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__NOTOC__
__NOTOC____NOEDITSECTION__
{{Peptic ulcer}}
{{Peptic ulcer}}
{{CMG}}
{{CMG}}; Gerald Chi, M.D.


==Overview==
==Overview==
Eradication of ''[[Helicobacter pylori]]'' with antimicrobial agents is indicated for patients with [[gastric ulcer|gastric]] or [[duodenal ulcer|duodenal peptic ulceration]] who are colonized with ''[[Helicobacter pylori]]'' and patients with [[MALT lymphoma]].  Eradication therapy should also be considered for patients with [[immune thrombocytopenic purpura]] who are ''[[H. pylori]]'' positive or patients who have undergone resection for early-stage [[gastric cancer]].  The use of antibiotics is discouraged in asymptomatic carriers.
Eradication of ''[[Helicobacter pylori]]'' with antimicrobial agents is indicated for patients with [[gastric ulcer|gastric]] or [[duodenal ulcer|duodenal peptic ulceration]] who are colonized with ''[[Helicobacter pylori]]'' and patients with [[MALT lymphoma]].  Eradication therapy should also be considered for patients with [[immune thrombocytopenic purpura]] who are ''[[H. pylori]]'' positive or patients who have undergone resection for early-stage [[gastric cancer]].  The use of antibiotics is discouraged in asymptomatic carriers.  


==Medical Therapy==
==Medical Therapy==
 
{| style="float: right; width: 300px; margin: 5px 10px;"
===Diagnostic testing===
! style="font-size: 85%; background: #545454; color: #F8F8FF; padding: 5px 10px;" | Countries with a reported prevalence < 15% of ''H. pylori'' resistance to clarithromycin
The American Journal of Gastroenterology guidelines recommend that '''[[endoscopy]]''' should be performed to rule out [[peptic ulcer disease]], esophagogastric [[malignancy]], and other rare upper gastrointestinal tract disease in the following settings:
|-
* [[Dyspeptic]] patients more than 55 years old {{or2}}
! style="font-size: 85%; background: #DCDCDC;" | Europe
* [[Dyspeptic]] patients with <u>alarm features</u>
:* [[Bleeding]]
:* [[Anemia]]
:* [[Early satiety]]
:* Unexplained [[weight loss]] (> 10% body weight)
:* Progressive [[dysphagia]]
:* [[Odynophagia]]
:* Persistent [[vomiting]]
:* A family history of gastrointestinal cancer
:* Previous esophagogastric [[malignancy]]
:* Previous documented [[peptic ulcer]], [[lymphadenopathy]], or an abdominal mass
 
In patients aged 55 years or younger with no alarm features, two management options may be considered:
* '''Test-and-treat strategy''' using a validated noninvasive test (urea breathing test or stool antigen test) for ''[[H. pylori]]'' and a trial of acid suppression if eradication is successful but symptoms do not resolve: preferable in populations with a moderate to high prevalence of ''[[H. pylori]]'' infection (≥ 10%)
* An empiric trial of acid suppression with a '''[[proton pump inhibitor]] for 4–8 weeks''': preferable in low prevalence situations
 
Repeat [[endoscopy]] is not recommended once a firm diagnosis of functional [[dyspepsia]] has been established, unless new symptoms or alarm features develop.<ref>{{Cite journal| doi = 10.1111/j.1572-0241.2005.00225.x| issn = 0002-9270| volume = 100| issue = 10| pages = 2324–2337| last1 = Talley| first1 = Nicholas J.| last2 = Vakil| first2 = Nimish| last3 = Practice Parameters Committee of the American College of Gastroenterology| title = Guidelines for the management of dyspepsia| journal = The American Journal of Gastroenterology| date = 2005-10| pmid = 16181387}}</ref>
 
===Treatment strategies===
* The use of high-dose (twice a day) '''[[PPI|proton pump inhibitor (PPI)]]''' increases the efficacy of triple therapy.
* In areas of low clarithromycin resistance, '''[[clarithromycin]]-containing treatments (PCA or PCM)''' are recommended for first-line empirical treatment.  '''[[Bismuth]]-containing quadruple treatment''' is also an alternative.
* In areas of high clarithromycin resistance, '''[[bismuth]]-containing quadruple treatment''' is recommended for first-line empirical treatment.  If this regimen is not available, '''sequential treatment''' is recommended.
* Extending the duration of PPI-clarithromycin-containing triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
* After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple therapy of levofloxacin-containing triple therapy are recommended.
* After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.
* The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.
 
