EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS AND OUTCOMES OF TREATMENT REGIMENS FOR PEDIATRIC PEPTIC ULCER DISEASE CAUSED BY DRUGRESISTANT HELICOBACTER PYLORI AT NATIONAL PEDIATRIC HOSPITAL

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MINISTRY OF EDUCATION AND
MINISTRY OF
TRAINING
HEALTH
NATIONAL INSTITUTE OF HYGIENE AND
EPIDEMIOLOGY

NGUYEN THI UT

EPIDEMIOLOGICAL AND CLINICAL CHARACTERISTICS
AND OUTCOMES OF TREATMENT REGIMENS FOR
PEDIATRIC PEPTIC ULCER DISEASE CAUSED BY DRUGRESISTANT HELICOBACTER PYLORI AT NATIONAL
PEDIATRIC HOSPITAL

Specialty: Epidemiology
Code: 62.72.01.17

SUMMARY OF MEDICINE PHD THESIS

HANOI – 2016
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This work has been completed at
the National Institute of Hygiene And Epidemiology

Instructors:
1. Le Thanh Hai, Associate Professor, Ph.D
2. Hoang Thi Thu Ha, Ph.D

Reviewer 1: Hoang Huy Hau, Associate Professor, Ph.D.
Reviewer 2: Nguyen Gia Khanh, Professor, Ph.D
Reviewer 3: Pham Van Trong, Associate Professor, Ph.D

The Thesis will be defended at the Institute level Council for
Thesis Performance Appraisal convened at the National Institute
of Hygiene And Epidemiology.
On:
date
month
year 2016

The Thesis could be found at:
1. The National Library
2. The Library, National Institute of Hygiene And
Epidemiology
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1. INTRODUCTION
Peptic ulcer disease (PDU) caused by Helicobacter pylori (H.
pylori) was a rather common condition in the world. H. pylori
had been considered a major cause of chronic gastritis (77.4 77.9%); duodenal ulcer (>95%) and stomach ulcer (>75%).
Treatment of H. pylori PDU was difficult, and treatment regimen
outcomes depended very much on antibiotics - provided with
high drug resistance, treatment effectiveness used to be lower
than desired levels (<80%). Understanding of H. pylori PDU
epidemiological and clinical characteristics, and therapeutic
antibiotic efficacy could help clinicians and managers act more
effectively in prevention and treatment. So far, in Vietnam, there
had not been any study on H. pylori epidemiological, clinical and
toxicological characteristics; and effectiveness of treatment for
pediatric PDU caused by drug-resistant H. pylori. Therefore, we
carried out the research on “Epidemiological and clinical
characteristics and outcomes of treatment regimens for pediatric
peptic ulcer disease caused by drug-resistant Helicobacter pylori
at National Pediatric Hospital, October 2011 to November 2013”.
Specific objectives of the research were:
1. Epidemiological and clinical characteristics of pediatric
peptic ulcers disease caused by drug-resistant H. pylori at
National Pediatric Hospital, from October 2011 to November
2013, described.
2. Drug resistance levels and related factors in children with
PDU determined.
3. Drug-resistant H. pylori clearance effects of some
treatment regimens for pediatric PDU cases described.
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2. NEW SCIENTIFIC CONTRIBUTIONS
 This was one of comprehensive researches on epidemiology,
clinical features and treatment of drug-resistant H. pylori
PDU in children, Vietnam, with a relatively large number of
pediatric patients.
 The research had used molecular biology techniques, namely
PCR and RAPD to identify toxic genes of bacteria, and the
transmissibility in the family.
 This was one of researches that simultaneously used both 4
drug and 3 drug treatment regimens to treat pediatric H. pylori
PDU.
3. PRACTICAL VALUES OF THE THESIS
- Results on epidemiological and clinical characteristics of drugresistant pediatric H. pylori PDU helped physicians visualize its
drug resistance. Disease related information orientated them to
PDU.
- The research had also found 4 drug treatment regimen effective
and safe in the treatment of drug-resistant H. pylori PDU.
4. THESIS STRUCTURE
The thesis included 146 pages: introduction (2 pages),
overview (45 pages), research subjects and methodology (20
pages), results (37 pages), discussion (39 pages), conclusion (2
pages), and recommendation (1 page), with 42 tables, 5 figures,
18 charts, and 219 reference documents including 24 Vietnamese
and 195 English ones.
CHAPTER 1: OVERVIEW
1.1. PDU epidemiological and clinical characteristics, and

