Helicobacter pylori: Difference between revisions

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Helicobacter pylori
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==Background==
* Slow-growing [[Has Gram stain::Gram-negative]] microaerophilic [[Has shape::bacillus]] with a curve, gull-wing, or spiral appearance
 
* [[Has oxidase test::Oxidase-positive]] and [[Has urease test::urease-positive]]
 
* Major cause of peptic ulcer disease and gastric cancer
 
   
 
*Slow-growing [[Stain::Gram-negative]] microaerophilic [[Shape::bacillus]] with a curve, gull-wing, or spiral appearance
  +
*Oxidase-[[Oxidase::positive]] and urease-[[Urease::positive]]
 
*Major cause of peptic ulcer disease and gastric cancer worldwide
  +
  +
=== Pathophysiology ===
  +
*Urease neutrolizes acid and induces angiogenesis
  +
*Strains with CagA, VacA, and BabA are associated with more cellular metaplasia
  +
  +
=== Epidemiology ===
  +
  +
* Present worldwide
  +
* About half of the world's population is estimated to have chronic infection[[CiteRef::zamani2018sy]]
  +
* Usually acquired during infancy or childhood
  +
* Transmission is likely fecal-oral or oral-oral
  +
  +
[[File:Prevalence of ''Helicobacter pylori'' infection across the world.jpg|thumb|Prevalence of Helicobacter pylori infection across the world. From: Zamani ''et al''. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. ''Aliment Pharmacol Ther''. 2018;47(7):868-876. doi: [https://doi.org/10.1111/apt.14561 10.1111/apt.14561].]]
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  +
== Clinical Manifestations ==
  +
  +
* Mostly asymptomatic
  +
* Complications include:
  +
** Peptic ulcer disease in 1 to 10%
  +
** Gastric cancer in 0.1 to 3%
  +
** MALT lymphoma in 0.01%
  +
  +
== Diagnosis ==
  +
  +
* Gastroscopy with biopsy for histopathology is the gold standard
  +
* Culture is challenging but necessary for phenotyping susceptibility testing
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  +
=== Urea Breath Test ===
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  +
* Patient is fed urea labelled with <sup>13</sup>C or <sup>14</sup>C isotopes, which is hydrolyzed into ammonia and isotope-labelled CO<sub>2</sub>, which is detected in exhaled breath 30 minutes later and measured by mass spectrometry (or other method)
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** The delta over baseline (DOB) (i.e. increase in labelled CO<sub>2</sub>) is compared to a threshold
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** Cutoff DOB is usually 5%
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* False negatives may be seen with PPIs (which should be held for 7 days before test), recent antibiotics (should be off of them for 4 weeks before test), bleeding ulcers (should be resolved before test), and corpus-predominant gastritis
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* False positives may be seen with [[Helicobacter heilmannii]] and rarely with other [[urease-producing organisms]] such as [[Proteus mirabilis]], [[Citrobacter freundii]], [[Klebsiella pneumoniae]], [[Enterobacter cloacae]], [[Staphylococcus aureus]], [[Staphylococcus capitis]] subsp. ''urealyticus''
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  +
=== Stool Antigen Test ===
  +
  +
* Non-invasive testing, and preferred to pediatric patients
  +
* Based on ELISA, immunochromatographic assay, and CLIA
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* Affected by PPIs (should be held for 7-14 days)[[CiteRef::manes2001ac]], antibiotics, bismuth-containing medications, and [[N-acetylcysteine]]
  +
* Sample is temperature sensitive: max 24 hours at room temperature, 72 hours at 4ºC, or long-term if frozen
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  +
=== Serology ===
  +
  +
* Includes IgM, IgA, and IgG antibodies
  +
* More false positives with IgA and IgM
  +
* Post-treatment IgG titres can take 6-12 months to fall below 50% compared to pre-treatment
  +
* Not affected by concurrent medications, unlike other non-invasive tests
  +
* Accuracy varies by strain, so ideally should use locally-validated tests
  +
  +
=== Test of Cure ===
  +
  +
* Urea breath test is preferred to stool antigen
  +
* Serology not helpful
  +
  +
==Management==
  +
  +
*Treatment is with combination therapy for 14 days followed by confirmation of eradication
  +
*First-line:
  +
**[[PBMT]] (BMT Quad): bismuth subsalicylate 524 mg p.o. four time daily, metronidazole 500 mg p.o. three to four times daily, tetracycline 500 mg p.o. four times daily for 14 days
  +