 
* '''Low''' clarithromycin '''resistance''' areas '''(<15%)''':<ref name="pmid22491499">{{cite journal| author=Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F et al.| title=Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. | journal=Gut | year= 2012 | volume= 61 | issue= 5 | pages= 646-64 | pmid=22491499 | doi=10.1136/gutjnl-2012-302084 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22491499  }} </ref>
** In areas of '''low resistance''' the '''PPI-clarithromycin-containing triple therapy''' is recommended as the first-line treatment as well as '''bismuth-containing quadruple therapy'''.
** In areas of '''low resistance''' after '''failure of a PPI-clarithromycin-containing treatment''', either a '''bismuth-containing quadruple therapy''' or '''levofloxacin-containing triple therapy is recommended'''.
* '''High''' clarithromycin '''resistance''' areas '''(≥15%)''':<ref name="pmid22491499">{{cite journal| author=Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F et al.| title=Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. | journal=Gut | year= 2012 | volume= 61 | issue= 5 | pages= 646-64 | pmid=22491499 | doi=10.1136/gutjnl-2012-302084 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22491499  }} </ref>
** In areas of '''high resistance''', '''bismuth-containing quadruple therapy''' is recommended as the first-line treatment.
** In areas of '''high resistance''' after '''failure of bismuth containing quadruple therapy''', '''Levofloxacin containing triple therapy''' is recommended.
* If the '''second-line treatment''' fails, the antibiotic therapy should guided by '''antimicrobial susceptibility''' testing.<ref name="pmid22491499">{{cite journal| author=Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F et al.| title=Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. | journal=Gut | year= 2012 | volume= 61 | issue= 5 | pages= 646-64 | pmid=22491499 | doi=10.1136/gutjnl-2012-302084 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22491499  }} </ref>
* FDA approved first line regimens duration:<ref name="pmid17608775">{{cite journal| author=Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology| title=American College of Gastroenterology guideline on the management of Helicobacter pylori infection. | journal=Am J Gastroenterol | year= 2007 | volume= 102 | issue= 8 | pages= 1808-25 | pmid=17608775 | doi=10.1111/j.1572-0241.2007.01393.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17608775  }} </ref>
** Triple therapy: 7 days (10 days if [[rabeprazole]] is used).
** Quadruple therapy: 4 weeks.
* Patients who have had a previous ''H. pylori'' associated ulcer or gastric MALT lymphoma or who have had surgical resection for early gastric cancer, confirmation tests for eradication of ''H. pylori'' infection should be done.<ref name="pmid20427808">{{cite journal| author=McColl KE| title=Clinical practice. Helicobacter pylori infection. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 17 | pages= 1597-604 | pmid=20427808 | doi=10.1056/NEJMcp1001110 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20427808  }} </ref>
* The best nonendoscopic test to confirm eradication of ''H. pylori'' infection is the urea breathing test.<ref name="pmid17608775">{{cite journal| author=Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology| title=American College of Gastroenterology guideline on the management of Helicobacter pylori infection. | journal=Am J Gastroenterol | year= 2007 | volume= 102 | issue= 8 | pages= 1808-25 | pmid=17608775 | doi=10.1111/j.1572-0241.2007.01393.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17608775  }} </ref>
* Testing to prove ''H. pylori'' eradication is most accurate if performed 4 weeks after the completion of the therapy.<ref name="pmid20427808">{{cite journal| author=McColl KE| title=Clinical practice. Helicobacter pylori infection. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 17 | pages= 1597-604 | pmid=20427808 | doi=10.1056/NEJMcp1001110 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20427808  }} </ref>
 
