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Treatment of H. pylori infectionMaastricht IV/ Florence consensus reportSamir Haffar M.D.Assistant Professor of Gastroente...
European Helicobacter Study GroupFounded in1987• 1996 Maastricht I consensus reportEur J Gastroenterol Hepatol 1997 ; 9 : ...
Responses to therapy for typical GI diseaseIBS, IBDGraham DY et al. Helicobacter 2011 ; 16 : 343 – 345.< 100% success expe...
Clinical trial of H. pylori therapyGraham DY & Dore MP. Helicobacter 2011 ; 16 : 343 – 345.100% or near 100% success expec...
Grading system of H. pylori therapyGraham DY et al. Helicobacter 2007 ; 12 : 275 – 278.Grade Cure rate (ITT) ScoreA ≥ 95% ...
Bacterial factorsPrimary resistance to antibioticsBacterial load in stomachBacterial coccoid formscagA status (negative)va...
H. pylori resistance to antibiotics• Clarithromycin Not overcome by increasing dose & duration„all or none‟ Should not be ...
H. pylori & antibiotic resistance in middle eastCountry No.testedAMO%MTZ%CLA%Quinolones%TET%Furazolidone%Iran2007101 21 73...
H. Pylori & antibiotic resistance• Cross-resistance in each family of antibioticsResistance to clarithromycin → resistance...
HP & phenotypical antibiotic resistanceScott D et al. Gut 1998 ; 43(Suppl 1): S56 – S60.Graham et al. Gut 2010 ; 59 : 1143...
Smoking & eradication of H. pylori22 studies – 5538 patients – Random effectSuzuki T et al. Am J Med 2006 ; 119 : 217 – 22...
Difficulties associated with cure of H. pylori• Development of H pylori resistance to many agents:Metronidazole, clarithro...
Annual recurrence of H. pylori after successfuleradication in developing countriesEach bar represents a different studyRec...
Optimal antimicrobial therapies• Dosage• Dosing intervals• Formulation• Route of administration• Duration of therapyEstabl...
Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential...
Standard triple therapy (PAC)Most widely used & approved therapy• PPI Standard dose, bid• Amoxicillin 1 g, bid• Clarithrom...
Treatment success for triple therapyintention-to-treat analysis (ITT)Line at 80% treatment successDemarcation between acce...
Improving standard triple therapy (PAC)• Increase dose of PPIEsomeprazole 40 mg bid increases eradication by 8 – 12%• Incr...
• PPI Standard dose, bid• Metronidazole 500 mg, bid• Clarithromycin 500 mg, bidFor 7 – 10 – 14 daysPAC & PMC regimens are ...
Sequential therapy‘‘five plus five’’ day therapy• 1st five days PPI (standard dose, bid)Amoxicillin (1 g, bid)• 2nd five d...
Rationale of sequential therapySequential antibiotic administration not recommended“fear to promote drug resistance”.• Seq...
Sequential versus standard triple therapy15 RCTs – ITT – Random effect modelGisbert JP et al. J Clin Gastroenterol 2010 ; ...
Limitations of sequential therapy• Low validation outside Italy• Small sample size: < 50 in some protocols• Low quality of...
Concomitant therapy“Non-bismuth quadruple therapy”• PPI Standard dose, bid• Amoxicillin 1 g, bid• Clarithromycin 500 mg, b...
Concomitant therapy for treatment of H pyloriMeta-analysis – 15 RCTs (1723 pts – Random effectGisbert J P et al. Aliment P...
Sequential-concomitant therapy‘‘Hybrid therapy’’• 1st seven days PPI (standard dose, bid)Amoxicillin (1 g, bid)• 2nd seven...
Bismuth quadruple therapy (BMT)Underutilized in clinical practice• PPI Standard dose, bid• Bismuth subcitrate 420 mg, qid•...
Treatment regimen according to areas of Clari-RMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.1st linePPI-Amoxicillin-Cla...
Mégraud F. Presse Med. 2010 ; 39 : 815 – 822.Malfertheiner P et al. Gut 2012; 61: 646 – 664.Antibiotics Stopped for at lea...
Confirmation of eradication for H. pyloriNon-endoscopic methodsTests Sensitivity SpecificitySerologyELISA IgG70 – 90%70 – ...
Treatment of H pylori-positive peptic ulcer• Uncomplicated DUProlongs PPI not recommended after HP treatment (Grade A)• GU...
Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential...