drug-resistant H. pylori
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1.1.1. Definition: Gastritis is a term referring to all inflammatory
lesions in the gastric mucosa, demonstrating response of the
gastric mucosa to attacking elements. Gastro-duodenal injuries
when deeply impregnated through the muscular layer of stomach
or duodenal membranes would lead to ulcers.
1.1.2. H. pylori research history
In 1984, H. pylori was successfully isolated by Marshall and
Warren; this finding had been official published in The Lancet
(1984). Recently, the role of H. pylori in PDU pathogenesis, its
antibiotic resistance, and treatment regimens had been mentioned
in many international and national conferences.
1.1.3. H. pylori PDU epidemiological characteristics
1.1.3.1. Etiology and transmission sources
H. pylori is a gram-negative bacterium with helical shape. It
is a major cause of active chronic gastritis and gastric ulcers, and
a risk for gastric cancer. H. pylori transmission source is mainly
human being.
1.1.3.2. Modes of transmission
- Mouth-to-mouth, fecal-oral, gastro-oral transmission routes.
- Family transmission was found by many studies.
1.1.3.3. Susceptible population
H. pylori could co-exist with the host for decades without

symptoms. Once infected with H. pylori, patients may suffer
from gastritis, stomach ulcers, and stomach cancer.
1.1.3.4. Disease frequency
Frequency of H. pylori PDU varies very much from country
to country and from age group to age group. Generally it is
higher in developing countries and lower in developed countries.
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Incidence of gastroenteritis is age dependent.
PDU is a problem of 1-1.5% children; it is often primary,
mostly chronic and localizes in the duodenum; its main cause is
H. pylori infection (about 80%) or unknown (about 20%). About
10 to 15% people infected with H. pylori would develop PDU
and 1% would develop stomach cancer.
1.1.4. Pathogenesis
In the acute phase, bacteria invade, multiply and cause
mucosal inflammation. In the chronic inflammatory phase,
manifestation is clear with tissue changes, peeling mucosa and
multiple inflammatory cell infiltration; mucosal barrier is
destroyed, leading to scratches and ulcers.
1.1.5. Immunology
After being infected with H. pylori, the host would develop a
very strong local and systemic immune response. Despite of this
immune response, infection may still exist throughout the life.
1.1.6. Clinical manifestations

H. pylori infection could lead to symptoms in the
gastrointestinal tract or digestive system. Recurrent abdominal
pain is a common clinical sign – up to 87-96%; abdominal pain
could be localized in the epigastric region, or persists around
the navel and is associated with meals. Nausea and vomiting are
two common signs in children under 3 years old. Older children
often suffer from gnawing, shortness of breath, bloating and
discomfort.
Peptic ulcer: H. pylori infected children often have no
symptom; only a small portion develops ulcerative PDU. H.
pylori is found in 90% of children with ulcerative PDU, and it is
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proved that ulcers would be healed after H. pylori clearance.
1.1.7. Methods of diagnosing H. pylori PDU
1.1.7.1. Diagnostic methods
 Non-invasive methods
+ Serological test: mainly applied for epidemiological
studies.
+ Breath test (UBT): allows determining H. pylori infection
based on bacterial urea hydrolysis. Carbon marking could use
C13.
+ Stool antigen test: accuracy of the test using monoclonal
antibodies is higher than of polyclonal antibodies.
• Invasive methods