{| style="border: 2px solid #DCDCDC; font-size: 90%; width: 80%;"
|+ '''Countries with a reported prevalence <15% of ''H. pylori'' resistance to clarithromycin'''<ref name="pmid15306603">{{cite journal| author=Mégraud F| title=H pylori antibiotic resistance: prevalence, importance, and advances in testing. | journal=Gut | year= 2004 | volume= 53 | issue= 9 | pages= 1374-84 | pmid=15306603 | doi=10.1136/gut.2003.022111 | pmc=PMC1774187 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15306603  }} </ref><ref name="pmid15207062">{{cite journal| author=Duck WM, Sobel J, Pruckler JM, Song Q, Swerdlow D, Friedman C et al.| title=Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. | journal=Emerg Infect Dis | year= 2004 | volume= 10 | issue= 6 | pages= 1088-94 | pmid=15207062 | doi=10.3201/eid1006.030744 | pmc=PMC3323181 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15207062  }} </ref><ref name="pmid21188333">{{cite journal| author=De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C et al.| title=Worldwide H. pylori antibiotic resistance: a systematic review. | journal=J Gastrointestin Liver Dis | year= 2010 | volume= 19 | issue= 4 | pages= 409-14 | pmid=21188333 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21188333  }} </ref><ref name="pmid20014902">{{cite journal| author=Boyanova L, Mitov I| title=Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. | journal=Expert Rev Anti Infect Ther | year= 2010 | volume= 8 | issue= 1 | pages= 59-70 | pmid=20014902 | doi=10.1586/eri.09.113 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20014902  }} </ref>
! style="background: #DCDCDC;" | Europe
! style="background: #DCDCDC;" | North America
! style="background: #DCDCDC;" | South America
! style="background: #DCDCDC;" | Middle East
! style="background: #DCDCDC;" | Far East
|-
|-
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
| style="font-size: 85%; background: #F5F5F5;" |
* Belgium (3%)
* Belgium (3%)
* Croatia (8.2%)
* Croatia (8.2%)
Line 72: Line 23:
* Sweden (2.9%)
* Sweden (2.9%)
* UK (8.3–12.7%)
* UK (8.3–12.7%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | North America
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Canada (12%)
* Canada (12%)
* USA (10.6–12.2%)<sup>†</sup>
* USA (10.6–12.2%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | South America
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Brazil (9.8%)
* Brazil (9.8%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | Middle East
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Israel (8.2%)
* Israel (8.2%)
* Saudi Arabia (4%)
* Saudi Arabia (4%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | Far East
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Bangladesh (10%)
* Bangladesh (10%)
* Hong Kong (4.5%)
* Hong Kong (4.5%)
* Korea (14%)
* Korea (14%)
* Malaysia (2.1%
* Malaysia (2.1%)
* New Zealand (11%)
* New Zealand (11%)
|}
<SMALL><sup>†</sup> There is a reported prevalence of 15% in the Northeast of the US.</SMALL>
{| style="border: 2px solid #DCDCDC; font-size: 90%; width: 66%;"
|+ '''Countries with a reported prevalence ≥15% of H. pylori resistance to clarithromycin'''<ref name="pmid15306603">{{cite journal| author=Mégraud F| title=H pylori antibiotic resistance: prevalence, importance, and advances in testing. | journal=Gut | year= 2004 | volume= 53 | issue= 9 | pages= 1374-84 | pmid=15306603 | doi=10.1136/gut.2003.022111 | pmc=PMC1774187 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15306603  }} </ref><ref name="pmid15207062">{{cite journal| author=Duck WM, Sobel J, Pruckler JM, Song Q, Swerdlow D, Friedman C et al.| title=Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. | journal=Emerg Infect Dis | year= 2004 | volume= 10 | issue= 6 | pages= 1088-94 | pmid=15207062 | doi=10.3201/eid1006.030744 | pmc=PMC3323181 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15207062  }} </ref><ref name="pmid21188333">{{cite journal| author=De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C et al.| title=Worldwide H. pylori antibiotic resistance: a systematic review. | journal=J Gastrointestin Liver Dis | year= 2010 | volume= 19 | issue= 4 | pages= 409-14 | pmid=21188333 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21188333  }} </ref><ref name="pmid20014902">{{cite journal| author=Boyanova L, Mitov I| title=Geographic map and evolution of primary Helicobacter pylori resistance to antibacterial agents. | journal=Expert Rev Anti Infect Ther | year= 2010 | volume= 8 | issue= 1 | pages= 59-70 | pmid=20014902 | doi=10.1586/eri.09.113 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20014902  }} </ref>
! style="background: #DCDCDC;" | Europe
! style="background: #DCDCDC;" | North America
! style="background: #DCDCDC;" | Middle East
! style="background: #DCDCDC;" | Far East
|-
|-
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
! style="font-size: 85%; background: #545454; color: #F8F8FF; padding: 5px 10px;" | Countries with a reported prevalence ≥ 15% of ''H. pylori'' resistance to clarithromycin
|-
! style="font-size: 85%; background: #DCDCDC;" | Europe
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Bulgaria (18.4%)
* Bulgaria (18.4%)