Levofloxacin-based triple therapySecond line therapy• PPI Standard dose, bid• Amoxicillin 1 g, bid• Levofloxacin 500 mg, q...
Treatment regimen according to areas of Clari-RRegion with low Clari-R< 20%Region with high Clari-R> 20%1st linePPI-Amoxic...
Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential...
Culture-guided therapyThird line therapy• PPI Standard dose, bid• Bismuth 2 tablets, qid• 1st antibiotic Selected by antim...
Susceptibility testing• Culture & standard susceptibility testing (preferable)Practical for Clarithromycin & Levofloxacin ...
Fluorescence in situ hybridisation (FISH)Clarithromycin susceptibility of HP on gastric biopsyRimbara E & Graham DY. Nat R...
High-dose dual PPI therapyEmpirical third line therapy• PPI (high dose) Omeprazole 40 mg, qidorLansoprazole 30 mg, qid• Am...
Furazolidone-based quadruple therapyEmpirical third line therapy• PPI Standard dose, bid• Bismuth Standard dose, qid• Tetr...
Furazolidone• Produced commercially since 1955• Antibacterial & antiprotozoal in human & veterinary medicine• No longer ma...
Furazolidone-based quadruple therapySystematic reviewZullo A et al. Saudi J Gastroenterol 2012 ; 18 : 11 – 17.
Rifabutin-based triple therapyEmpirical third line therapy – Drug of last resort• PPI Standard dose, bid• Amoxicillin 1 g,...
RifabutinRifamycin-S derivative• Indications Mycobacteria including MAC*Third line treatment of H pylori• Eradication 3rd ...
Rifabutin-based triple therapyEmpirical third line therapyGisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.
2nd line*Bismuth quadruplePPI-Amoxicillin-LevofoxacinPPI-Amoxicillin-LevofoxacinTreatment regimen according to areas of Cl...
Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.* Regimen should not include antibiotics given previouslyTreatment in pati...
Cautions associated with anti-HP antimicrobials• Nitroimidazole Carcinogenicity (Group 2B – IARC)Antibuse-like reaction• F...
General recommendations for H. pylori treatment• 1st line therapy Avoid CLA if given for any indicationAvoid LEV if given ...
References
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Treatment of Helicobacter pylori infection - Maastricht IV/ Florence consensus report

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Treatment of Helicobacter pylori infection - Maastricht IV/ Florence consensus report

  1. 1. Treatment of H. pylori infectionMaastricht IV/ Florence consensus reportSamir Haffar M.D.Assistant Professor of Gastroenterology
  2. 2. European Helicobacter Study GroupFounded in1987• 1996 Maastricht I consensus reportEur J Gastroenterol Hepatol 1997 ; 9 : 1 – 2.• 2000 Maastricht II consensus reportAliment Pharmacol Ther 2002 ; 16 : 167 – 80.• 2005 Maastricht III consensus reportMalfertheiner P et al. Gut 2007 ; 56 : 772 – 81.• 2010 Maastricht IV/ Florence consensus report44 experts from 24 countriesMalfertheiner P et al. Gut 2012 ; 61 : 646 – 664.
  3. 3. Responses to therapy for typical GI diseaseIBS, IBDGraham DY et al. Helicobacter 2011 ; 16 : 343 – 345.< 100% success expectedPlacebo generally needed
  4. 4. Clinical trial of H. pylori therapyGraham DY & Dore MP. Helicobacter 2011 ; 16 : 343 – 345.100% or near 100% success expectedNo placebo responseFailure almost always explainable: Resistance – Flawed regimen
  5. 5. Grading system of H. pylori therapyGraham DY et al. Helicobacter 2007 ; 12 : 275 – 278.Grade Cure rate (ITT) ScoreA ≥ 95% ExcellentB 90 – 94 % GoodC 85 – 89 % AcceptableD 81 – 84 % PoorF ≤ 80% UnacceptableSimilar to grade performance of school childrenFailed
  6. 6. Bacterial factorsPrimary resistance to antibioticsBacterial load in stomachBacterial coccoid formscagA status (negative)vacA alleles status (s2m2 allele)dup A status*Factors affecting H. pylori eradication success* dup: duodenal ulcer promotingZullo A et al. J Clin Gastroenterol 2012 ; 46 : 259 – 261.Host factorsCompliance to therapyGastric acid hypersecretionGenetic polymorphism of CYP 450Gastroduodenal disease (NUD)Gastritis pattern (pangastritis)ObesitySmoking
  7. 7. H. pylori resistance to antibiotics• Clarithromycin Not overcome by increasing dose & duration„all or none‟ Should not be used if prevalence > 15 – 20%• Levofloxacine Not overcome by increasing dose & duration„all or none‟ Rapidly increasing worldwide• Metronidazole Overcome by increasing dose & duration„not all or none‟ Should not be used if prevalence > 40%• Amoxicillin Rare in most regions• Tetracycline Rare in most regions• Bismuth Does not occurGraham DY et al. Drugs 2008 ; 68 : 725 – 736.