+ Endoscopy: to determine H. pylori gastritis through images
- normal; inflammation; nodules with lumpy granular; new, still
bleeding shallow scraped or deep ulcers; or old and scarring
ulcers.
+ Rapid urease test (CLO test): allows determining the
presence of H. pylori.
+ Histopathology: helps detect bacteria and evaluate peptic
mucosal lesions
+ Bacterial culture
Culturing is considered the gold standard method with 100%
specificity. Culturing verifies and identifies H. pylori antibiotic
resistance.
+ H. pylori antibiotic susceptibility test:
- Diffusion test: suspension of 108 CFU / ml bacteria cultured
in the Mueller – Hinton agar media containing 10% horse blood,
then put standardized antibiotic paper discs on its surface. Results
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are calculated following diameter of the sterile round generated.
+ Molecular biology methods
PCR method amplifies duplicate strings, helps determine the
presence of bacterial toxic genes such as cagA and vacA.
RAPD (Random Amplified polymorphic DNA) – a method
for multifold analysis of randomly amplified DNA. RAPD helps
identify differences between different bacterial strains. Genomes

of two different strains give different footages on the genes for
comparison of bacteria’s biodiversity.
1.1.7.2. Diagnosis of H. pylori PDU
 Criteria for H. pylori PDU diagnosis:
+ Endoscopy test is used to diagnose peptic ulcer according
to Sydney classification system.
+ Histopathological test is used to diagnose gastritis.
H. pylori infection is diagnosed when present one of the
following conditions:
- H. pylori (+) in histopathological and urease tests.
- H. pylori (+) in culture of gastric biopsy piece.
1.2. Antibiotic-resistant H. pylori and risk factors of PDU
1.2.1. Concept of antibiotic resistance
1.2.1.1. H. pylori primary antibiotic resistance
This is the status when a child has not been previously treated for
clearing H. pylori; antibiotic resistance is the consequence of
using antibiotics to treat his/her other diseases. A small number
of patients received drug-resistant strains from others.
1.2.1.2. H. pylori secondary antibiotic resistance

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This is the status when H. pylori antibiotic resistance appears in
patients who have been previously treated for H. pylori
clearance.

1.2.2. Antibiotic resistance and virulence of bacteria
1.2.2.1. VacA gene related cytotoxic factors
VacA is an important toxin presented in almost all strains of
H. pylori. VacA contains diverse alleles that vary from one to
other H. pylori strain. VacA genotype s1 / m1 is the most toxic
combination, while s2 / m2 and m2 / s1 are nontoxic.
1.2.2.2. CagA gene related cytotoxic factors
CagA is a toxic protein of H. pylori, encoded by cagA gene.
CagA (+) is more often associated with peptic ulcer, atrophic
hypertrophic gastritis and adenocarcinoma than strains cagA (-).
Taneike had found that 68% strains contained cagA (+),
metronidazole resistance rates among cagA (-) group was higher
than of cagA (+) (P = 0.0089).
1.2.3. H. pylori antibiotic resistance rate and risk factors
- H. pylori antibiotic resistance is the main cause of treatment
failure. Worldwide, antibiotic resistance rate is increasing and
varies from region to region. Developing countries faces a higher
antibiotic resistance rate than developed ones. This rate of
clarithromycin is > 20% in the US and other developed countries
in Europe and Asia.
1.2.5.1. Clarithromycin resistance rate
Clarithromycin resistance rate among children is 50.9% in
Vietnam.
1.2.5.2. Azithromycin resistance rate

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Azithromycin resistance ranges is high in children; it varies from
17.9% in Croatia to 87.7% in Beijing.
1.2.5.3. Metronidazole resistance rate
In Vietnamese children, metronidazole resistance rate is
65.3%; this is increased with age, higher in urban than in rural
areas, and more common in boys.
1.2.5.4. Amoxicillin resistance rate
In Europe, resistance rate is low at 0-2%. However, high rate
had been seen in some countries of Africa and Asia – among
children of Iran it was 59%. In Vietnam, the rate of 2006 was
0.5%.
1.2.5.5. Tetracycline resistance rate
Tetracycline resistance has not been seen, or seen at very low
rate in most countries (0-5%). The rate among Italian and
Bulgarian children was 3%.
1.2.5.6. Quinolone resistance rate
Primary resistance rate in children is low (2-7%). High
resistance usually involves increased use of new quinolone
generations. Ciprofloxacin primary resistance in Italian children
in 2005 accounted for 6%. Levofloxacin resistance among
Beijing children was rather high - 13.7%.
1.2.5.8. Resistance to two or more antibiotic classes
Rate of resistance to two antibiotics classes is <10% in
Europe, Asia and North America. Rate of resistance to both
amoxicillin and clarithromycin among children of Iran is 14.5%.
This rate for both clarithromycin and metronidazole among
children of Vietnam is 28.8%.
1.3. Treatment of H. pylori PDU