* France (20%)  
* France (20%)  
Line 103: Line 61:
* Spain (49.2%)
* Spain (49.2%)
* Turkey (48.2%)
* Turkey (48.2%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | South America
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Mexico (25%)
* Mexico (25%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | Middle East
|-
| style="font-size: 85%; background: #F5F5F5;" |
* Iran (17%)
* Iran (17%)
| style="background: #F5F5F5; padding: 0 10px; width: 20%;" valign=top |
|-
! style="font-size: 85%; background: #DCDCDC;" | Far East
|-
| style="font-size: 85%; background: #F5F5F5;" |
* China (18%)
* China (18%)
* India (33%)
* India (33%)
* Japan (27.7%)
* Japan (27.7%)
* Taiwan (13.5%)
|}
|}
===Diagnostic testing===
The American Journal of Gastroenterology guidelines recommend that '''endoscopy''' should be performed to rule out [[peptic ulcer disease]], esophagogastric [[malignancy]], and other rare upper gastrointestinal tract disease in the following settings:
* [[Dyspeptic]] patients <u>more than 55 years old</u> {{or2}}
* [[Dyspeptic]] patients with <u>alarm features</u>
:* [[Bleeding]]
:* [[Anemia]]
:* [[Early satiety]]
:* Unexplained [[weight loss]] (> 10% body weight)
:* Progressive [[dysphagia]]
:* [[Odynophagia]]
:* Persistent [[vomiting]]
:* A family history of gastrointestinal cancer
:* Previous esophagogastric [[malignancy]]
:* Previous documented [[peptic ulcer]], [[lymphadenopathy]], or an abdominal mass
In patients aged 55 years or younger with no alarm features, two management options may be considered:
* '''Test-and-treat strategy''' using a validated noninvasive test (urea breathing test or stool antigen test) for ''[[H. pylori]]'' and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of ''[[H. pylori]]'' infection (≥ 10%)
* '''Empiric trial of acid suppression''' with a [[proton pump inhibitor]] for 4–8 weeks – preferable in low prevalence situations
Repeat [[endoscopy]] is not recommended once a firm diagnosis of functional [[dyspepsia]] has been established, unless new symptoms or alarm features develop.<ref>{{Cite journal| doi = 10.1111/j.1572-0241.2005.00225.x| issn = 0002-9270| volume = 100| issue = 10| pages = 2324–2337| last1 = Talley| first1 = Nicholas J.| last2 = Vakil| first2 = Nimish| last3 = Practice Parameters Committee of the American College of Gastroenterology| title = Guidelines for the management of dyspepsia| journal = The American Journal of Gastroenterology| date = 2005-10| pmid = 16181387}}</ref>  Testing to prove ''[[H. pylori]]'' eradication is most accurate if performed 4 weeks after the completion of therapy.<ref>{{Cite journal| doi = 10.1136/gutjnl-2012-302084| issn = 1468-3288| volume = 61| issue = 5| pages = 646–664| last1 = Malfertheiner| first1 = Peter| last2 = Megraud| first2 = Francis| last3 = O'Morain| first3 = Colm A.| last4 = Atherton| first4 = John| last5 = Axon| first5 = Anthony T. R.| last6 = Bazzoli| first6 = Franco| last7 = Gensini| first7 = Gian Franco| last8 = Gisbert| first8 = Javier P.| last9 = Graham| first9 = David Y.| last10 = Rokkas| first10 = Theodore| last11 = El-Omar| first11 = Emad M.| last12 = Kuipers| first12 = Ernst J.| last13 = European Helicobacter Study Group| title = Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report| journal = Gut| date = 2012-05| pmid = 22491499}}</ref>
===Treatment strategies===
* The use of high-dose (twice a day) [[PPI|proton pump inhibitor (PPI)]] increases the efficacy of triple therapy.
: [[Lansoprazole]] 30 mg q12h {{or2}}
: [[Omeprazole]] 20 mg q12h {{or2}}
: [[Esomeprazole]] 40 mg q24h {{or2}}
: [[Rabeprazole]] 20 mg q12h
* In areas of low clarithromycin resistance, '''[[clarithromycin]]-containing treatments (PCA or PCM)''' are recommended for first-line empirical treatment.  '''[[Bismuth]]-containing quadruple treatment''' is also an alternative.
* In areas of high clarithromycin resistance, '''[[bismuth]]-containing quadruple treatment''' is recommended for first-line empirical treatment.  If this regimen is not available, '''sequential treatment''' is recommended.
* Extending the duration of triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
* After failure of a PPI-clarithromycin containing therapy, either a '''[[bismuth]]-containing quadruple treatment''' or '''[[levofloxacin]]-containing triple therapy (PLA)''' is recommended.
* After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.
* The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.<ref>{{Cite journal| doi = 10.1136/gutjnl-2012-302084| issn = 1468-3288| volume = 61| issue = 5| pages = 646–664| last1 = Malfertheiner| first1 = Peter| last2 = Megraud| first2 = Francis| last3 = O'Morain| first3 = Colm A.| last4 = Atherton| first4 = John| last5 = Axon| first5 = Anthony T. R.| last6 = Bazzoli| first6 = Franco| last7 = Gensini| first7 = Gian Franco| last8 = Gisbert| first8 = Javier P.| last9 = Graham| first9 = David Y.| last10 = Rokkas| first10 = Theodore| last11 = El-Omar| first11 = Emad M.| last12 = Kuipers| first12 = Ernst J.| last13 = European Helicobacter Study Group| title = Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report| journal = Gut| date = 2012-05| pmid = 22491499}}</ref>


