Helicobacter pylori are one of the most common disease-causing pathogens in humans. According to some estimations, about 50 percent of the human population is infected with helicobacter pylori. There are differences in its prevalence geographically as it is more prevalent in developing countries than in the developed world. It is a gram-negative, spiral-shaped, and flagellated bacterium and due to its morphological characteristics, it can colonize and cause diseases in the stomach and duodenum.
Helicobacter pylori are involved in causing inflammation in the stomach and various diseases related to it. H.pylori causes stomach ulcers, stomach cancer, metaplasia and mucosa-associated lymphoid tissue (MALT), and other conditions like iron deficiency, vitamin B12 deficiency, and idiopathic thrombocytopenia. The WHO has categorized H.pylori as a group 1 carcinogen, and H.pylori associated stomach cancer constitutes 5 percent of all cancers globally. The WHO has also categorized it as a high-priority organism for which there is a need for research towards developing newer drugs considering the decreasing effectiveness of currently available drugs.
The effectiveness of current treatment options for Helicobacter pylori has been decreasing in recent years due to the challenge of antibiotic resistance. The failure rate of current treatment regimens is 25 percent to 40 percent as the bacterial resistance to clarithromycin and metronidazole has been growing steadily. Hence, antibiotic resistance affects the effectiveness of current eradication treatments negatively and this has presented a significant challenge for the eradication of this organism and also directed the research towards the development of different combinations of many drugs and discovering novel and more effective treatment options.
Following are the recommended and suggested treatment regimens. They are indicated depending on the presence of antibiotic resistance against one or a group of drugs and the availability of susceptibility testing.
Clarithromycin triple therapy
This is the standard treatment option against H.pylori. It is the combination of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin. Metronidazole can be used in place of amoxicillin too. It is given for 14 days. In recent years, antibiotic resistance against clarithromycin has been well documented and it is recommended to avoid clarithromycin in areas where the resistance of h.pylori against it has been documented. Over 15 percent or the patients have had previous exposure to macrolides.
Bismuth quadruple therapy
This regimen consists of a proton pump inhibitor, tetracycline, nitroimidazole, and bismuth. It is given for 10 to 14 days. It is strongly recommended as a first-line treatment option in patients who have a history of previous exposure to a macrolide or in which clarithromycin resistance is high. It can also be a good treatment option for patients who are allergic to penicillin. Metronidazole resistance may render this treatment regimen slightly less effective but this resistance does not have as much of an impact as in clarithromycin triple therapy.
This combination treatment consists of a proton pump inhibitor, amoxicillin, clarithromycin, and nitroimidazole. It is given for 10 to 14 days. This treatment regimen is as effective as clarithromycin triple therapy and it has a similar tolerability profile.
In this treatment regimen, amoxicillin and a proton pump inhibitor (PPI) are given initially for five to seven days and after that, the patient is given nitroimidazole, clarithromycin, and a proton pump inhibitor for five to seven days. This treatment regimen has been shown to improve eradication rates when it is extended to 14 days. There is ongoing research in this area and further studies may prove or refute its effectiveness against H.pylori infection.
In this treatment regimen, a proton pump inhibitor and amoxicillin are given seven days and after that, clarithromycin, amoxicillin, and nitroimidazole are given for seven days. This treatment option has been shown to be as effective as clarithromycin triple therapy. One disadvantage relating to this option can be its limited use due to its complexity.
Levofloxacin triple therapy
It is a combination of amoxicillin, a proton pump inhibitor, and levofloxacin. It is given for 10 to 14 days. Levofloxacin is an antibiotic that has a wide range of antimicrobial activity against gram-positive and gram-negative bacteria including H.pylori. There is a dearth of data available on the efficacy of this treatment regimen but its effectiveness is comparable to clarithromycin triple therapy. This treatment regimen can be given as a first-line treatment option. The best options containing a fluoroquinolone are fluoroquinolone containing sequential therapy (a proton pump inhibitor and amoxicillin for five to seven days, and after that, a proton pump inhibitor, a fluoroquinoline, and a nitroimidazole for five to seven days) and LOAD therapy (levofloxacin, nitazoxanide, doxycycline, and omeprazole for seven to 10 days).
Rifabutin triple therapy
This treatment regimen contains omeprazole magnesium, amoxicillin, and rifabutin. These drugs are given for 14 days every 8 hours. It was approved by FDA in 2019 and it has shown greater efficacy against H.pylori than the comparative group in a study.
Newer treatment options
In recent years, there has been ongoing research on developing many newer agents to overcome bacterial resistance to traditional drugs. Some of these agents are mentioned below:
- Cathelicidins and defensins are human antimicrobial peptides (AMPs) and it has been shown that they limit H.pylori growth in mice.
- Oligo-acyl-lysyl peptides are similar to AMPs structurally and functionally and their antibacterial effect and anti h.pylori effect have been documented.
- SQ109 is another compound that has shown anti-H. pylori activity and has been shown to be safe in many trials.
- Phytotherapy is another treatment option that has been explored in research. Many compounds have shown promising anti-H.pylori effect.
- Micro and nano-technology is another area that has been researched to study its promise in treating and eradicating H.pylori infection.
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National center for biotechnology information, Recent progress in H.pylori treatment, Accessed June 22, 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004604
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