  8. 8. H. pylori & antibiotic resistance in middle eastCountry No.testedAMO%MTZ%CLA%Quinolones%TET%Furazolidone%Iran2007101 21 73 9 5 5 9Egypt200448 2 100 4 2KSA2002223 1 80 4 0.5Kuwait200696 0 70 0 0WGO global guideline. J Clin Gastroenterol 2011 ; 45 : 383 – 388.
  9. 9. H. Pylori & antibiotic resistance• Cross-resistance in each family of antibioticsResistance to clarithromycin → resistance to all macrolidesResistance to levofloxacin → resistance to all fluoroquinolones• No cross-resistance between different families of antibiotics• Important to use compound indicated to get good resultsClarithromycin for macrolidesTetracycline HCl and not doxycyclineLevofloxacin but not ciprofloxacin for fluoroquinolonesMalfertheiner P et al. Management of HP infection: the Maastricht IV/Florence consensus report.Gut 2012 ; 61: 646 – 664.
  10. 10. HP & phenotypical antibiotic resistanceScott D et al. Gut 1998 ; 43(Suppl 1): S56 – S60.Graham et al. Gut 2010 ; 59 : 1143 – 1153.pH 4 – 8: H. pylori survivespH 4 – 6: Non-dividing H. pylori – Phenotypical resistancepH 6 – 8: Dividing H. pylori – Susceptible to AMO or CLA
  11. 11. Smoking & eradication of H. pylori22 studies – 5538 patients – Random effectSuzuki T et al. Am J Med 2006 ; 119 : 217 – 224.Differences of smokers & nonsmokers 8.4% (95% CI: 3.3-13.5%)
  12. 12. Difficulties associated with cure of H. pylori• Development of H pylori resistance to many agents:Metronidazole, clarithromycin & fluoroquinolones• Huge number of HP organisms present in the stomach,which produces an inoculum effect• H. pylori organisms can reside in variety of niches:Intracellularly or in highly acidic gastric mucus gel layer• High rate of reinfection in developing countriesRimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.H. pyori, like tuberculosis, requires treatment withmultiple drugs for long duration
  13. 13. Annual recurrence of H. pylori after successfuleradication in developing countriesEach bar represents a different studyRecurrence of original infection or reinfection with new strainRimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
  14. 14. Optimal antimicrobial therapies• Dosage• Dosing intervals• Formulation• Route of administration• Duration of therapyEstablish parameters that will provide the bestoutcome from a particular regimen:Rimbara E. et al. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
  15. 15. Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential-concomitant therapyBismuth quadruple therapy“legacy triple therapy”“five plus five day therapy”“non-bismuth quadruple therapy”“hybrid therapy”underutilized in practiceSecond line treatment (one treatment failure)Levofloxacin triple therapyThird line treatment (at least 2 treatment failures)Culture-guided therapyHigh-dose dual PPI therapyFurazolidone quadruple therapyRifabutin-based triple therapyRecommendedEmpiricalEmpiricalEmpirical – Last resort
  16. 16. Standard triple therapy (PAC)Most widely used & approved therapy• PPI Standard dose, bid• Amoxicillin 1 g, bid• Clarithromycin 500 mg, bidFor 7 – 10 – 14 daysStandard triple therapy without prior susceptibility testingshould be abandoned when Clari-R > 15 – 20%Malfertheiner P et al. Management of HP infection: the Maastricht IV/Florence consensus report.Gut 2012 ; 61: 646 – 664.
  17. 17. Treatment success for triple therapyintention-to-treat analysis (ITT)Line at 80% treatment successDemarcation between acceptable & unacceptably success rateEach bar represents a different studyGraham DY & Fischbach L. Gut 2010 ; 59 : 1143 – 1153.