==Eradication Therapy for ''Helicobacter pylori'' Infection==
==Eradication Therapy for ''Helicobacter pylori'' Infection==


===First-line therapies===
===First-line therapies===
{{rx|Triple therapy (PCA or PCM)}}
{{rx|Triple therapy (PCA or PCM regimen)}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 7–14 days {{and}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 7–14 days {{and}}
* '''[[Clarithromycin]]''' (500 mg twice daily) for 7–14 days {{and}}
* '''[[Clarithromycin]]''' (500 mg twice daily) for 7–14 days {{and}}
Line 130: Line 130:
{{rx|Sequential therapy}}
{{rx|Sequential therapy}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 5 days {{and}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 5 days {{and}}
* '''[[Amoxicillin]]''' (1 g twice times daily) for 5 days<BR><span style="text-indent: 50px;">''Followed by''</span>
* '''[[Amoxicillin]]''' (1 g twice times daily) for 5 days<BR><span style="text-indent: 50px;">'''<u>FOLLOWED BY</u>'''</span>
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for another 5 days {{and}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for another 5 days {{and}}
* '''[[Clarithromycin]]''' (500 mg twice daily) for another 5 days {{and}}
* '''[[Clarithromycin]]''' (500 mg twice daily) for another 5 days {{and}}
Line 137: Line 137:


===Second-line therapies===
===Second-line therapies===
{{rx|Triple therapy (PMA)}}
{{rx|Triple therapy (PLA regimen)}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 10 days {{and}}
* '''[[Levofloxacin]]''' (500 mg twice daily) for 10 days {{and}}
* '''[[Amoxicillin]]''' (1 g twice daily) for 10 days
</li>
{{rx|Triple therapy (PMA regimen)}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 7–14 days {{and}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 7–14 days {{and}}
* '''[[Metronidazole]]''' (250 mg four times daily) for 7–14 days {{and}}
* '''[[Metronidazole]]''' (250 mg four times daily) for 7–14 days {{and}}
* '''[[Amoxicillin]]''' (1 g twice daily) for 7–14 days
* '''[[Amoxicillin]]''' (1 g twice daily) for 7–14 days
</li>
</li>
{{rx|Triple therapy (PLA)}}
{{rx|Triple therapy (PRA regimen)}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 10 days {{and}}
* '''[[Levofloxacin]]''' (500 mg twice daily) for 10 days {{and}}
* '''[[Amoxicillin]]''' (1 g twice daily) for 10 days
</li>
{{rx|Triple therapy (PRA)}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 10 days {{and}}
* '''[[Proton pump inhibitor]]''' (standard dose twice daily) for 10 days {{and}}
* '''[[Rifabutin]]''' (150–300 mg/day) for 10 days {{and}}
* '''[[Rifabutin]]''' (150–300 mg/day) for 10 days {{and}}
* '''[[Amoxicillin]]''' (1 g twice daily) for 10 days
* '''[[Amoxicillin]]''' (1 g twice daily) for 10 days
</li>
</li>
==Algorithm for the Approach to Dyspepsia==
<div style="font-size: 80%;">
{{Familytree/start}}
{{Familytree|boxstyle=border: 0;| | | | | | A01 | | | | | | | | | | |A01={{F1|Age ≥ 55 or ⊕ alarm features?}}}}
{{Familytree|boxstyle=border: 0;| |,|-|-|-|-|^|-|-|-|-|.| | | | | | |}}
{{Familytree|boxstyle=border: 0;| B01 | | | | | | | | B02 | | | | | |B01={{F1|YES}}|B02={{F1|NO}}}}
{{Familytree|boxstyle=border: 0;| |!| | | | | | | | | |!| | | | | | |}}
{{Familytree|boxstyle=border: 0;| C01 | | | | | | | | C02 | | | | | |C01={{F2|Endoscopy}}|C02={{F1|''H. pylori'' prevalence?}}}}
{{Familytree|boxstyle=border: 0;| |!| | | | |,|-|-|-|-|^|-|-|-|-|.| |}}
{{Familytree|boxstyle=border: 0;| |!| | | | D01 | | | | | | | | D02 |D01={{F1|High}}|D02={{F1|Low}}}}
{{Familytree|boxstyle=border: 0;| |!| | | | |!| | | | | | | | | |!| |}}
{{Familytree|boxstyle=border: 0;| |!| | | | E01 | | | | | | | | E02 |E01={{F2|Test-and-treat strategy}}|E02={{F2|Acid suppression trial}}}}
{{Familytree|boxstyle=border: 0;| |`|-|-|-|-|+|-|-|-|-|-|-|-|-|-|'| |}}
{{Familytree|boxstyle=border: 0;| | | | | | F01 | | | | | | | | | | |F01={{F1|If treatment is indicated}}}}
{{Familytree|boxstyle=border: 0;| |,|-|-|-|-|^|-|-|-|-|.| | | | | | |}}
{{Familytree|boxstyle=border: 0;| G01 | | | | | | | | G02 | | | | | |G01={{F1|Clarithromycin resistance ≥ 15%}}|G02={{F1|Clarithromycin resistance < 15%}}}}
{{Familytree|boxstyle=border: 0;| |!| | | | | | | | | |!| | | | | | |}}
{{Familytree|boxstyle=border: 0;| H01 | | | | | | | | H02 | | | | | |H01={{F2|Quadruple or sequential therapy}}|H02={{F2|PCA or PCM regimen}}}}
{{Familytree|boxstyle=border: 0;| |!| | | | | | | | | |!| | | | | | |}}
{{Familytree|boxstyle=border: 0;| I01 | | | | | | | | I02 | | | | | |I01={{F2|PLA regimen}}|I02={{F2|Quadruple therapy or PLA regimen}}}}
{{Familytree|boxstyle=border: 0;| |`|-|-|-|-|v|-|-|-|-|'| | | | | | |}}
{{Familytree|boxstyle=border: 0;| | | | | | F01 | | | | | | | | | | |F01={{F1|Adjust Rx per susceptibility test}}}}
{{Familytree/end}}
</div>


