helicobacter pylori is a gram - negative , spiral , catalase - positive , and urease - positive bacillus which contributes to a wide range of gastrointestinal ( gi ) and extra - gi diseases ( 1 , 2 ) . h. pylori has gained particular importance nowadays since it has infected about 50% of the world s population .
however , its prevalence is high in developing countries ( 1 , 3 - 5 ) . the most common routes of transmission of the infection are oral - oral , oral - digestive , and fecal - oral contacts ( 6 , 7 ) . the infection has no affinity toward a particular gender ( 8) . this common pathogen can develop chronic gastroenteritis and increase the risk for peptic ulcer and gastric cancer .
therefore , treatment and eradication of the infection is important . according to the conference of maastricht iii ,
the first line of treatment is amoxicillin , omeprazole , and clarithromycin for 7 days which results in an eradication rate of about 80% ( 75% - 98% ) ( 9 - 11 ) .
however , in addition to the 20% resistance of the bacteria to this regimen , cases of drug intolerance and the incidence of adverse events such as diarrhea , abdominal pain , nausea and vomiting , and taste intolerance have been reported .
the second - line treatment is a quadruple regimen including metronidazole and bismuth , which is associated with a high incidence of side effects resulting in drug intolerance ( 12 , 13 ) .
since azithromycin is a macrolide , it reaches a high concentration in the tissue and remains there for a few days after oral administration ; therefore , it can be used in the eradication of h. pylori ( 14 - 18 ) .
the eradication rate of azithromycin used in different regimens has been reported 60% to 80% ( 19 ) . according to a meta - analysis ,
its effect is similar to classical regimen and it is better tolerated by patients ( 19 ) .
the present study aimed to evaluate the effect of classical and azithromycin - containing triple therapy eradication regimen against h. pylori in children , and to determine the level of patients tolerance and drug s side effects .
this single clinical trial was performed in 2014 on 2 to 15 years old children .
volume of the sample was estimated based on past studies ( 20 , 21 ) with 95% confidence and 90% statistical power .
patients were randomly allocated into two age - matched groups by table of random numbers .
h. pylori infection was confirmed through multiple biopsies of the stomach in all children with digestive problems ( including dyspepsia , gastrointestinal bleeding , and chronic abdominal pain ) that needed upper gi endoscopy .
biopsy samples were sent in 10% formalin solution to the laboratory for histological examination . children with consumption of antibiotics in the last two months , allergy to the studied medicines , prior treatment for h. pylori ,
chronic liver and kidney diseases , and simultaneous use of nsaids and other drugs were excluded from the study .
pylori - positive patients were treated alternately with two different drug regimens : group 1 received clarithromycin 7.5 mg / kg / day every 12 hours for 10 days , amoxicillin 50 mg / kg / day every 12 hours for 10 days , and omeprazole 1 mg / kg / day every 12 hours for two weeks .
group 2 received azithromycin 10 mg / kg / day once a day ( before meal ) for 6 days along with amoxicillin and omeprazole .
azithromycin syrup was provided from tehran shimi co. and tablets from kharazmi company , clarithromycin syrup from chemidarou and tablets from rouz darou companies , amoxicillin syrup from farabi company , and omeprazole capsules from abidi company , all in tehran , iran .
a questionnaire has been prepared on the basis of previous studies ( 19 ) that evaluated the drug 's side effects and intolerance and was completed by the patients or their parents .
four to six weeks after completion of treatment , patients stool was tested for h. pylori with monoclonal method using the helicobacter antigen quick kit ( generic assays gmbh , germany ) which has a sensitivity of 85% - 96% and specificity of 83% - 93% ( 22 - 24 ) .
the study was approved by the ethics committee of the babol university of medical sciences ( clinical trial registration number irct2013112115475n1 ) , and informed consent was obtained from the parents .
the collected data were analyzed using spss-20 through comparison of recovery level and side effects between the two treatment methods with chi - square test , fisher s exact test , and t - test .
the regimens were analyzed with the methods itt ( intention to treat ) and pp ( per protocol ) .
the study was performed on two groups consisting of 32 members receiving either omeprazole - clarithromycin - amoxicillin ( oca ) or omeprazole - azithromycin - amoxicillin ( oaa ) regimens .
the baseline characteristics of patients are depicted in table 1 . as shown in the table
, there were no significant differences between the two groups regarding gender distribution and mean age of the patients .
abdominal pain with and without nausea and vomiting was the most common cause of endoscopy in the two study groups .
endoscopic findings of the patients are shown in table 1 . as can be seen , antral nodularity was the most common endoscopic finding in the patients .
the therapeutic response to the oca and oaa regimens are depicted in table 2 . based on itt analysis , the therapeutic response in the oaa and oca
as shown in the table , there was no significant difference between the two groups regarding the rate of side effects .
the therapeutic response in the two treatment groups in terms of gender is presented in table 3 .
as can be seen , no significant difference was found between the two treatment groups in therapeutic response regarding gender .
eradication of h. pylori with classic triple therapy in children may be associated with intolerance and complications from clarithromycin .
its replacement with other macrolides ( azithromycin ) with shorter treatment time and lower dose can reduce these side effects with the same eradication effect . according to the results of itt analysis ,
the therapeutic response was seen in 56.2% of the oaa group and 62.5% of the oca group with no statistically significant difference between them . in other words ,
the therapeutic response was observed in more than half of the patients in both treatment groups . in a study conducted by sarkeshikian et al .