  18. 18. Improving standard triple therapy (PAC)• Increase dose of PPIEsomeprazole 40 mg bid increases eradication by 8 – 12%• Increase length of treatment10-day treatment Increases eradication by 4%14-day treatment Increases eradication by 5 – 6%• Adjuvant treatment Lactoferrin – S. boulardiiPromising resultsMore studies neededMalfertheiner P et al. Management of HP infection: the Maastricht IV/Florence consensus report.Gut 2012 ; 61: 646 – 664.
  19. 19. • PPI Standard dose, bid• Metronidazole 500 mg, bid• Clarithromycin 500 mg, bidFor 7 – 10 – 14 daysPAC & PMC regimens are equivalentShould not be used if metronidazole resistance > 40%Standard triple therapy (PMC)Most widely used & approved therapyMalfertheiner P et al. Management of HP infection: the Maastricht IV/Florence consensus report.Gut 2012 ; 61: 646 – 664.
  20. 20. Sequential therapy‘‘five plus five’’ day therapy• 1st five days PPI (standard dose, bid)Amoxicillin (1 g, bid)• 2nd five days PPI (standard dose, bid)Clarihromycin (500 mg, bid)Metronidazole/Tinidazole (500 mg, bid)For 10 daysGisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.Indicated in clarithromycin or nitroimidazole resistance strainsNot indicated in dual clarithromycin & metronidazole resistance
  21. 21. Rationale of sequential therapySequential antibiotic administration not recommended“fear to promote drug resistance”.• Sequential administration1st five days Lower bacterial load in stomachPrevent selection of secondary Clari-RDrug rarely results in resistance (ampicillin)Eradiation rate at least 50%2nd five days Eradicate small population of viable organisms• Larger number of antibiotics (3 drugs)Gisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.
  22. 22. Sequential versus standard triple therapy15 RCTs – ITT – Random effect modelGisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.Eradication rate: 76.7% (75 – 79%) versus 91.7% (90 – 93%)
  23. 23. Limitations of sequential therapy• Low validation outside Italy• Small sample size: < 50 in some protocols• Low quality of studies: Jadad score ≥3 in 1/10 studies in MA1• Reduced compliance in clinical practice• Unsuitable for dual clarithromycin & nitroimidazole resistance• Unsuitable for penicillin allergy1 Tong JL et al. J Clin Pharm Ther. 2009 ; 34 : 41 – 53.2 Gisbert JP et al. J Clin Gastroenterol 2010 ; 44 : 313 – 325.
  24. 24. Concomitant therapy“Non-bismuth quadruple therapy”• PPI Standard dose, bid• Amoxicillin 1 g, bid• Clarithromycin 500 mg, bid• Metronidazole/Tinidazole 500 mg, bidRimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.For 10 – 14 daysNot indicated in high prevalence of Clari-R (> 20 – 30%)Not indicated in dual clarithromycin & metronidazole resistance
  25. 25. Concomitant therapy for treatment of H pyloriMeta-analysis – 15 RCTs (1723 pts – Random effectGisbert J P et al. Aliment Pharmacol Ther 2011 ; 34 : 604 – 617.
  26. 26. Sequential-concomitant therapy‘‘Hybrid therapy’’• 1st seven days PPI (standard dose, bid)Amoxicillin (1 g, bid)• 2nd seven days PPI (standard dose, bid)Amoxicillin (1 g, bid)Clarihromycin (500 mg, bid)Metronidazole/Tinidazole (500 mg, bid)Hsu, P. I. et al. Gastroenterology 2010 ; 138 (Suppl. 1), S111.For 14 daysTreatment success (117pts): 97% (ITT) – 99% (PP)High efficacy in dual clarithromycin & metronidazole resistance
  27. 27. Bismuth quadruple therapy (BMT)Underutilized in clinical practice• PPI Standard dose, bid• Bismuth subcitrate 420 mg, qid• Metronidazole/Tinidazole 500 mg, tid• Tetracycline 500 mg, qidFor 10 – 14 daysHighly effective: Eradication rate 92%Cost effective: Cost of 14-day course < $50Rimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.