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1.3.1. Indications for treatment
Antibiotic treatment is applied to all H. pylori (+) PDU;
children with endoscopy diagnosed lesions and H. pylori (+)
whose father/mother had H. pylori ulcers/stomach cancer;
children with iron deficiency anemia who are not successful with
treatment, or with autoimmune thrombocytopenia.
1.3.2. Treatment drugs
1.3.2.1. Secrete preventing drugs
Proton pump inhibitors (PPI)
Omeprazole: Rapidly and effectively inhibits acid after an oral
dose.
1.3.2.2. Antibiotics
Amoxicillin: is an antibiotic that effectively clears H. pylori by
destroying bacterial cell walls, leading to its destruction.
Metronidazole: is an osmotic drug that enters bacterial cells and
causes its DNA damage, thus destroys it.
Clarithromycin: impacts on transfer RNA and 50S ribosomal
subunit, disordering bacterial protein synthesis, thus destroys it.
Bismuth salt:
This has a direct bactericidal effect thanks to the agglomeration
of crystals inside and on the bacterial cell walls, condensing
bacterial cell vacuoles.
CHAPTER 2

RESEARCH SUBJECTS AND METHODOLOGY
2.1 Research Subjects
2.1.1 Research Subjects
Pediatric patients 2 to 16 years old diagnosed with H. pylori
PDU, examined and treated at the National Institute of Pediatrics
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from October 2011 to November 2013.
2.1.2. Inclusion criteria
Patients meeting the following criteria:
- Clinical: symptoms of gastroduodenal pathology, indicated
for gastrointestinal endoscopy, including recurrent abdominal
pain, nausea, vomiting, bloating, indigestion and epigastric
burning or gastrointestinal bleeding, and unexplained anemia.
- Testing:
+ Endoscopy: images of inflammatory lesions or peptic
ulcers
+ Histopathology: patients with inflammatory lesions
+ Bacterial culture: growth and antimicrobial susceptibility
obtained
- Treatment: Patients who have not been treated with
antibiotics, proton pump inhibitors and antacids within 1 month
before being undergone endoscopy; and have no history of PDU
treatment.
- Families and patients agree to participate in the research

with full adherence; and to come for check ups on time.
2.1.3. Exclusion criteria
- Patients with other infections and serious illnesses.
- Patients having undergone gastric operation(s) and been
allergic to antibiotics.
2.2. Research sites
- Epidemiological and clinical studies performed at the
Department of Gastroenterology; and Outpatient Clinics –
National Pediatric Hospital.
- Paraclinical studies performed at the Department of
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Bacteriology - National Institute of Hygiene and Epidemiology,
and Departments of Endoscopy and of Pathology - National
Pediatrics Hospital.
2.3. Research time
From October 2011 to November 2013.
2.4. Research Methodology
2.4.1. Design: 2 designs used
- Cross-sectional descriptive study with appropriate analysis
- Treatment assay without control groups, describing results
of 2 treatment regimens.
2.4.2. Sample size and sampling method
2.4.2.1 Sample size and sampling method for Objectives 1 and 2
+ Sample size: total patients meeting inclusion criteria during 2