**[[PAMC]] (CLAMET Quad): PPI twice daily, [[amoxicillin]] 1 g p.o. twice daily, metronidazole 500 mg p.o. twice daily, and [[clarithromycin]] 500 mg p.o. twice daily for 14 days
  +
**[[PAC]] (PPI, [[amoxicillin]], [[clarithromycin]]), PMC (PPI, [[metronidazole]], [[clarithromycin]]), or [[PAM]] (PPI, [[amoxicillin]], [[metronidazole]]) only in areas with [[clarithromycin]] resistance <15% or with proven high local eradication rates >85%
  +
*Prior treatment failure:
  +
**[[PBMT]]: PPI twice daily, bismuth subsalicylate 524 mg p.o. four times daily, [[metronidazole]] 500 mg p.o. three to four times daily, [[tetracycline]] 500 mg p.o. four times daily
  +
**[[PAL]]: PPI twice daily, [[levofloxacin]] 500 mg p.o. once daily, and [[amoxicillin]] 750 mg p.o. three times daily for 14 days
  +
**[[PAR]]: PPI twice daily, amoxicillin 750 mg p.o. three times daily, and rifabutin 300 mg p.o. once daily for 10-14 days
  +
*Duration generally 14 days
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*Confirmation of eradication should be done 4 weeks following treatment
  +
*Recommended order of treatment, if persistently positive:
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**[[PBMT]] (or [[PAMC]])
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**[[PAMC]] (or [[PBMT]])
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**[[PAL]]
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**[[PAR]] vs. repeat endoscopy for culture and susceptibility testing
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=== Antibiotic Resistance ===
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  +
* Mechanisms:
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** [[Amoxicillin]] resistance is caused by modified PBPs (rather than [[β-lactamases]])
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** [[Clarithromycin]] resistance is caused by point mutations in the 23S rRNA of 50S ribosomal subunit
  +
** [[Metronidazole]] resistance is caused by mutations in RdxA and FrxA enzymes
  +
** [[Levofloxacin]] resistance is caused by point mutations in DNA gyrase (''gyrA'' or ''gyrB'')
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** [[Tetracycline]] resistance is uncommon and not fully understood
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** [[Rifabutin]] resistance is uncommon and caused by mutations in DNA-dependent RNA polymerase
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* The most important regional rates of resistance to pay attention to when choosing empiric treatment is to [[clarithromycin]] and [[metronidazole]], since they are most frequent
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==Further Reading==
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*''H. pylori'' Enhanced Primary Care Pathway: [[2016 version]], [https://divisionsbc.ca/sites/default/files/inline-files/HPYLORI%20Enhanced%20Primary%20Care%20Pathway%202019_0.pdf 2019 version], [https://www.specialistlink.ca/files/HPylori_PCPathway_April112020.pdf 2020 version]
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*The Toronto Consensus for the Treatment of ''Helicobacter pylori'' Infection in Adults. ''Gastroenterol''. 2016;151:51–69. doi: [https://doi.org/10.1053/j.gastro.2016.04.006 10.1053/j.gastro.2016.04.006]
  +
*Houston Consensus Conference on Testing for ''Helicobacter pylori'' Infection in the United States. ''Clin Gastroenterol Hepatol''. 2018;16(7):992-1002.e6. doi: [https://doi.org/10.1016/j.cgh.2018.03.013 10.1016/j.cgh.2018.03.013]
 
{{DISPLAYTITLE:''Helicobacter pylori''}}
 
{{DISPLAYTITLE:''Helicobacter pylori''}}
 
[[Category:Gram-negative bacilli]]
 
[[Category:Gram-negative bacilli]]

Latest revision as of 13:12, 19 September 2024

Background

  • Slow-growing Gram-negative microaerophilic bacillus with a curve, gull-wing, or spiral appearance
  • Oxidase-positive and urease-positive
  • Major cause of peptic ulcer disease and gastric cancer worldwide

Pathophysiology

  • Urease neutrolizes acid and induces angiogenesis
  • Strains with CagA, VacA, and BabA are associated with more cellular metaplasia

Epidemiology

  • Present worldwide
  • About half of the world's population is estimated to have chronic infection1
  • Usually acquired during infancy or childhood
  • Transmission is likely fecal-oral or oral-oral
Prevalence of Helicobacter pylori infection across the world. From: Zamani et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther. 2018;47(7):868-876. doi: 10.1111/apt.14561.

