Treatment of Helicobacter pylori infection in children: A systematic review

Table 5 Synthesis of results from included studies

Ref.	Adverse events	Deaths	Eradication rates	Conclusion
Moubri et al[22]	Mild and moderate symptoms, mainly gastrointestinal.	No	(1) ITT: Group A - Amoxicillin - based triple therapy: 68%; Group B - Metronidazole - based triple therapy: 80%; and (2) PP: Group A - Amoxicillin - based triple therapy: 71%; Group B - Metronidazole - based triple therapy: 88%.	The group B eradication rates were higher than Group A rates. The differences were only significant for PP (P < 0.03).
Namkin et al[23]	Loss of appetite.	No	Probiotic group: 0.40 ± 0.32 to 0.21 ± 0.27 average HpSA title; P = 0.005. Placebo group: 0.24 ± 0.2 to 0.24 ± 0.27 average HpSA title; P = 0.89.	There was no significant difference between the two groups in relation to the eradication rate of H. pylori infection (P = 0.16), however the decrease in the concentration of HpSA was significantly greater in the group treated with probiotics (P = 0.005 vs P = 0.89).
Akcam et al[24]	Abdominal pain, nausea, vomiting, constipation, belching, changes in taste, poor appetite and diarrhea.	No	Standard triple therapy group: 68.9%; Standard triple therapy group + probiotics: 66.6%; P = 0.78.	There was no statistically significant difference between the two groups.
Tolone et al[25]	Epigastric pain, nausea, vomiting, diarrhea and constipation.	No	Group A standard therapy group: 76.4%; Group B standard therapy + probiotics: 88.2%; P = 0.1.	There was no significant difference in the rate of H. pylori eradication between group A and group B, however, the side effects were significantly greater (P < 0.05) in group A than in group B.
Farahmand et al[26]	Vomiting, abdominal pain, iron deficiency, anemia and gastrointestinal bleeding.	No	Group A - Ciprofloxacin-based triple therapy: 87.9%; Group B - Furazolidone-based triple therapy: 60.6%; P = 0.011.	This study concludes that triple therapy consisting of ciprofloxacin, amoxicillin and omeprazole is highly valuable as H. pylori is not resistant to the antimicrobials.
Ahmad et al[27]	Diarrhea, nausea, vomiting and abdominal swelling.	No	Group A - Triple therapy + placebo: 69.69%; Group B - Triple therapy + probiotics: 90.09%; P = 0.04.	The group treated with the combination of probiotic and standard therapeutic regimen showed a more significant eradication rate. Supplementation with probiotics has a positive effect on H. pylori and decreases adverse events and effectiveness.
Bin et al[28]	Diarrhea.	11	Group A - Triple therapy + S. boulardii: 71.4%; Group B - Only triple therapy: 61.9%; P = 0.51	The probiotic prevented diarrhea associated with triple H. pylori eradication therapy. In addition, when diarrhea developed, it was less severe and of shorter duration in the S. boulardii group. The probiotic increased the adherence to H. pylori eradication therapy, which may be related to a small increase in H. pylori eradication by 10 percent.
Kasiri et al[29]	Intolerance to clarithromycin.	No	Group A - Amoxicillin-based triple therapy: 87.2%; Group B - Metronidazole-based triple therapy: 92.5%; P = 0.43.	There was no significant difference in the complete recovery and eradication of H. pylori between the two regimens. Both therapeutic regimens were considered to be effective, since both have similar rates of eradication, recovery and side effects.
Iwańczak et al[30]	-	-	Group I - Amoxicillin-based triple therapy: 78.2%; Group II Metronidazole-based triple therapy: 78.2%; Group III - Sequential therapy: 91.3%; P > 0.5.	For strains susceptible to clarithromycin: treatment with amoxicillin-based triple therapy was the most effective. For regions with clarithromycin resistance greater than 20%, quadruple therapy or therapy based on the susceptibility of the strains is recommended.
Tümgör et al[31]	Nausea, headache, vomiting, abdominal pain and diarrhea.	-	Group A - Clarithromycin-based triple therapy: 46.6%; Group B - Clarithromycin-based triple therapy + vitamin E: 64.4%; P = 0.13.	Although, Group B showed a higher rate of eradication, no statistically significant difference was observed between the two groups.
Ali Habib et al[32]	-	No	Group A - Standard therapy: 55.6%; Group B - Sequential therapy: 57.1%; P = 0.949.	The rates of H. pylori eradication were not significantly different in sequential vs standard therapy. In addition, serum ferritin was not significantly different between the two therapies and in the same therapy group before and after treatment.