years, from October 2011 till November 2013.
To respond to the 1st Objective, 588 eligible children diagnosed
with PDU caused by antibiotic-resistant H. pylori were enrolled
in the research.
For the 2nd Objective, 624 eligible children diagnosed with H.
pylori PDU were studied on antimicrobial susceptibility
(including non-resistant and resistant cases).
+ Sample selection:
Children aged 2 years to 16 years, initially diagnosed with
suspected PDU, admitted to the National Pediatric Hospital, were
explained about the research purpose and contents. Once families
had agreed to participate, doctors asked their history, performed
PDU physical examination, endoscopy, biopsy, urease test,
dyeing H. pylori shed for histopathology, and culture for H.
pylori bacteria, then antimicrobial susceptibility test to determine
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drug resistance. Cases diagnosed with H. pylori(+) PDU resisting
to at least 1 in 8 antibiotics: amoxicillin, clarithromycin,
metronidazole, ciprofloxacin, tetracycline, azithromycin,
levofloxacin and cefixime had been enrolled into the research.
+ Other samples
To determine the possibility of cross-infection within family
through studying genotype of isolated H. pylori strains, we
selected 17 representative households participating in the study

using a convenient sample.
To determine association between the antibiotic resistance
and the presence of genes CagA and VacA in H. pylori strains
isolated from patients infected with antibiotic-resistant H. pylori,
we selected for analysis 150 H. pylori strains by sampling
conveniently, of which 50 resisted to amoxicillin, 50 to
clarithromycin and 50 to metronidazole.
2.4.2.2. Sample size and sampling for the 3rd Objective
+ Sample size: based on total patients eligible for inclusion
into the research during 2 years, from October 2011 until
November 2013, including PDU patients caused by H. pylori
resisted to at least 1 antibiotic drug, who agreed to participate and
comply with treatment regimens prescribed. 195 patients were
included in the list of treatment. They were divided into 2 groups:
(i) Group 1 with 97 patients, receiving 4 medicines recommended
by the Association of Pediatric Gastroenterology and
Hepatobiliary of Europe and North America, Maastrich IV; (ii)
Group 2 included 98 patients eligible for regimen with 3 drugs
following their antimicrobial susceptibility, based on the routine
treatment guidelines of National Pediatric Hospital.
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+ Sampling method: According to the convenient sampling,
all subjects positive with H. pylori and resistant to antibiotics,
whose families provided informed consent and committed to

comply with treatment requirement were enrolled.
CHAPTER 3: RESULTS
3.1. Several epidemiological and clinical characteristics of
PDU caused by antibiotic-resistant H. pylori
3.1.1. Several epidemiological characteristics
3.1.1.1 Rate of pediatric PDU caused by antibiotic-resistant H.
5,8%
kháng KS
pylori (A-R)
không kháng KS
94,2%

Figure 3.1. Distribution of PDU cases with antibiotic-resistant
H. pylori at National Pediatric Hospital (n=624)
From 624 pediatric H. pylori PDU patients examined and
treated (October 2011 - November 2013), 588 found with
antibiotic-resistant H. pylori (94.2%).
3.1.1.2. Distribution of antibiotic-resistant H. pylori PDU by age
group
Figure 3.2. Distribution of antibiotic-resistant H. pylori PDU by
age group (n=588)
This distribution showed that the youngest was 2 years old
and the highest was 16 years old; average age was 7.29 ± 2.16;
the highest proportion was in 6-9 years group (54.9%).
3.1.1.3. Distribution of antibiotic-resistant H. pylori PDU by sex
Figure 3.3. Distribution of antibiotic-resistant H. pylori PDU
by sex (n=588)
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49.5% was male; this was equivalent to the proportion of
females, 50.5%.
3.1.1.4. Gastric and duodenal history of patients’ family
Figure 3.4. Gastric and duodenal history of patients’ family
(n=588)
Figure 3.5 showed that 72.3% pediatric patients came from
families with PDU history, and 27.7% without this history.
3.1.1.5. History of antibiotic treatment
Figure 3.5 - History of antibiotic treatment for other diseases
(n=588)
The result showed that proportion of patients who used
antibiotic treatment for other diseases was 71.8%, and who had
not used them was 28.2%.
3.1.1.6. H. pylori transmission in the family
 General information about research subjects
In this study, we had selected 17 households with H. pylori
patients. 50 H. pylori strains were isolated from patients and
family members, of those 17 were from pediatric patients, 33
from family members including fathers, mothers and
brothers/sisters.
 Genotypic analysis of H. pylori strains isolated from patients
and family members:
All 50 H. pylori strains were analyzed by RAPD technique.
Results showed that 46.1% (6/13) mothers had genotypes similar
to the ones of their children. In contrast, only 8.3% (1/12) fathers
had genotypes similar to the ones of their children. 11.8% (2/17)

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H. pylori strains of pediatric patients were similar to the ones of
their brothers/sisters.
3.1.2. Several clinical and paraclinical characteristics
3.1.2.1. Clinical characteristics
Figure 3.6 - Clinical characteristics of antibiotic-resistant H.
pylori PDU
Figure 3.6 showed that abdominal pain was the most common
symptom, it accounted for 96.9% cases; anorexia 59.5% was also
common. Symptoms of vomiting, belching, heartburn, bloating
occupied respectively 46.9%; 29.3%; 18.7%; 19.2% and 6.1%.
3.1.2.2. Paraclinical characteristics
 Gastroscopic images of injury

Figure 3.7. Gastroscopic images of injury (n=588)
Endoscopic images showed that edema and congestion were the
most common phenomena, accounting for 94.2% cases; lumpy and
granular lesions occupied 69.9%. PDU presented only in 5.8%
patients.
Figure 3.8. Locating gastroduodenal lesions by endoscopy (n
= 588)
Endoscopic images showed that antral gastritis alone occupied
31.8% of 187 pediatric patients; whole gastric lesions presented
in 57.1% of them.

Table 3.1. Histopathological characteristics of antibioticresistant H. pilori PDU
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Histopathological
Number
Proportion
characteristics
(n=588)
%
Location of lesion
Body of stomach
7
1,2
Antrum of stomach
36
6,1
Whole stomach
545
92,7
Histopathological lesions were mainly whole stomach
inflammation (92.7%), moderate and severe gastritis occupied
78.6%.
3.2. Levels of antibiotic resistance, and factors related to
antibiotic resistance in H. pylori PDU children
3.2.1. Antibiotic resistance of H. pylori strains

Out of 624 H. pylori strains isolated, 5.8% were sensitive, 59.8%
were resisted to 2 or more antibiotics, and 215 strains (34.4%)
resisted to 1 antibiotic (Figure 3.9)
Figure 3.9. Level of antibiotic resistance, H. pylori strains (n =
624)
3.2.2. General resistance of H. pylori to antibiotics
Table 3.2. Resistance of H. pylori to each antibiotic (n=624)
Sensitive
Medium
Resistant
Antibiotic
N
%
n
%
n
%
Clarithromycin 238
38.1
33
5.3
353
56.6
Azithromycin
265
42.5
11
1.8
348
55.8

Metronidazole 423
67.8
19
3
182
29.2
Amoxicillin
479
76.8
31
5
114
18.3
Cefixime
548
87.8
4
0.6
72
11.5
Ciprofloxacin 597
95.7
16
2.6
11
1.8
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Tetracycline
621
99.5
0
0
3
0.5
Levofloxacin
603
99.3
2
0.3
2
0.3
Resistance to clarithromycin was the most serious with the
highest proportion of 56.6%. Resistance to azithromycin,
metronidazole, amoxicillin, and ciprofloxacin cefixime were
respectively 55.8%, 29.2%, 18.3%, 11.5% and 1.8 %.
3.2.3. Multidrug resistance of H. pylori isolated
Table 3.3. Resistance to two or more antibiotics (MDR)
Antibiotic
No. resistant
%
strains (n=624)
CLA + AZ
191
30.6

MTZ + AZ
112
17.9
CLA + MTZ
61
9.8
AMX + CLA
57
9.1
AMX + MTZ
25
4.0
MTZ + CLA + AZ
41
6.6
AMX + CLA + AZ
16
2.6
CLA + AZ + CIP
1
0.2
MTZ + CEF + CLA +
4
0.6
AZ
Resistance to two antibiotics - azithromycin and clarithromycinis
- was the highest (30.6%). 9.1% H. pylori strains resisted to both
amoxicillin and clarithromycin. Resistance to 3 antibiotics azithromycin+ clarithromycin + metronidazole - was 6.6%.
Resistance to 4 antibiotics - azithromycin + clarithromycin +
metronidazole + cefotaxime - was 0.6%.