Clinical Manifestations

  • Mostly asymptomatic
  • Complications include:
    • Peptic ulcer disease in 1 to 10%
    • Gastric cancer in 0.1 to 3%
    • MALT lymphoma in 0.01%

Diagnosis

  • Gastroscopy with biopsy for histopathology is the gold standard
  • Culture is challenging but necessary for phenotyping susceptibility testing

Urea Breath Test

Stool Antigen Test

  • Non-invasive testing, and preferred to pediatric patients
  • Based on ELISA, immunochromatographic assay, and CLIA
  • Affected by PPIs (should be held for 7-14 days)2, antibiotics, bismuth-containing medications, and N-acetylcysteine
  • Sample is temperature sensitive: max 24 hours at room temperature, 72 hours at 4ºC, or long-term if frozen

Serology

  • Includes IgM, IgA, and IgG antibodies
  • More false positives with IgA and IgM
  • Post-treatment IgG titres can take 6-12 months to fall below 50% compared to pre-treatment
  • Not affected by concurrent medications, unlike other non-invasive tests
  • Accuracy varies by strain, so ideally should use locally-validated tests

Test of Cure

  • Urea breath test is preferred to stool antigen
  • Serology not helpful

Management

  • Treatment is with combination therapy for 14 days followed by confirmation of eradication
  • First-line:
  • Prior treatment failure:
    • PBMT: PPI twice daily, bismuth subsalicylate 524 mg p.o. four times daily, metronidazole 500 mg p.o. three to four times daily, tetracycline 500 mg p.o. four times daily
    • PAL: PPI twice daily, levofloxacin 500 mg p.o. once daily, and amoxicillin 750 mg p.o. three times daily for 14 days
    • PAR: PPI twice daily, amoxicillin 750 mg p.o. three times daily, and rifabutin 300 mg p.o. once daily for 10-14 days
  • Duration generally 14 days
  • Confirmation of eradication should be done 4 weeks following treatment
  • Recommended order of treatment, if persistently positive:

Antibiotic Resistance

  • Mechanisms:
    • Amoxicillin resistance is caused by modified PBPs (rather than β-lactamases)
    • Clarithromycin resistance is caused by point mutations in the 23S rRNA of 50S ribosomal subunit
    • Metronidazole resistance is caused by mutations in RdxA and FrxA enzymes
    • Levofloxacin resistance is caused by point mutations in DNA gyrase (gyrA or gyrB)
    • Tetracycline resistance is uncommon and not fully understood
    • Rifabutin resistance is uncommon and caused by mutations in DNA-dependent RNA polymerase
  • The most important regional rates of resistance to pay attention to when choosing empiric treatment is to clarithromycin and metronidazole, since they are most frequent

Further Reading

References

  1. ^  M. Zamani, F. Ebrahimtabar, V. Zamani, W. H. Miller, R. Alizadeh‐Navaei, J. Shokri‐Shirvani, M. H. Derakhshan. Systematic review with meta‐analysis: the worldwide prevalence of Helicobacter pylori infection. Alimentary Pharmacology & Therapeutics. 2018;47(7):868-876. doi:10.1111/apt.14561.
  2. ^  G. Manes, A. Balzano, G. Iaquinto, C. Ricci, M. M. Piccirillo, N. Giardullo, A. Todisco, M. Lioniello, D. Vaira. Accuracy of the stool antigen test in the diagnosis of Helicobacter pylori infection before treatment and in patients on omeprazole therapy. Alimentary Pharmacology & Therapeutics. 2001;15(1):73-79. doi:10.1046/j.1365-2036.2001.00907.x.