Ustundag et al[33]	Abdominal pain and nausea.	No	ITT: Group A - Standard triple therapy: 58.8%; Group B - Standard triple therapy + symbiotic: 77.1%; P = 0.16. PP: Group A: 64.5%; Group B: 81.8%; P = 0.19.	The results of the study demonstrated that the addition of Bifidobacterium lactis B94 (5 × 109 CFU/dose) plus inulin once daily to standard triple therapy did not show superiority in eradication rates compared to standard triple therapy administered alone.
Huang et al[34]	Nausea, vomiting and diarrhea.	-	(1) ITT: Group A – 10-d sequential therapy: 81.4%; Group B – 7 d triple standard therapy: 61.9%; Group C – 10 d triple standard therapy: 67.7%; P < 0.05; and (2) PP: Group A – 10 d sequential therapy: 89.7%; Group B – 7 d triple standard therapy: 70.8%; Group C – 10 d triple standard therapy: 77.8%; P < 0.05.	The 10 d sequential regimen was significantly more effective than the 7 or 10 d triple regimens in eradicating Chinese children. In addition, the adverse events between the three groups were also similar, with no statistical differences P > 0.05.
N Şirvan et al[35]	Abdominal pain, nausea and diarrhea.	-	Group 1 - Standard triple therapy + symbiotic: 88%; Group 2 - Standard triple therapy: 72%; P = 0.046.	The rate of eradication was statistically higher in group I. The addition of probiotics to triple therapy is effective in eradicating H. pylori infection in children and is generally useful in reducing or eliminating dyspeptic symptoms, such as abdominal pain, diarrhea and vomiting.
Baysoy et al[36]	Metallic taste sensation, abdominal pain, diarrhea, vomiting, rash, itching.	-	(1) ITT: Group A- Standard triple therapy: 46.0%; Group B - Sequential therapy group: 40.9%; and (2) PP: Group A - Standard triple therapy: 54.2%; Group B - Sequential therapy group: 48.6%.	Sequential ornidazole therapy did not show superiority compared to standard triple treatment in children with H. pylori infection.
Esmaeili-Dooki et al[37]	-	-	(1) ITT: Group 1 - Clarithromycin-based triple therapy: 62.5%; Group 2 - Amoxicillin-based triple therapy: 56.2%; P = 0.4; and (2) PP: Group 1 - Clarithromycin-based triple therapy: 69%; Group 1 - Amoxicillin-based triple therapy: 61.9%; P = 0.431.	The therapeutic response was observed in more than half of the patients treated with triple therapy of the H. Pylori eradication regimen, including azithromycin or clarithromycin, and there was no significant difference between the two treatment groups.
Laving et al[38]	-	-	Conventional therapy Group: 48.8%; 10 d sequential therapy Group: 84.6%; P = 0.02.	The sequential treatment had a significantly higher rate of H. pylori eradication than conventional treatment.
Prieto-Jimenez et al[39]	Abdominal pain, nausea, diarrhea, rash.	No	(1) ITT: Group I - Quadruple sequential eradication and placebo: 44.8%; Group II - Quadruple sequential eradication and iron: 43.7%; Group III: Iron and placebo: 17.4%; Group IV: Placebo alone: 7.7%; P < 0.001; and (2) PP: Group I - Quadruple sequential eradication and placebo: 56.5%; Group II - Quadruple sequential eradication and iron: 50%; Group III: Iron and placebo: 20%; Group IV: Placebo alone: 10.5%; P < 0.001.	A sequential quadruple regimen eradicated H. pylori in only half of asymptomatic children who received this treatment. Eradication rates did not differ between patients who received iron supplementation and those who received placebo.
Nguyen et al[40]	No reported.	No	(1) Group A: Antibiotic sensitive - 79% using high medication dosages, P = 0.278; 75% using lansoprazole twice daily, P = 0.096. Antibiotic resistant - 67.5% using high medication dosages, P = 0.006; 69.2% using lansoprazole twice daily, P = 0.004; and (2) Group B: Antibiotic sensitive - 85.2% using high medication dosages, P = 0.278; 87.5% using lansoprazole Twice daily, P = 0.096. Antibiotic resistant - 45.3% using high medication dosages, P = 0.096; 50.0% using lansoprazole Twice daily, P = 0.004.	The prevalence of resistance to clarithromycin, metronidazole, and amoxicillin was 50.9%, 65.3% and 0.5%, respectively. The two treatment regimens used did not successfully eradicate H. pylori in Vietnamese children, mainly because of the unexpectedly high prevalence of antibiotic resistance.
Bontems et al[41]	Abdominal pain, diarrhea, nausea and vomiting.		(1) ITT: Group A – 10 d sequential treatment: 81.9%; Group B: 7 d triple therapy: 71.9%; and (2) PP: Group B – 10 d sequential treatment: 88.3%, Group B: 7 d triple therapy: 80.8%.	The sequential treatment is greatly effective for eradicating H. pylori in children except in clarithromycin-resistant strains. Sequential treatment can be used as a first-line therapy, but only in areas with a low clarithromycin resistance rate.

ITT: Intention-to-treat; PP: Per protocol; H. pylori: Helicobacter pylori.