5 d
Quadruple hybrid 14 d
2nd
Line (at least 1 failure)
LEVO-containing regimens
3rd
Line (at least 2 failures)
Culture Recommended
High-dose dual PPI + AMO Empiric therapy
Triple regimen containing rifabutin “Last resort”
Not available in Greece
TET / Bismuth

15. Concomitant quadruple
Medications Duration Success rate
PPI x2 10-14 d. 89.1% (ITT)
93.4% (PP)
AMO 1 g x2
CLA 500 mg x2
MET 500 mg x2
Georgopoulos SD, et al. Helicobacter 2014;19 (Suppl. 1)

16. Sequential quadruple
Medications Duration Success rate (ITT)
PPI x2 + AMO 1 g x2 5 d. 78.7-84%
PPI x2 + CLA 500 mg x2 + MET 500 mg x2 5 d.
Georgopoulos SD, et al. Helicobacter 2014;19 (Suppl. 1)
Kalapothakos et al. UEG J 2014; Suppl 1
Georgopoulos SD, et al. Eur J Intern Med 2016; in press

17. Quadruple hybrid
Medications Duration Success rate (ITT)
PPI x2 + AMO 1 g x2 7 d. 91%
PPI x2 + ΑΜΟ 1 g x2 + CLA 500 mg x2 +
MET 500 mg x2
7 d.
• Limited data
• Inferior to concomitant quadruple
• High success rate in dual CLA+MET
Kalapothakos et al. UEG J 2014; Suppl 1:
He L, et al. Intern Med 2015;54:703-10

18. 2nd
Line treatment with LEVO
• Similarly effective after failure of both sequential (81%) and concomitant
(78%) 1st
line treatment
• Similar eradication rates with 500 mg (either once a day or 250 mg
twice a day) and 1000 mg (500 mg twice a day) of LEVO
• PPI+AMO+MOXI (instead of LEVO)  success rate: 71%
• PPI+AMO+LEVO+BISMUTH  success rate: >90%
Medications Duration Success rate (ITT)
PPI x2 + AMO 1 g x2 + LEVO 500 mg x1 10-14 d 78-84%
Malfertheiner P, et al. Gut 2016 Oct 5

19. 3rd
Line treatment guided by culture and
susceptibility testing or molecular
determination of genotype resistance
• Adding Bismuth is recommended (though not available in Greece)
Medications Duration
PPI x2 10-14 d
1st
antibiotic guided by culture
2nd
antibiotic guided by culture

20. Empiric therapy in Greece
Medications Duration Success rate
Esomeprazole x3 + AMO 1 g x3 10 d. 87.5%
Zullo A, et al. Ann Gastroenterol 2015;28:448-51
Medications Duration Success rate
PPI x4 + AMO 500 mg x4 14 d Undetermined
Rimbara E, et al. Nat Rev Gastroenterol Hepatol 2011;8:79-88

21. Rifabutin: “Last resort”
Medications Duration Success rate (ITT)
PPI x2 + AMO 1 g x2 + RFB 150 mg x2 10 d 78.5%
Toracchio S, et al. Dig Liver Dis 2005;37:33-8
Medications Duration Success rate (ITT)
PPI x4 + AMO 500 mg x4 + RFB 300 mg x1 10 d.
14 d.
83.3%
94.1%
Mori H, et al. UEG J 2016;4:380-7

22. • Meta-analyses have consistently shown that the efficacy of concomitant
therapy is duration-dependent
Duration of treatment

24. Homan M, World J Gastroenterol 2015;21:10644-53Lau CS, et al. Infect Drug Resist
2016;9:275-289.
Triple Hp eradication
regimens

25. • Probiotics in quadruple therapies showed no additional benefit in H.
pylori eradication rates, and only a reduction in the rate of adverse
events was recorded (such as nausea, vomiting, epigastric pain,
and mainly diarrhea)
Quadruple therapies
Manfredi M, et al. Helicobacter 2012;17:254-63.
Shavakhi A, et al. Helicobacter 2013;18:280-4.

26. Therapeutic indications:
1. mild dyspeptic disorders
2. healing of minor wounds
Chios mastic
ema.europa.eu (2015)

27. • Might be considered as:
•Adjuvant therapy with antibiotics for optimization of treatment
Or
•Single alternative treatment in high doses in patients with
serious adverse events or who are unwilling to receive
eradication regimen with antibiotics
Chios mastic against H. pylori

28. Take-home messages
• Hp resistance is increasing worldwide (CLA, MET, LEVO)
• Legendary triple ineffective in Greece  should be abandoned
• Greece: Bismuth and Tetracycline not available
• 1st
Line: (Concomitant 4ple = hybrid) > Sequential
• 2nd
Line: Concomitant 3ple with LEVO
• 3rd
Line: Culture-guided or high-dose dual PPI+AMO or 3ple with RFB
(PPI, AMO, RFB) as a “last resort”