==Contraindicated Medications==
==Contraindicated Medications==
Line 161: Line 186:
* American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.<ref>{{Cite journal| doi = 10.1016/j.gie.2010.12.003| issn = 1097-6779| volume = 74| issue = 1| pages = 13–21| last1 = ASGE Standards of Practice Committee| last2 = Fukami| first2 = Norio| last3 = Anderson| first3 = Michelle A.| last4 = Khan| first4 = Khalid| last5 = Harrison| first5 = M. Edwyn| last6 = Appalaneni| first6 = Vasudhara| last7 = Ben-Menachem| first7 = Tamir| last8 = Decker| first8 = G. Anton| last9 = Fanelli| first9 = Robert D.| last10 = Fisher| first10 = Laurel| last11 = Ikenberry| first11 = Steven O.| last12 = Jain| first12 = Rajeev| last13 = Jue| first13 = Terry L.| last14 = Krinsky| first14 = Mary Lee| last15 = Maple| first15 = John T.| last16 = Sharaf| first16 = Ravi N.| last17 = Dominitz| first17 = Jason A.| title = The role of endoscopy in gastroduodenal obstruction and gastroparesis| journal = Gastrointestinal Endoscopy| date = 2011-07| pmid = 21704805}}</ref>
* American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.<ref>{{Cite journal| doi = 10.1016/j.gie.2010.12.003| issn = 1097-6779| volume = 74| issue = 1| pages = 13–21| last1 = ASGE Standards of Practice Committee| last2 = Fukami| first2 = Norio| last3 = Anderson| first3 = Michelle A.| last4 = Khan| first4 = Khalid| last5 = Harrison| first5 = M. Edwyn| last6 = Appalaneni| first6 = Vasudhara| last7 = Ben-Menachem| first7 = Tamir| last8 = Decker| first8 = G. Anton| last9 = Fanelli| first9 = Robert D.| last10 = Fisher| first10 = Laurel| last11 = Ikenberry| first11 = Steven O.| last12 = Jain| first12 = Rajeev| last13 = Jue| first13 = Terry L.| last14 = Krinsky| first14 = Mary Lee| last15 = Maple| first15 = John T.| last16 = Sharaf| first16 = Ravi N.| last17 = Dominitz| first17 = Jason A.| title = The role of endoscopy in gastroduodenal obstruction and gastroparesis| journal = Gastrointestinal Endoscopy| date = 2011-07| pmid = 21704805}}</ref>
* American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.<ref>{{Cite journal| doi = 10.1161/CIRCULATIONAHA.108.191087| issn = 1524-4539| volume = 118| issue = 18| pages = 1894–1909| last1 = Bhatt| first1 = Deepak L.| last2 = Scheiman| first2 = James| last3 = Abraham| first3 = Neena S.| last4 = Antman| first4 = Elliott M.| last5 = Chan| first5 = Francis K. L.| last6 = Furberg| first6 = Curt D.| last7 = Johnson| first7 = David A.| last8 = Mahaffey| first8 = Kenneth W.| last9 = Quigley| first9 = Eamonn M.| last10 = American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents| title = ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents| journal = Circulation| date = 2008-10-28| pmid = 18836135}}</ref>
* American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.<ref>{{Cite journal| doi = 10.1161/CIRCULATIONAHA.108.191087| issn = 1524-4539| volume = 118| issue = 18| pages = 1894–1909| last1 = Bhatt| first1 = Deepak L.| last2 = Scheiman| first2 = James| last3 = Abraham| first3 = Neena S.| last4 = Antman| first4 = Elliott M.| last5 = Chan| first5 = Francis K. L.| last6 = Furberg| first6 = Curt D.| last7 = Johnson| first7 = David A.| last8 = Mahaffey| first8 = Kenneth W.| last9 = Quigley| first9 = Eamonn M.| last10 = American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents| title = ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents| journal = Circulation| date = 2008-10-28| pmid = 18836135}}</ref>
* The European Helicobacter Study Group (EHSG) – Management of ''Helicobacter pylori'' infection.<ref>{{cite journal| author=Malfertheiner P, Megraud F, O'Morain CA, Atherton J, Axon AT, Bazzoli F et al.| title=Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. | journal=Gut | year= 2012 | volume= 61 | issue= 5 | pages= 646-64 | pmid=22491499 | doi=10.1136/gutjnl-2012-302084 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22491499  }}</ref>
* The European Helicobacter Study Group (EHSG) – Management of ''Helicobacter pylori'' infection.<ref>{{Cite journal| doi = 10.1136/gutjnl-2012-302084| issn = 1468-3288| volume = 61| issue = 5| pages = 646–664| last1 = Malfertheiner| first1 = Peter| last2 = Megraud| first2 = Francis| last3 = O'Morain| first3 = Colm A.| last4 = Atherton| first4 = John| last5 = Axon| first5 = Anthony T. R.| last6 = Bazzoli| first6 = Franco| last7 = Gensini| first7 = Gian Franco| last8 = Gisbert| first8 = Javier P.| last9 = Graham| first9 = David Y.| last10 = Rokkas| first10 = Theodore| last11 = El-Omar| first11 = Emad M.| last12 = Kuipers| first12 = Ernst J.| last13 = European Helicobacter Study Group| title = Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report| journal = Gut| date = 2012-05| pmid = 22491499}}</ref>


