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Evaluating the effectiveness of eradication therapy first-line Helicobacter Pylori infection in children

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Monday, 24 March 2008

Diseases of the stomach and duodenum (KDP) in children - a serious medical and social problem. At present, the infection Helicobacter pylori (HP) is considered an important etiopathogenetic factor in the development of inflammatory changes in the mucosa of the gastroduodenal zone. According to several authors, HP infection of children older than 7 years with abdominal pain and / or dyspeptic syndrome is 80% (2.10). Depending on the virulent microorganism and genetic characteristics of microorganism infection outcomes H. pylori is different. Long-term persistence of the organism may lead to the development of multifocal atrophic gastritis, gastric adenocarcinoma, MALT-lymphoma.

Numerous studies have shown that the elimination of H. pylori infection in patients with gastroduodenal ulcers significantly reduces the frequency of exacerbations and complications, prevents the progression of inflammatory changes and the development of atrophy of the gastric mucosa in chronic gastritis Hp-associated (1,2,3).

Standards for the eradication of H. pylori, adopted by the Maastricht Consensus-3 in 2005, refer to the activities of pro-active response to the increase of resistance of H. pylori in relation to the previously recommended the Maastricht consensus-2 therapy protocols. According to the recommendations of the European Working Group for the Study of HP (EHPSG), possibly lengthening the course of eradication therapy to 10-14 days (6,7).

In cases where the quality "local" studies demonstrated its efficacy, may be used 7-day protocol. First-line therapy - a proton pump inhibitor (PPI) in the standard dose 2 times a day + clarithromycin 500 mg 2 times a day plus amoxicillin 1000 mg 2 times a day (or metronidazole 500 mg 2 times) is recommended if resistance is the most common strains of H.pylori to clarithromycin in the region does not exceed 10-15% and to metronidazole - 40%.

If no effect after prescribing first line assigned to second-line therapy: PPI in standard dose 2 times a day plus bismuth subsalicylate / subcitrate 120 mg 4 times daily + metronidazole 500 mg three times daily + tetracycline 500 mg 4 times daily (4 and 5).

In accordance with the provisions of the Maastricht Consensus-3, HP eradication was carried out in children with the same medications as adults, but with the calculation of doses of drugs, based on body weight. Recommendations for the diagnosis of HP infection is still similar to the agreement, except for indications that rapid urease test makes it possible to diagnose H. pylori infection and a positive result, prescribe eradication therapy without resorting to biopsy (7).

Treatment of HP infection should be affordable for the patient, well tolerated, and the number of patients cured at least 80%. The study of the effectiveness of eradication protocols conducted in our country, in adults, showed that the drug of choice in a triple first-line therapy is PPI, amoxicillin and clarithromycin (8.9).

High frequency of Helicobacter pylori infection in pediatric populations necessitates the choice of eradication schemes and duration of treatment, it is best for the children's age (10). The appointment of two antimicrobial agents within 2 weeks of their specific causes and aggressive direction with regard to microorganism. Lengthening the course of treatment up to 14 days in pediatric patients, in our opinion, is unacceptable and, of course, priority should be given more sparing schemes.

PEPTYPACK Combination drug registered in the Republic of Belarus, the relevant recommendations EHPSG - 2005 is Peptipak. In the same package, there are seven blisters each containing a set of daily drugs for eradication of line 1: omeprazole (Omepral) 20 mg в 2 times, clarithromycin (Klarikar) 500 mg в 2 times, amoxicillin (Amoksikar) 1000 mg в 2 times a day. All drugs are taken 20-30 minutes before eating. Ease of distribution of the daily dose can observe the commitment of the patient and his parents for treatment.

The aim of our study - the study of the effectiveness of the drug Peptipak as first-line protocol (PPI + clarithromycin + amoxicillin) in the eradication of H. pylori in children with duration of treatment 7 and 10 days.

We observed 47 patients (22 boys and 25 girls) aged from 10 to 17 years (mean age 13.5 years) with chronic gastritis associated with HP and duodenal ulcer disease in remission (44 pers. And 3 people ., respectively). All patients were treated at the 17th Children's Clinical clinic in Minsk. Esophagogastroduodenoscopy (EGD) was carried out based on the 2nd and 4th CST and DIKB.