( 25 ) , 165 adult patients with symptoms of dyspepsia were divided into two groups ; the first group ( 89 patients ) was treated with omeprazole , amoxicillin , and azithromycin and the second group ( 76 patients ) with amoxicillin , omeprazole , and clarithromycin . according to the breath test performed 6 weeks later ; the eradication rate was 75% in the first group and 82% in the second group , and there was no statistically significant difference between the two groups ( 25 ) .
this study was consistent with our study regarding the lack of significant difference in the therapeutic response between the two groups .
although this study was conducted in adults , the therapeutic response in each group was individually higher than in the present study . in a study conducted in virginia , usa , by sullivan et al .
( 26 ) , 56 adult patients with gi symptoms and with h. pylori confirmed by endoscopy were enrolled in the study and divided into two groups of 27 patients ( treated with bismuth , lansoprazole , amoxicillin , and clarithromycin ) , and 29 patients ( treated with bismuth , lansoprazole , amoxicillin , and azithromycin ) .
the pp analysis results showed an eradication rate of 84.6% in the first group and 55.5% in the second group , with a statistically significant difference between them ( 26 ) .
although this study was performed in adults , it had two other differences with the present study ; first , the therapeutic response was higher ; second , the therapeutic response observed in clarithromycin group was higher than in azithromycin group . in a study by bahremand et al .
( 27 ) entitled  evaluation of the effectiveness of triple and quadruple therapy regimens for eradication of helicobacter pylori in children referred to imam khomeini hospital , tehran ,  patients with h. pylori infection determined by histological examination were divided into two groups .
the triple - drug regimen included amoxicillin ( 50 mg / kg / day ) , omeprazole ( 1 mg / kg / day ) , clarithromycin ( 15 mg / kg / day ) , and the quadruple regimen included omeprazole ( 1 mg / kg / day ) , amoxicillin ( 50 mg / kg / day ) , metronidazole ( 20 mg / kg / day ) , and bismuth citrate ( 8 mg / kg / day ) for 10 days .
patients were assessed by urea breath test 4 weeks after treatment , which showed eradication of h. pylori in 92% of the triple therapy group and 84% of the quadruple therapy group ( 27 ) .
the reason for the difference in results between the two studies may be related to the fact that previous study was done over a decade ago , so an increase in antimicrobial resistance over time may have decreased treatment success rate in our study . during 1995 - 1996 in japan
, kato et al . ( 28 ) studied 22 patients of 8 to 16 years of age who had active lesions and confirmed h. pylori infection .
they had undergone eradication therapy in which 10 patients received double - drug regimen of omeprazole ( 1 mg / kg bid ) and amoxicillin ( 30 mg / kg bid ) , and 12 patients received triple - drug regimen of clarithromycin ( 15 mg / kg bid ) along with omeprazole and amoxicillin for 14 days .
differences between results of the present study and other studies can be attributed to various factors , for example , this study was conducted in children , whereas most studies were performed in adults .
antimicrobial resistance and diversity of h. pylori in children ( 29 - 34 ) are the key factors in the failure of anti - h .
pylori regimens ( 35 , 36 ) , which may be caused by indiscriminate and arbitrary use of antibiotics in iran , especially azithromycin , which is highly used for different infections including respiratory infections . according to a meta - analysis
, there is no ideal first or second - line treatment for achieving 100% eradication .
the therapeutic order should be carried out according to the initial treatment and local antimicrobial resistance studies .
the common endoscopic finding was nodularity in antrum that had no effect on treatment response ; the two groups did not differ in this respect . in agreement with ours , study of rafeey
et al . showed the most common finding was nodularity in antrum and there was no relationship between the genotypes of h. pylori that is effective in the response to treatment , with endoscopic findings ( 37 ) .
the results of this study showed that the rate of drug intolerance in the oca and oaa groups was 9.4% and 3.1% , respectively , with no significant difference between them and no major adverse effects in either treatment groups .
minakari et al . in 2010 evaluated a quadruple therapy including azithromycin or clarithromycin as the second - line therapy .
the rate of intolerance to the regimen was 3.5% in the azithromycin - receiving group and 4.3% in the clarithromycin - receiving group , and there was no significant difference between them ( 38 ) .
this is similar to the present study ; however , compared to the present study , the rates of intolerance in both groups were lower in patients who received the second - line treatment .
this study showed that eradication of h. pylori with classic triple therapy in children with complications of clarithromycin , can be used azithromycin as other macrolide with a shorter time .
since the response rate was lower than ideal in both regimens , it is suggested to carry out studies with more patients and newer regimens , and to determine the rate of antimicrobial resistance in comparison with clarithromycin .
 background and objectives : the present study aimed to evaluate the effect of classical and azithromycin - containing triple therapy eradication regimen against h. pylori in children , and to determine the level of patients tolerance.patients and methods : this single clinical trial was performed in 2014 on 2 to 15 years old children . 
 all children , in whom h. pylori infection was confirmed through multiple biopsies of the stomach and required treatment , were enrolled in the study . 
 h. 
 pylori - positive patients were treated alternately with two different drug regimens ; group oca received clarithromycin 7.5 mg / kg / day every 12 hours for 10 days , amoxicillin 50 mg / kg / day every 12 hours for 10 days , and omeprazole 1 mg / kg / day every 12 hours for two weeks , and group oaa received azithromycin 10 mg / kg / day once a day ( before meal ) for 6 days along with amoxicillin and omeprazole . 
 four to six weeks after completion of treatment , patients stool was tested for h. pylori through the monoclonal method using the helicobacter antigen quick kit.results:there were no significant differences between the two groups regarding gender and age of patients . 
 based on itt analysis , the therapeutic response in the oaa and oca groups were 56.2% and 62.5% , respectively ( p = 0.40 ) . 
 drug adverse effects were 15.6% in the oca and 3.1% in the oaa group ( p = 0.19).conclusions : the therapeutic response was seen in more than half of the patients treated with triple therapy of h. pylori eradication regimen including azithromycin or clarithromycin , and there was no significant difference between the two treatment groups . 
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion