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One of the most debated problems is who should be treated for H. pylori infection. In adults, the most recent indications for H. pylori treatment are listed in the Table 6.7, derived from the Maastricht 2-2000 Consensus Report.100

Each of the three Pediatric Consensus Reports (North American, European and Canadian) outlined recommendations for the detection of H. pylori infection.96-98 Regarding the H. pylori-positive subjects to be treated, the NASPGHAN supports the treatment only in case of PUD and MALToma.96 The European Pediatric Task Force on Helicobacter pylori (EPTFHP) consensus statement suggests providing treatment for the infection if H. pylori is identified in a child at endoscopy (Table 6.6).97

Children with H. pylori-positive PUD must be submitted to eradicating treatment, because

Table 6.6 Guidelines for the management of Helicobacter pylori infection in children

Diagnosis Evidence Treatment


North American Society of Pediatric Gastroenterology, Hepatology and Nutrition

Endoscopy and histology II peptic ulcer disease


13C-urea breath test II MALToma


atrophic gastritis

I. metaplasia


triple therapy for 1-2 weeks

European Pediatric Task Force on Helicobacter pylori

Endoscopy and histology peptic ulcer disease

13C-urea breath test for follow-up all Helicobacter pylori-positive children after

endoscopy (information of the possibility

of symptoms' persistence)

Table 6.7 The Maastricht 2-2000 guidelines for the treatment of Helicobacter pylori infection in adults

Strongly recommended indications

Peptic ulcer disease


Atrophic gastritis

Post-gastric cancer resection

First-degree relatives of gastric cancer patients

Patient's wishes (after physician consultation)

Advisable indications

Functional dyspepsia (subset of patients)

Gastroesophageal reflux disease (in patients requiring long-term proton pump inhibitor therapy) Users of non-steroidal anti-inflammatory drugs relapse after effective ulcer healing has been demonstrated in 47-80% of children with persistent H. pylori infection, and exceptionally in those in whom H. pylori has been eradicated.31,37,97 Symptomatic relief of dyspeptic symptoms is usually achieved.73

H. pylori eradication in children with chronic active gastritis is associated with evident histological improvement,69 but remission of symptoms does not necessarily follow.73,97 However, if the infection is not treated, worsening of gastritis and of the clinical picture, particularly in males and in children infected with Cag-A-positive strains, has been documented in a close follow-up study.101 In adults as well as in teenagers with iron-deficient anemia, H. pylori eradication was associated with a rise in hemoglobin levels and in ferritin values, suggesting that treatment should be considered.82-85

In adults with peptic esophagitis, the treatment of associated H. pylori infection is a question of debate.102 Some authors have suggested that esophagitis and gastroesophageal reflux disease (GERD) may be exacerbated by eliminating the protecting buffering effect of H. pylori infection.103 Nevertheless, a causal relationship between these phenomena remains unproven, and is mainly based on retrospective analyses or epidemiological hypothesis. The small number of prospective trials in adults has not consistently demonstrated an increased risk of GERD after H. pylori eradica-tion.104

In a study planned to answer the question of whether eradication of H. pylori infection in children with RAP should result in clinical improvement, no correlation was seen between eradication and disappearance of RAP, after 3 or after 6 months of observation.105

To date, extrapolation of data from randomized controlled trials in adults has been the basic approach to treating children with H. pylori infection. A systematic review of the small published open trials in 870 children from 1987 to 2000 has recently been published.106 A total of 79 children were treated with one drug (monotherapy); 345 were treated with dual therapy, including two antibiotics or one antibiotic plus bismuth compounds or H2-receptor antagonists (H2RA) or proton pump inhibitors (PPIs); and 446 with a bismuth- or PPI-based triple therapy plus two antibiotics. In pediatrics, the most frequently utilized antibiotics were amoxicillin, clar-

ithromycin, and the nitroimidazoles, metronida-zole or tinidazole. The reasons for the development of combined therapies were:

  • 1) Different strains with different antibiotic sensitivity may colonize the same patient. Sensitivity to amoxicillin, clarithromycin and nitroimidazoles is one of the key factors in the eradication rates. Unpublished data collected by the EPTFHP showed metronida-zole, clarithromycin or double resistance before the first therapy in 24.5%, 20% and 7%, respectively, of 400 H. pylori-infected children aged under 15 years.
  • 2) Stability and efficacy of antibiotics are often impaired in the acid environment. This consideration prompted the combination of antibiotics with drugs able to increase the gastric pH (H2RA or PPI).

In general, monotherapy with one antibiotic, or bismuth compounds, or H2RA or PPI showed a very low eradication rate and it is not recommended. Combination of one antibiotic with PPI was not satisfactory (mean eradication rate of 39%), while combination of amoxicillin with nitroimidazole or one of the two antibiotics with bismuth salts was tried in 248 children, with a mean eradication rate of 73-76%.106

Triple therapy schedules did not work much better. A recent randomized clinical trial confirmed that 1 week of omeprazole-amoxicillin-clarithromycin resulted in successful eradication of H. pylori in 75% of 73 children <15 years old.107 A higher efficacy was obtained with the combination of bismuth, metronidazole and clar-ithromycin, with an eradication rate of 95.5% in 22 children.108 Data from two abstracts with a total of 58 children treated with omeprazole-amoxi-cillin-tinidazole schedules for 1 or 2 weeks showed 86% and 100% eradication rates, respec-


Concerning the duration of the different regimens, dual therapies with amoxicillin and nitroimida-zole, or one of these two antibiotics and bismuth, reached better eradication rates (84% vs. 74%) when administered for 2 weeks rather than 1 week. In contrast, PPI-based triple therapies gave similar results when given for 1 or 2 weeks (75% vs. 77%).106 Thus, it would appear that 1 week of PPI-based triple therapy with amoxicillin and clar-ithromycin or a nitroimidazole should be the first choice of treatment. If available, sensitivity data may help in making the final decision (Table 6.8).

Monitoring of the treatment should be based on non-invasive tests, and, among these, 13C-UBT is

Table 6.8 Protocols of Helicobacter pylori treatment in children

First-line therapy

PPI (1 mg/kg per day up to 20 mg bid) plus Amoxicillin (50 mg/kg per day bid up to 1 g bid) plus Clarithromycin (15 mg/kg per day up to 500 mg bid) or Metro(ti)nidazole (20 mg/kg per day up to 500 mg bid) for 1 week

In case of failure to eradicate the bacterium: Second-line therapy

Amoxicillin + clarithromycin or metronidazole (based on antibiotic testing or, in the absence of testing, that not used in the first line) plus

PPI or bismuth salts (480 mg/1.73 m2 of body surface up to 480 qid) for 2 weeks Successive failures and retreatment need antibiotic testing and case-to-case evaluation PPI, proton pump inhibitor; bid, twice a day; qid, four times a day the most recommended.97 Recent data showed that fecal H. pylori antigen assays could be an effective alternative.109 Re-infection after eradication is uncommon in children, and treatment of the affected family member at present is not supported.17

In the case of relapse, biopsy culture for antibiotic sensitivity testing should be proposed for a better chance of eradication. If culture is not available or if H. pylori does not grow, substitution of clar-ithromycin with a nitroimidazole (and vice versa) is the first step, because of the high probability of development of a resistance to either drug. A 2-week regimen should be offered to relapsing patients (Table 6.8).

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