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Primary care]]

Latest revision as of 06:38, 28 July 2020

Peptic ulcer Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Gerald Chi, M.D.

Overview

Eradication of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal peptic ulceration who are colonized with Helicobacter pylori and patients with MALT lymphoma. Eradication therapy should also be considered for patients with immune thrombocytopenic purpura who are H. pylori positive or patients who have undergone resection for early-stage gastric cancer. The use of antibiotics is discouraged in asymptomatic carriers.

Medical Therapy

Countries with a reported prevalence < 15% of H. pylori resistance to clarithromycin
Europe
  • Belgium (3%)
  • Croatia (8.2%)
  • Denmark (11%)
  • Finland (2%)
  • Germany (2.2–4%)
  • Italy (North) (1.8%)
  • Ireland (8.8%)
  • Netherlands (1.7%)
  • Sweden (2.9%)
  • UK (8.3–12.7%)
North America
  • Canada (12%)
  • USA (10.6–12.2%)
South America
  • Brazil (9.8%)
Middle East
  • Israel (8.2%)
  • Saudi Arabia (4%)
Far East
  • Bangladesh (10%)
  • Hong Kong (4.5%)
  • Korea (14%)
  • Malaysia (2.1%)
  • New Zealand (11%)
Countries with a reported prevalence ≥ 15% of H. pylori resistance to clarithromycin
Europe
  • Bulgaria (18.4%)
  • France (20%)
  • Italy (central) (23.4%)
  • Portugal (22%)
  • Spain (49.2%)
  • Turkey (48.2%)
South America
  • Mexico (25%)
Middle East
  • Iran (17%)
Far East
  • China (18%)
  • India (33%)
  • Japan (27.7%)