Inclusion criteria: the presence of these morphological studies gastrobioptatov, the patient had received antisecretory, antibacterial and antacid drugs, free and informed consent of parents to their child's participation in the study.

Exclusion criteria from the study: primary ulcer duodenal, intolerance to antibiotics penicillin and macrolides. Diagnosis is based on history, typical complaints, physical examination data, laboratory, endoscopic and morphological studies.

Endoscopy with biopsy of the gastric mucosa (two biopsies from antrum and two - from fundal) was carried out in all patients before treatment and 40 children at 6-8 weeks after discontinuation of antibiotics or antisecretory drugs. H. pylori were detected in gastrobioptatah bacterioscopic method, and while testing - and the rapid urease method.

Separately analyzed the tolerance of the drug: estimated individual children's reactions to the organoleptic properties, recorded the presence or absence of allergy and other side effects (nausea, abdominal pain, increased frequency and changes in stool consistency).

Patients were randomized into two groups for the appointment of 7 - and 10-day patterns of H. pylori first-line therapy (Table 1). In appointing Peptipaka daily dose was calculated on the weight of the patient's body. In addition the complex treatment administered probiotic preparations for 7 days.

Table 1. Minutes of the first-line eradication therapy

Number of

No. of patients

Protocol eradication

Duration of therapy (days)

I

22

Omeprazole, amoxicillin, clarithromycin (KLA-7)

7

II

25

Omeprazole, amoxicillin, clarithromycin (OAK-10)

10

Successful eradication was stated in the absence of organisms in biopsy specimens and a negative result, rapid urease test. In analyzing the effectiveness of therapy of H. pylori was assessed clinical symptoms (general condition of the child and decrease dyspeptic pain syndromes and their intensity during the day). In each group, determined the percentage of cured rate of HP-infection among patients who received treatment in accordance with the protocol.

Family history of peptic ulcer disease and gastric cancer was diagnosed in 10 (21.3%) children. Duration of symptoms of gastric dyspepsia before the inclusion in the study ranged from 6 months. up to 3 years. On examination, patients frequently complained of pain in the epigastric region, occurring both before and after meals, early satiety, decreased appetite, nausea, belching, bloating, unstable chair. The clinical picture was dominated by a mixed option of functional dyspepsia (26 children), rarely observed diskineticheskih (17) and yazvennopodobny options (4 people). Tenderness to palpation in the epigastric and piloroduodenalnoy areas noted in almost all (97.9%) children.

At endoscopy 46 patients were identified inflammatory lesions of the mucous membrane of stomach and duodenum (edema, hyperemia, hypersecretion) of varying severity, from a child endoscopic changes were found. The defects of the mucous membrane in the form of single or multiple erosions were observed in 5 cases in 3 patients - cicatrizing ulcerative defects KDP. Related dysmotility of the upper gastrointestinal tract: the gastro-oesophageal reflux disease with esophagitis I-II degree was diagnosed in 10 children (21.3%), of which 2 cases had taken place and duodeno-gastric reflux.

Histological examination of biopsy specimens of gastric mucosa pangastrit diagnosed in 28 children (59.6%). Isolated antral lesion was observed in 38.3% of cases, the bodies of the stomach - in 1 patient. According to microscopy, colonization of mucosal HP antrum I st. detected in 10 patients (21, 3%), II art. - 16 (31, 4%) and III century. - In 21 (47.3%).

7 children who received eradication therapy, withdrew from further study due to the failure of repeated endoscopy because of a lack of complaints (3 people from the I-th group and 4 of the II-nd). According to morphological studies of biopsy specimens of gastric mucosa and the results of rapid urease test in group I eradication was achieved in 16 (84.4%), while in the II-nd group - 19 (90.4%) patients (Table 2 .)

Table 2. The results of eradication therapy

Number of

Number of patients

The effectiveness of eradication

(Absolute /%)

HP (-)

HP (+)

I

19

16 (84.4%)

3 (15.6%)

II

21

19 (90.4%)

2 (9.6%)

Pain in upper abdomen, and symptoms of dyspepsia after treatment decreased in 36 patients, regardless of the results of HP eradication. In 4 cases (failed eradication) evaluated the symptoms persisted.

These histological examination of biopsy specimens of gastric mucosa before and after eradication therapy are shown in Table 3.