3.2.4. Distribution of antibiotic resistance
Table 3.4. Distribution of antibiotic resistance by sex (n=624)
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Sex

20

Male
(n=305)
n
%
187
61.3

Female
(n=319)
n
%
166 52.0

P

Antibiotic
Clarithromycin
0.019a
(n=353)
Amoxicillin

52
17.0
62
19.4 0.441a
( n=114)
Metronidazole
90
29.5
92
28.8 0.854a
(n=182)
Ciprofloxacin
5
1.6
6
1.9 0.531a
(n=11)
Azithromycin
168
55.1 180 56.4 0.735a
(n=348)
Tetracycline (n=3)
2
0.7
1
0.3 0.616b
Levofloxacin (n=2)
1
0.3
1

0.3
1.00b
Cefixim (n=72)
40
13.1
32
10.0 0.228a
a. Chi-squared test
b. Fisher’ Exact test
Resistance to clarithromycin was higher in men (61.3%) than
in female (52%), the difference was statistically significant with
P <0.05. For other antibiotics, there was no sex difference, P >
0.05.
3.2.5. Factors related to resistance to one antibiotic
Two 2 groups of children with H. pylori PDU – one was
sensitive to antibiotics (36 patients) and the other was resisted to
some antibiotic (215 patients) - were analyzed to determine
related factors.

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Table 3.5 Relationship between age, sex and place of
residence with resistance to 1 antibiotic
Resisted to
Sensitive to

1 antibiotic
antibiotics
Characteristic
OR
(n=215)
(n=36)
of subjects
(95% CI)
n %
n
%
<5
60
82.2
13
17.8 0.66 (0.22-2.06)
Age
6-9
120 87.0
18
13.0 0.95 (0.33-2.74)
≥10
35
87.5
5
12.5
1.00
M
106 88.3
14

11.7 1.53 (0.74-3.14)
Sex
F
109 83.2
22
16.8
1.00
Hanoi 128 84.2
24
15.8 0.73(0.35- 1.55)
Location
Other 87
87.9
12
12.1
1.00
Results showed no (statistically significant) association
between those who developed resistance to 1 antibiotic and who
remained sensitive to antibiotics regarding age, sex and place of
residence.
3.2.6. Factors related to multidrug resistance
Further, comparison of two groups of children with H. pylori
PDU, one sensitive to antibiotics (36 patients) and the other
resisted to 2 or more antibiotics (MDR) (373 patients) was done
to identify relevant factors.
Table 3.6. Relationship between age, sex and place of
residence multiple-drug resistance
Sensitive
MDR
to

OR
Characteristic
(n=373) antibiotics
(95%CI)
(n=36)
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2-5
Age
6-9
≥10
M
Sex
F
Hanoi
Location
Other

n

%

n

%

92
203
78
185
188
234
139

87.6
91.9
94.0
93.0
89.5
90.7
92.0

13
18
5
14
22
24
12

12.4
8.1
6.0
7.0
10.5

9.3
8.0

2.20 (0.75-6.45)
1.38 (0.49-3.85)
1.00
1.55 (0.77-3.11)
1.00
0.84 (0.41-1.74)
1.00

Table 3. 6 showed no statistically significant relationship
between age group, sex, and geographical location with multiantibiotic resistance.
3.2.7. Some factors associated with clarithromycin resistance
In this study, H. pylori resistance to clarithromycin was the
highest (56.6%), following by metronidazole (29.2%). Both were
widely used in treatment, therefore, we focused on studying factors
related to H. pylori resistance to these 2 antibiotics.
Table 3.7. Several factors related with resistance to
clarithromycin
Medium
Resisted
and
AOR(95%CI)
UOR
Characteristic
sensitive (95%CI)
n (%)
n (%)
1.46*

