Effectiveness and Tolerance of Treatments for H pylori
Effectiveness and Tolerance of Treatments for H pylori
Objective. To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens.
Design. Systematic review and network meta-analysis.
Data Sources. Cochrane Library, PubMed, and Embase without language or date restrictions.
Study Selection. Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults.
Results. Of the 15,565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported.
Conclusion. Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.
Although Helicobacter pylori is thought to have infected humans for more than 58,000 years, it was first isolated in 1982. It is a Gram negative bacterium found on the luminal surface of the gastric epithelium.H pylori is a potentially curable cause of a diverse spectrum of diseases such as dyspepsia, peptic ulcer disease, gastric mucosa associated lymphoid tissue lymphoma, and gastric cancer. Surprisingly, a series of extra-gastric and even extra-digestive diseases, including haematological disorders such as idiopathic thrombocytopenic purpura and iron deficiency anaemia, cardiovascular diseases, as well as neurological disorders are associated with H pylori. On a global scale, H pylori is the most infectious human pathogen, affecting about 50% of the population. In northern Europe and North America, only one third of adults have this bacterium, whereas in southern and eastern Europe, South America, and Asia, more than 50% of people are estimated to be infected.H pylori occurs commonly in developing countries, whereas the infection rates are decreasing in developed countries, potentially indicating that socioeconomic status and living standards might play roles in the distribution of the infection. Initially, antibiotic treatment was popular and effective. In the early 21st century, European guidelines on the management of H pylori infection recommended a "standard triple treatment" composed of a proton pump inhibitor plus clarithromycin, together with amoxicillin or metronidazole. Ranitidine bismuth citrate based triple treatment, including ranitidine bismuth citrate together with any two of amoxicillin, clarithromycin, and metronidazole has proved to have similar efficacy as the standard triple treatment. However, in less than a decade the effectiveness of the most commonly recommended treatments declined to unacceptably low levels, mainly as a result of the development of resistance to antibiotics.
Treatment regimens have been evolving to find the most effective approaches. Some researchers showed a sequential treatment consisting of five days of a proton pump inhibitor plus amoxicillin followed by five additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin to be an alternative approach. A bismuth based quadruple treatment including bismuth, a proton pump inhibitor, and two antibiotics was also accepted as an alternative first line treatment in many studies. Concomitant treatment with a proton pump inhibitor and three different antibiotics also showed acceptable efficacy in some circumstances. In this regimen, all drugs are given concomitantly and not in sequence. Some researchers believe that the principal advantage of this regimen is the worldwide availability of antibiotics, compared with bismuth compounds. In addition, the antibiotic selection or duration of treatment of this regimen is not standardised. Additionally, levofloxacin is an effective alternative to current standard antibiotics and tackles the primary resistance to macrolides and nitroimidazoles. Therefore several studies also recommended a levofloxacin based triple treatment, containing a proton pump inhibitor, levofloxacin, and one antibiotic. Previous studies reported that adding probiotics improved the effectiveness of H pylori eradication during standard triple treatment in some circumstances. Therefore a probiotic supplemented triple treatment has also been considered as a treatment option. A novel hybrid treatment consisting of a dual treatment with a proton pump inhibitor and amoxicillin for seven days, followed by a concomitant quadruple treatment with a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days produces high eradication rates and represents a promising first line treatment option. The standard triple treatment, ranitidine bismuth citrate based triple treatment, bismuth based quadruple treatment, concomitant treatment, levofloxacin based triple treatment, and probiotic supplemented triple treatment can be used for seven days and can be extended to 10 or 14 days. The sequential treatment is generally used for 10 days and can be extended to 14 days. The hybrid treatment is commonly used for 14 days. According to previous meta-analyses, extending treatment delivery could enhance treatment effects in some circumstances.
Treatment of this widespread infection remains an ongoing challenge, given the estimated rates of infection in populations and the growing resistance of bacteria to antibiotics. Many treatment approaches have been developed, but it is unknown which eradication treatments are more effective and also tolerable. Previous meta-analyses of H pylori eradication treatments used conventional methods rather than network meta-analyses. In the conventional approach, only direct comparisons between treatments are possible where these have been reported in studies. This limits any conclusion about the relative efficacy and tolerance of treatments that have not been directly compared in existing studies. Network meta-analyses permit both direct and indirect comparisons across treatments, provided that a common comparator exists. We conducted a systematic review and network meta-analysis to compare the efficacy and tolerance among different treatments for the eradication of H pylori infection.