Table 3. Histologic indicators of activity and the severity of inflammation in the gastric mucosa before and after eradication

The histological

Indicators

Gastric mucosa

Department of fundic

before treatment (n = 47) /

after treatment (n = 40)

antral

before treatment (n = 47) /

after treatment (n = 40)

abs.

%

abs.

%

Activity of inflammation

-

18/26

38,3 / 65

11/22

23,4 / 55

+

19/11

40,5 / 27,5

13/14

27,6 / 35

+ +

9 / 3

19,1 / 7,5

20 / 4

42,6 / 10

+ + +

1 / -

2,1 / -

3 / -

6.4 / -

The intensity of inflammation

-

18/23

38,3 / 57,5

1 / 19

2,1 / 47,5

+

15/13

31,9 / 32,5

4 / 17

8,5 / 42,5

+ +

10 / 4

21,3 / 10

23 / 3

48,9 / 7,5

+ + +

4 / -

8.5 / -

19 / 1

40,5 / 2,5

HP infection after eradication in a month in most patients disappeared neutrophil and mononuclear infiltration of the epithelium and lamina propria mucosa, and significantly decreased activity and intensity of inflammation of the gastric mucosa.

Side effects leading to discontinuation of treatment were observed. In children we observed no cases of skin rash or other allergic reactions to the drug. Three patients reported an increase in stool frequency to 4 times a day for 2 days, two indicated nausea, one - on a metallic taste in your mouth. The number of side effects was similar in both groups.

Thus, the study showed that triple 10-day first-line therapy (omeprazole, clarithromycin and amoxicillin) is an efficient and optimal for the eradication of Helicobacter pylori in children. The scheme can be applied successfully in an outpatient setting.

Minutes of first-line therapy, including omeprazole, clarithromycin, and amoxicillin (Peptipak) in children with chronic HP-associated gastritis provide a high level of eradication. The effectiveness of eradication increases with increasing duration of treatment up to 10 days (p <0.05). Peptipak well tolerated, clinically significant adverse reactions in study groups of children were observed. After the destruction of H. pylori infection is significantly reduced inflammation of the gastric mucosa.

The use of triple first-line therapy (omeprazole, clarithromycin, amoxicillin) leads to rapid clinical improvement.

References:

1. Aruin LI The quality of healing of gastroduodenal ulcers: functional morphology, the role of methods of pathogenetic therapy / / Experimental and clinical gastroenterology. Reprint. 2006. 5s.

2. Bovbel IE Comparative analysis of clinical and morphological changes and lipid metabolism, the level of srednemolekulyarnyh peptides in children with chronic gastroduodenitis. Abstract. diss., PhD. honey. of Sciences. Minsk, 1999 .- 22s.

3. Diseases of the esophagus and stomach. Ivashkin VT Sheptulin AA In brief. A Practical Guide. - M.: MEDpress-Inform, 2002. - 144s.

4. Isakov, VA Kislotozavisimyh disease therapy with proton pump inhibitors in the Q & A / / Gastroenterology / Surgery. Reprint.2006, 7c.

5. Lapina TL Macrolide antibiotic clarithromycin in the eradication therapy of infections Helicobacter pylori / / of breast cancer. The application. Diseases of the digestive organs. Volume 8, № 1, 2006. P.39-42.

6. Loginov, AF "Maastricht-3" - the modern tactics of diagnosis and treatment of infection Helicobacter pylori / / Farmateka. № 12 (127) 2006. - S. 46-48.

7. Maev IV, Samsonov AA Current standards of treatment kislotozavisimyh diseases associated with H. pylori (Maastricht Consensus materials 3) / / Gastroenterology. Supplement to Consilicum medicum № 1, 2006.S.3-8

8. Pimanov SI, Makarenko EV Analysis of the effectiveness of eradication protocols infection Helicobacter pylori / / recipe. - 2005. - № 1. - S. 19-23.

9. Pimanov SI, Makarenko EV, YI Queen Possibility of empirical eradication therapy in patients with duodenal ulcer in the Republic of Belarus / / recipe. - 2006. - № 1 (45). - S. 56-60.

10. Khavkin AI, NS Zhikharev Current principles of therapy of H. pylori in

11. children / / Russian Journal of Medicine. Volume 13, № 3, 2005. P.137-139.

IE Bovbel, VY Malyugin
Medical News № 2, 2008

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