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The effectiveness of the eradication of Helicobacter pylori infection in children first-line drugs

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Thursday, 29 May 2008

In practice, gastroenterology diseases of stomach and duodenal ulcers in children are the most common. Significant role in the development of inflammatory changes in mucosal infection belongs Helicobacter pylori (HP).

Infection with Hp occurs mainly in childhood, and without proper treatment is a lifelong persistence of bacteria. According to several authors HP infection of children older than 7 years with abdominal pain and / or dyspeptic syndrome is 80%.

Depending on the virulent microorganism and genetic characteristics of microorganism infection outcomes H. pylori may be different. Long-term persistence of the organism may lead to the development of multifocal atrophic gastritis, gastric adenocarcinoma, MALT-lymphoma. In recent years there has been a tendency to an increase in severe changes in the stomach, leading to the development of serious complications that worsen the overall condition of the child and requires prolonged and expensive treatment.

Standards for the eradication of infection Helicobacter pylori, taken 3rd Maastricht Consensus in 2005. Belong to the pre-emptive actions needed to respond to the growth of H. pylori resistance to recommended earlier schemes. According to current regulations, a 14-day duration of treatment is more effective in comparison with the 7-day. In cases where the quality "local" studies demonstrated its efficacy, may be used 7-day protocol, which includes a proton pump inhibitor (PPI) in the standard dose of 2 times per day + clarithromycin 500 mg 2 times a day plus amoxicillin 1000 mg 2 times per day (or metronidazole 500 mg 2 times). In accordance with current regulations, the treatment of HP infection should be affordable for the patient, well tolerated, the number of patients cured at least 80%.

PEPTYPACK Combination drug registered in the Republic of Belarus, the relevant recommendations EHPSG - 2005 is Peptipak (Peptirac). 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.

First-line therapy is recommended if the resistance is the most common strains of H.pylori to clarithromycin in the region does not exceed 10-15% and to metronidazole - 40%. In the first-line therapy Maastricht-3 suggests the possibility of replacing amoxicillin for metronidazole (500 mg в 2 times), if the most common strains resistant to metronidazole HP does not exceed 40%. In our region, the frequency of antibiotic resistance in strains of HP to metronidazole varies from 40% to 55.5%, so the use of triple eradication protocols including this drug is not sufficiently effective.

Recently, to improve the effectiveness of eradication therapy proposed scheme, including bismuth tripotassium ditsitrat. Kvadroterapiya using bismuth drugs is a possible alternative to the protocol as a "first choice". The latter provision is new in terms of normative statements, though, and used in practice earlier.

According to the recommendations of the "Maastricht-W", eradication of HP in children should be conducted with the same medications as adults, with the calculation of the daily doses of drugs, based on body weight. Conducted in our country studies in adults have shown that the choice of protocol eradication therapy is a 7-day triple (PPI-amoxicillin-clarithromycin). 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.

The purpose of this study was to determine the effectiveness of the protocol first-line treatment of Helicobacter pylori infection in children (PeptiPac) (omeprazole, clarithromycin, amoxicillin) and evaluating the effectiveness of the scheme, supplemented by bismuth tripotassium ditsitratom.

Patients and Methods

We observed 38 patients (22 boys and 16 girls) aged from 10 to 17 years with a diagnosis of chronic gastritis associated with infection Helicobacter pylori. Diagnosis is based on history, typical complaints, physical examination data, laboratory, endoscopic and morphological studies. 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: duodenal ulcer, intolerance to antibiotics penicillin or macrolides.

All patients were treated with ultrasound in "17 City Children clinical hospital." Esophagogastroduodenoscopy (EGD) with biopsy of the mucosa (SB) of the body and antrum was carried out on the basis of the 2nd CST, 4th CST and DIKB in all patients before eradication therapy. Control endoscopy with biopsy was performed 4-8 weeks after completion of treatment (but not earlier than 2 weeks after discontinuation of PPIs). H. pylori were detected in gastrobioptatah bacterioscopic method, and while testing - and as fast urease method. The success of eradication ascertained in the absence of HP in biopsies and a negative rapid urease test.