  28. 28. Treatment regimen according to areas of Clari-RMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.1st linePPI-Amoxicillin-ClarithroBismuth quadrupleBismuth quadrupleSequential or ConcomitantRegion with low Clari-R< 20%Region with high Clari-R> 20%
  29. 29. Mégraud F. Presse Med. 2010 ; 39 : 815 – 822.Malfertheiner P et al. Gut 2012; 61: 646 – 664.Antibiotics Stopped for at least 4 weeksPPIs Stopped for 14 daysH2RA Stopped for 7 daysAntacids Not stoppedConfirmation of eradication for H. pyloriUBT & monoclonal stool testNo role for serology
  30. 30. Confirmation of eradication for H. pyloriNon-endoscopic methodsTests Sensitivity SpecificitySerologyELISA IgG70 – 90%70 – 90%Not to confirm eradicationUrea breath test 85 – 95% 85 – 95%Fecal antigen test“monoclonal”85 – 95% 85 – 95%WGO global guideline. J Clin Gastroenterol 2011 ; 45 : 383 – 388.Fischbach W et al. Dtsch Arztebl Int 2009 ; 106 : 801 – 8.
  31. 31. Treatment of H pylori-positive peptic ulcer• Uncomplicated DUProlongs PPI not recommended after HP treatment (Grade A)• GU & complicated DUProlongs PPI is recommended (Grade A)• Bleeding ulcerHP eradication started at introduction of oral feeding (Grade A)Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.
  32. 32. Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential-concomitant therapyBismuth quadruple therapy“legacy triple therapy”“five plus five day therapy”“non-bismuth quadruple therapy”“hybrid therapy”underutilized in practiceSecond line treatment (one treatment failure)Levofloxacin triple therapyThird line treatment (at least 2 treatment failures)Culture-guided therapyHigh-dose dual PPI therapyFurazolidone quadruple therapyRifabutin-based triple therapyRecommendedEmpiricalEmpiricalEmpirical – Last resort
  33. 33. Levofloxacin-based triple therapySecond line therapy• PPI Standard dose, bid• Amoxicillin 1 g, bid• Levofloxacin 500 mg, qdFor 10 – 14 daysRising rates of levofloxacin resistanceMalfertheiner P et al. Management of HP infection: the Maastricht IV/Florence consensus report.Gut 2012 ; 61: 646 – 664.
  34. 34. Treatment regimen according to areas of Clari-RRegion with low Clari-R< 20%Region with high Clari-R> 20%1st linePPI-Amoxicillin-ClarithroBismuth quadrupleBismuth quadrupleSequential or Concomitant2nd line*Bismuth quadruplePPI-Amoxicillin-LevofoxacinPPI-Amoxicillin-LevofoxacinMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.* Regimen should not include antibiotics given previously
  35. 35. Treatment of H. pylori infectionFirst line treatmentStandard triple therapySequential therapyConcomitant therapySequential-concomitant therapyBismuth quadruple therapy“legacy triple therapy”“five plus five day therapy”“non-bismuth quadruple therapy”“hybrid therapy”underutilized in practiceSecond line treatment (one treatment failure)Levofloxacin triple therapyThird line treatment (at least 2 treatment failures)Culture-guided therapyHigh-dose dual PPI therapyFurazolidone quadruple therapyRifabutin-based triple therapyRecommendedEmpiricalEmpiricalEmpirical – Last resort
  36. 36. Culture-guided therapyThird line therapy• PPI Standard dose, bid• Bismuth 2 tablets, qid• 1st antibiotic Selected by antimicrobial sensitivity tests• 2nd antibiotic Selected by antimicrobial sensitivity testsFor 10 – 14 daysMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.
  37. 37. Susceptibility testing• Culture & standard susceptibility testing (preferable)Practical for Clarithromycin & Levofloxacin resistanceMetronidazole susceptibility testing lacks reproducibility• Molecular tests (if culture not possible)Detect mutations in HP genome that result in resistanceRT PCR/nested PCR on gastric biopsies (or stool specimens)Practical for Clari-R & possibly fluoroquinolone resistance• Fluorescence in situ hybridization (FISH)On gastric biopsiesMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.