1.42**
Male
187 (61.3) 118 (38.7) (1.06(1.02-1.98)
Sex
2.01)
Female 166 (52.0) 153 (48.0)
1.00
2.45**
Antibiotic
Yes
2.16*
277 (62.0) 170 (38.0)
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history

23

(1.52(1.69-3.55)
3.08)
No
76 (42.9) 101 (57.1)
1.00
3.12*
Yes
27 (79.4)
7 (20.6)
(1.343.06**

PDU
7.29)
No
326 (55.3) 264 (44.7)
1.00
(1.27-7.36)
(* Not adjusted), (** Multivariate analysis, adjusted for age
and sex)
Note: * statistically significant (95% confidence interval did
not contain the value 1)
Table 3.22 showed that boys were at 1.46 time higher risk of
resisting to clarithromycin than girls with 95% CI = (1.06 - 2.01).
Children with a history of clarithromycin use had the risk of
resistance at 2.16 time higher; 95% CI = (1.52 - 3.08). Stomach
ulcer was at 3.12 time higher risk of resisting to clarithromycin
with 95% CI = (1.34 - 7.29).
3.2.8. Some factors associated with resistance to metronidazole
Table 3.8. Some factors associated with resistance to
metronidazole
Medium
Resisted and
OR
Characteristic
sensitive
(95%CI)
n
%
n
%
<5

49 29.7 116
70.3 0,92(0,54-1,55)
Age
6-9
100 29.3 241
70.7 0,93(0,59-1,49)
≥10
33 28.0
85
72.0
1,00
Sex
M
90 29.5 215
70.5
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24

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Antibiotic
history

PDU

F
Yes

28.8

227

71.2

121 27.1

326

72.9

No

61

34.5

116

65.5

Yes

8

23.5

26

76.5

No

92

1,46)
1,00
0,71 (0,491,03)
1,00
0,74 (0,331,66)
1,00

174 29.5 416
70.5
Total
182 29.2 442
70.8
Table 3.8 showed that there was no association between
metronidazole resistance and related factors such as family’s
PDU history, and antibiotic use history.
3.2.9. Association between antibiotic resistance and the
presence of cagA and vacA in H. pylori antibiotic-resistant
strains
150 samples of H. pylori isolated from 150 infected pediatric
patients whose antimicrobial susceptibility showed a resistance to
at least 1 of 3 antibiotics - amoxicillin, clarithromycin and
metronidazole – were studied on cagA and vacA genes.
Relationship between the presence of cagA and vacA genes and
amoxicillin resistance

Figure 3.10. Amoxicillin resistance by gene
There was no statistically significant difference regarding the
rate of cagA and vacA between 2 groups of amoxicillin resistance
and susceptibility (P>0,05).
Relationship between the presence of cagA and vacA genes and
clarithromycin resistance
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25

Figure 3.11. Clarithromycin resistance by gene
In the clarithromycin resistant group, 34.1% had cagA; in the
other, sensitive group, this was 33.9%. There was no statistically
significant difference regarding rates of cagA and vacA between
2 groups (P > 0.05).
Relationship between the presence of cagA and vacA genes and
metronidazole resistance
Figure 3.12. Metronidazole resistance by gene
CagA positive H. pilori occupied 33.8% of the metronidazole
resistant group, but no difference was detected between this and
the sensitive group (34.1%). Among 65 of metronidazoleresistant strains, vacAs1, vacAs2, vacAm1, and vacAm2 were
respectively 43.1%, 12.3%, 38.3% and 23.1%; no statistically
significant difference was detected regarding the presence of
cagA and vacA between 2 groups - resistant and sensitive to
metronidazole (P>0.05).
3.3. Outcomes of several treatment regimens for PDU caused
by drug-resistant H. pylori

3.3.1. Characteristics of patient groups
Total 195 pediatric patients with average age of 7.16 ± 2.41
were eligible and enrolled in the research on using two different
treatment regimens, concretely antimicrobial susceptibility based
regimen (98 patients) and 4 drug regimen (97 patients).
3.3.2. Outcomes of 4 drug regimen

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