Abstract and Introduction
Abstract
Objective. To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens.
Design. Systematic review and network meta-analysis.
Data Sources. Cochrane Library, PubMed, and Embase without language or date restrictions.
Study Selection. Full text reports of randomised controlled trials that compared different eradication treatments for H pylori among adults.
Results. Of the 15,565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported.
Conclusion. Comparison of different eradication treatments for H pylori showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of H pylori.
Introduction
Although Helicobacter pylori is thought to have infected humans for more than 58,000 years, it was first isolated in 1982. It is a Gram negative bacterium found on the luminal surface of the gastric epithelium.H pylori is a potentially curable cause of a diverse spectrum of diseases such as dyspepsia, peptic ulcer disease, gastric mucosa associated lymphoid tissue lymphoma, and gastric cancer. Surprisingly, a series of extra-gastric and even extra-digestive diseases, including haematological disorders such as idiopathic thrombocytopenic purpura and iron deficiency anaemia, cardiovascular diseases, as well as neurological disorders are associated with H pylori. On a global scale, H pylori is the most infectious human pathogen, affecting about 50% of the population. In northern Europe and North America, only one third of adults have this bacterium, whereas in southern and eastern Europe, South America, and Asia, more than 50% of people are estimated to be infected.H pylori occurs commonly in developing countries, whereas the infection rates are decreasing in developed countries, potentially indicating that socioeconomic status and living standards might play roles in the distribution of the infection. Initially, antibiotic treatment was popular and effective. In the early 21st century, European guidelines on the management of H pylori infection recommended a "standard triple treatment" composed of a proton pump inhibitor plus clarithromycin, together with amoxicillin or metronidazole. Ranitidine bismuth citrate based triple treatment, including ranitidine bismuth citrate together with any two of amoxicillin, clarithromycin, and metronidazole has proved to have similar efficacy as the standard triple treatment. However, in less than a decade the effectiveness of the most commonly recommended treatments declined to unacceptably low levels, mainly as a result of the development of resistance to antibiotics.
Treatment regimens have been evolving to find the most effective approaches. Some researchers showed a sequential treatment consisting of five days of a proton pump inhibitor plus amoxicillin followed by five additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin to be an alternative approach. A bismuth based quadruple treatment including bismuth, a proton pump inhibitor, and two antibiotics was also accepted as an alternative first line treatment in many studies. Concomitant treatment with a proton pump inhibitor and three different antibiotics also showed acceptable efficacy in some circumstances. In this regimen, all drugs are given concomitantly and not in sequence. Some researchers believe that the principal advantage of this regimen is the worldwide availability of antibiotics, compared with bismuth compounds. In addition, the antibiotic selection or duration of treatment of this regimen is not standardised. Additionally, levofloxacin is an effective alternative to current standard antibiotics and tackles the primary resistance to macrolides and nitroimidazoles. Therefore several studies also recommended a levofloxacin based triple treatment, containing a proton pump inhibitor, levofloxacin, and one antibiotic. Previous studies reported that adding probiotics improved the effectiveness of H pylori eradication during standard triple treatment in some circumstances. Therefore a probiotic supplemented triple treatment has also been considered as a treatment option. A novel hybrid treatment consisting of a dual treatment with a proton pump inhibitor and amoxicillin for seven days, followed by a concomitant quadruple treatment with a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days produces high eradication rates and represents a promising first line treatment option. The standard triple treatment, ranitidine bismuth citrate based triple treatment, bismuth based quadruple treatment, concomitant treatment, levofloxacin based triple treatment, and probiotic supplemented triple treatment can be used for seven days and can be extended to 10 or 14 days. The sequential treatment is generally used for 10 days and can be extended to 14 days. The hybrid treatment is commonly used for 14 days. According to previous meta-analyses, extending treatment delivery could enhance treatment effects in some circumstances.
Treatment of this widespread infection remains an ongoing challenge, given the estimated rates of infection in populations and the growing resistance of bacteria to antibiotics. Many treatment approaches have been developed, but it is unknown which eradication treatments are more effective and also tolerable. Previous meta-analyses of H pylori eradication treatments used conventional methods rather than network meta-analyses. In the conventional approach, only direct comparisons between treatments are possible where these have been reported in studies. This limits any conclusion about the relative efficacy and tolerance of treatments that have not been directly compared in existing studies. Network meta-analyses permit both direct and indirect comparisons across treatments, provided that a common comparator exists. We conducted a systematic review and network meta-analysis to compare the efficacy and tolerance among different treatments for the eradication of H pylori infection.