In assessing the effectiveness of treatment was calculated percentage rate a cure for the HP-infection of patients in each group. Four 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 one of the II-nd).

Patients were divided into two groups. Children with verified HP infection received one of two patterns of H. pylori therapy (Table 1).

Table 1. Minutes of the first-line eradication therapy

Number
Group

No. of patients

Protocol
eradication

Duration of therapy (days)

I

22

omeprazole, amoxicillin, clarithromycin (KLA-7)

7

II

16

bismuth tripotassium ditsitrat, omeprazole, amoxicillin, clarithromycin (VOAK-7)

7

Research results and discussion

Family history of peptic ulcer disease and gastric cancer was diagnosed in 10 children (26.3%). 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 (in 20 children), rarely observed diskineticheskih (15 patients) and yazvennopodobny (3 people) variants. Tenderness to palpation in the epigastric area and piloroduodenalnoy observed in almost all children.

At endoscopy 37 patients were identified inflammatory changes of CO 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 eight cases. Related dysmotility of the upper gastrointestinal tract: the gastro-oesophageal reflux disease with esophagitis I-II degree was diagnosed in 8 children (21%) of them in 2 cases, there duodeno-gastric reflux.

Histological examination of biopsy specimens of gastric mucosa in 26 patients surveyed (68.4%) was found pangastrit. Isolated antral lesion was observed in 29% (11 patients), gastric body - in 1 patient. According to microscopy, colonization of mucosal HP antrum degree I was diagnosed in 7 patients (18,4%), II degree - in 14 (36.8%) and III degree - in 17 children (44.8%). According to the results of microscopy and rapid urease test in group I observable eradication was achieved in 16 (84.4%), while in the II-nd group - in 14 (93.3%) patients (Table 2).

Table 2. The results of eradication therapy

Number
Group

Number of patients

The effectiveness of the eradication of abs. (%)

HP (-)

HP (+)

I

19

16 (84.4%)

3 (15.6%)

II

15

14 (93.3%)

1 (6.7%)

Side effects leading to cessation of treatment, we observed children were noted. Cases of skin rash or other allergic reactions to administration of drugs were found. Two patients reported an increase in stool frequency to 4 times a day for 2 days, three of them pointed to the sick, and two on a metallic taste in your mouth. The number of side effects was similar in both groups.

Histological examination of biopsy specimens after eradication therapy have shown that after 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 (Table 3).

Table 3. Histological 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 = 38) / after treatment (n = 34)

antral
before treatment (n = 38) / after treatment (n = 34)

abs.

%

abs.

%

Activity of inflammation

-

11/19

28,9 / 55,9

8 / 16

21,1 / 47,1

+

16/12

42,1 / 35,3

11/13

28,9 / 38

+ +

9 / 3

23,7 / 8,8

16 / 4

42/11, 7

+ + +

2 / -

5.3 / -

3 / 1

8 / 3, 2

The intensity of inflammation

-

15/22

39,5 / 64,7

1 / 19

2,6 / 55,9

+

12/10

31,6 / 29.4

4 / 12

10,5 / 35,3

+ +

7 / 2

18,4 / 5,9

23 / 3

60,5 / 8,8

+ + +

4 / -

10.5 / -

10 / -

26.4 / -


Findings

1. The seven-day triple first-line therapy (Peptipak) in children with chronic HF associated diseases kislotozavisimymi provides a high percentage (84.4%) eradication and improve clinical, endoscopic and morphological markers.

2. At a certain rise in price of treatment efficacy eradication increased (p <0.01) for inclusion in the scheme of bismuth tripotassium ditsitrata.

3. Peptipak well tolerated, clinically significant adverse reactions in study groups of children were observed.

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

IE Bovbel, VY Malyugin
"Medical Panorama" 2008, № 3, Art. 57-58

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