  38. 38. Fluorescence in situ hybridisation (FISH)Clarithromycin susceptibility of HP on gastric biopsyRimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.Correlate well with results of culture & susceptibility testingDetection of H. pyloriSusceptible & resistantIsothiocyanate-labeled probeClari-resistant onlyRhodamine-labeled probeClari-resistant: yellowClari-susceptible: greenCombined image
  39. 39. High-dose dual PPI therapyEmpirical third line therapy• PPI (high dose) Omeprazole 40 mg, qidorLansoprazole 30 mg, qid• Amoxicillin 500 mg, bidRimbara E & Graham DY. Nat Rev Gastroenterol Hepatol 2011 ; 8 : 79 – 88.For 14 daysStudies needed to confirm the success seen in Japan
  40. 40. Furazolidone-based quadruple therapyEmpirical third line therapy• PPI Standard dose, bid• Bismuth Standard dose, qid• Tetracyclin 500 mg, qid• Furazolidone 100 mg, tidGraham DY & Lu H. Saudi J Gastroenterol 2012 ; 18 : 1 – 2.For 10 – 14 days
  41. 41. Furazolidone• Produced commercially since 1955• Antibacterial & antiprotozoal in human & veterinary medicine• No longer marketed in US since 2005 (market too small)• No approved by the EMA1 for human medicine or animal use• Classified by the IARC2 as group 3 drug in 1998• Monamine oxidase inhibitor & may interact with food & drugs• Variable resistance: 1 – 25 % in Iran & 0 – 40% in China1 EMA: European Medicines Agency2 IARC: International Agency for Research on CancerGraham DY & Lu H. Saudi J Gastroenterol 2012 ; 18 : 1 – 2.Zullo A et al. Saudi J Gastroenterol 2012 ; 18 : 11 – 17.
  42. 42. Furazolidone-based quadruple therapySystematic reviewZullo A et al. Saudi J Gastroenterol 2012 ; 18 : 11 – 17.
  43. 43. Rifabutin-based triple therapyEmpirical third line therapy – Drug of last resort• PPI Standard dose, bid• Amoxicillin 1 g, bid• Rifabutin 150 mg, bidGisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.For 10 – 12 daysAdministered as rescue treatment without prior antibiogram
  44. 44. RifabutinRifamycin-S derivative• Indications Mycobacteria including MAC*Third line treatment of H pylori• Eradication 3rd line: 342 patients – 66% (55–77%)4th / 5th line: 95 patients – 70% (60–79%)• Resistance 2982 pts: 1.3% (95% CI: 0.9% to 1.7%)• Adverse effects Myelotoxicity: Most significant – RareRecovered of leucopenia in few days* MAC: Mycobacterium Avium-intracellulare ComplexGisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.
  45. 45. Rifabutin-based triple therapyEmpirical third line therapyGisbert J P et al. Aliment Pharmacol Ther 2012 ; 35 : 209 – 221.
  46. 46. 2nd line*Bismuth quadruplePPI-Amoxicillin-LevofoxacinPPI-Amoxicillin-LevofoxacinTreatment regimen according to areas of Clari-RMalfertheiner P et al. Gut 2012 ; 61: 646 – 664.* Regimen should not include antibiotics given previouslyRegion with low Clari-R< 20%Region with high Clari-R> 20%1st linePPI-Amoxicillin-ClarithroBismuth quadrupleBismuth quadrupleSequential or Concomitant3rd line Based on susceptibility testing only
  47. 47. Malfertheiner P et al. Gut 2012 ; 61: 646 – 664.* Regimen should not include antibiotics given previouslyTreatment in patients with penicillin allergyRelatively common subgroup of patients1st linePPI-Clarithro-Metronidazole Bismuth quadruple2nd line*PPI – Clarithromycin – LevofoxacinRegion with low levofloxacin resistanceRegion with low Clari-R< 20%Region with high Clari-R> 20%
  48. 48. Cautions associated with anti-HP antimicrobials• Nitroimidazole Carcinogenicity (Group 2B – IARC)Antibuse-like reaction• Furazolidone Carcinogenicity (Group 3 – IARC)Monamine oxidase inhibitorAvoid some food & drugs• Fluoroquinolone Tendinitis & tendon rupture especially:> 60 year, organ transplants, steroids• Rifabutin Induces CYP3A enzymesLast resort Interacts with long list of drugsIncreasing resistance of mycobacteria* IARC: International Agency for Research on CancerGraham DY & Fischbach L. Gut 2010 ; 59 : 1143 – 1153.
  49. 49. General recommendations for H. pylori treatment• 1st line therapy Avoid CLA if given for any indicationAvoid LEV if given for any indicationUse 4-drug treatment: sequential, bismuth,.Use higher doses of drugsUse 14 day duration• 2nd line therapy Do not reuse same drugs• 3rd line therapy Use culture-guided therapy if availableRifabutin-based therapy as last resortGraham DY & Fischbach L. Gut 2010 ; 59 : 1143 – 1153.
  50. 50. References
  51. 51. Thank You

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