Diagnostic testing

The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:

In patients aged 55 years or younger with no alarm features, two management options may be considered:

  • Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
  • Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations

Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop.[1] Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.[2]

Treatment strategies

Lansoprazole 30 mg q12h
OR
Omeprazole 20 mg q12h
OR
Esomeprazole 40 mg q24h
OR
Rabeprazole 20 mg q12h
  • In areas of low clarithromycin resistance, clarithromycin-containing treatments (PCA or PCM) are recommended for first-line empirical treatment. Bismuth-containing quadruple treatment is also an alternative.
  • In areas of high clarithromycin resistance, bismuth-containing quadruple treatment is recommended for first-line empirical treatment. If this regimen is not available, sequential treatment is recommended.
  • Extending the duration of triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
  • After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple treatment or levofloxacin-containing triple therapy (PLA) is recommended.
  • After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.
  • The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.[3]

Eradication Therapy for Helicobacter pylori Infection

First-line therapies

    • Second-line therapies

    • Algorithm for the Approach to Dyspepsia

     
     
     
     
     
    		Age ≥ 55 or ⊕ alarm features?
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    YES
     
     
     
     
     
     
     
    		NO
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Endoscopy
     
     
     
     
     
     
     
    		H. pylori prevalence?
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    		High
     
     
     
     
     
     
     
    		Low
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    		Test-and-treat strategy
     
     
     
     
     
     
     
    		Acid suppression trial
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    		If treatment is indicated
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Clarithromycin resistance ≥ 15%
     
     
     
     
     
     
     
    		Clarithromycin resistance < 15%
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Quadruple or sequential therapy
     
     
     
     
     
     
     
    		PCA or PCM regimen
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    PLA regimen
     
     
     
     
     
     
     
    		Quadruple therapy or PLA regimen
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    		Adjust Rx per susceptibility test
     
     
     
     
     
     
     
     
     
     

    Contraindicated Medications

    Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications:

    Guidelines and Resources

    • American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia.[4]
    • American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia.[5]
    • American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.[6]
    • American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.[7]
    • The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection.[8]

    References

    1. ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in: |date= (help)
    2. ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help)
    3. ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help)
    4. ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in: |date= (help)
    5. ↑ Ikenberry, Steven O.; Harrison, M. Edwyn; Lichtenstein, David; Dominitz, Jason A.; Anderson, Michelle A.; Jagannath, Sanjay B.; Banerjee, Subhas; Cash, Brooks D.; Fanelli, Robert D.; Gan, Seng-Ian; Shen, Bo; Van Guilder, Trina; Lee, Kenneth K.; Baron, Todd H.; ASGE STANDARDS OF PRACTICE COMMITTEE (2007-12). "The role of endoscopy in dyspepsia". Gastrointestinal Endoscopy. 66 (6): 1071–1075. doi:10.1016/j.gie.2007.07.007. ISSN 0016-5107. PMID 18028927. Check date values in: |date= (help)
    6. ↑ ASGE Standards of Practice Committee; Fukami, Norio; Anderson, Michelle A.; Khan, Khalid; Harrison, M. Edwyn; Appalaneni, Vasudhara; Ben-Menachem, Tamir; Decker, G. Anton; Fanelli, Robert D.; Fisher, Laurel; Ikenberry, Steven O.; Jain, Rajeev; Jue, Terry L.; Krinsky, Mary Lee; Maple, John T.; Sharaf, Ravi N.; Dominitz, Jason A. (2011-07). "The role of endoscopy in gastroduodenal obstruction and gastroparesis". Gastrointestinal Endoscopy. 74 (1): 13–21. doi:10.1016/j.gie.2010.12.003. ISSN 1097-6779. PMID 21704805. Check date values in: |date= (help)
    7. ↑ Bhatt, Deepak L.; Scheiman, James; Abraham, Neena S.; Antman, Elliott M.; Chan, Francis K. L.; Furberg, Curt D.; Johnson, David A.; Mahaffey, Kenneth W.; Quigley, Eamonn M.; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (2008-10-28). "ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents". Circulation. 118 (18): 1894–1909. doi:10.1161/CIRCULATIONAHA.108.191087. ISSN 1524-4539. PMID 18836135.
    8. ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help)
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