Comment traiter aujourd’hui !

Based on the join ESPGHAN/NASPGHAN

guidelines on the Management of

Helicobacter pylori infection in children

Koletzko et al. JPGN 2011

Tri-thérapie 7j adaptée à la sensibilité des souches

o Arenz et al. JPGN 2006

 54/58 (93%, 95%CI 83-98%) enfants éradiqués (PP = ITT)

 49/53 (92%) avec EAC 7j

 5/5 avec EAM 7j

Tri-thérapie 7j adaptée à la sensibilité des souches vs séquentiel

Bontems et al. JPGN 2011

Traitement séquentiel

Deux périodes successives de 5 jours combinant:

Inhibiteur de la pompe à proton avec de l’Amoxicilline 5j

Suivi trithérapie (IPP, Clarithromycine, Métronidazole) 5j

Meta-analyse (Gatta 2009)

260 enfants et adolescents

3 études randomisées controlées

OR traitement séquentiel vs tri-thérapie 1.98

95% CI 0.96–4.07

sensibilité aux antibiotiques non disponibles

o 2009: Sequential treatment superior to standard triple

therapy in adults but not significantly advantage

 Gatta et al. Am J Gastroenterol

o 2013: Sequential treatment 10d superior to standard triple

therapy 7d but not to STT 10 or 14d

o Horvath et al. APT

o 2015: Sequential treatment 10d superior to standard triple

therapy given 7 or 10 d but not for 14d (number to treat =

16 !)

o Huang et al. 2015

However, eradication rate still less than desired

Meta-analysis in children

Sequential versus triple therapy for H. pylori eradication

in children

• No antimicrobial susceptibility testing in most studies

• Adherence to therapy not assessed

• Small number of patients

• Insufficient eradication rates

Horvath et al. APT 2013

77%72%

Recommendation 12/16

o We recommend that the effectiveness of first-

line therapy be evaluated in national/regional

centers.

 Practice Points:

1. To avoid further investigations, and induction of

secondary resist- ance in the infecting H. pylori strains, a

primary success rate for eradication should be more

than 90% in per-protocol analysis.

2. Improvement care strategy needed locally to obtain the

recommended target of 90% of efficacy.

Jones et al. JPGN 2017

Quality control circle of Deming

Taux d’éradication chez l’enfant

Traitement

(1-2 semaines)

enfant (n)

Eradication PP

(%)

95% CI

Ome-Amo-Clar 175 61 53-68

Ome-Amo-Metro 83 66 55-76

Bis-Amo-Metro 56 80 68-90

Bis-Clar-Metro 45 73 58-85

Lan-Amo-Metro 28 57 37-75

Ome-Clar-Metro 20 95 75-100

(Oderda et al. Helicobacter 2007)

Possibility to improve the eradication rates in children

o Increase the duration of the tailored triple

therapy to 14d

o Double check the dosage prescribed, must be

superior to:

 > 50 mg/kg for AMO

 > 25 mg/kg for CLA

 > 20 mg/kg for MET

 > 1-2 mg/kg for PPI

o Amoxicillin in tid

o Probiotic to prevent side effects

o Use concomitant quadruple therapy

o Statement 10: Extending the duration of PPI-

clarithromycin-containing triple therapies from 7 to

10 or 14 days improves the eradication success by

about 5% and may be considered.

Evidence level: 1a

Malfertheiner et al. Gut 2012

Fuccio et al. Ann Intern Med 2007

Effect of triple therapy duration on efficacy in adults

Fallone et al. Gastroenterology 2016

Tailored triple therapy 7d

Kato et al. J Gastroenterol 2004

Tailored Sequential vs tailored triple therapy 10 days

Kotilea et al. Helicobacter 2016

After adjustment for adherence and adverse events

Morning Evening

Esomeprazol

15-24 kg 20 mg 10 mg

25-34 kg 20 mg 20 mg

> 35 kg 40 mg 20 mg

> 50 kg 40 mg 40 mg

Amoxicillin

15-24 kg 500 mg 500 mg

25-34 kg 750 mg 750 mg

35-49 kg 1000 mg 1000 mg

> 50 kg 1500 mg 1500 mg

Metronidazole

15-24 kg 250 mg 250 mg

25-34 kg 500 mg 250 mg

35-49 kg 500 mg 500 mg

> 50 kg 750 mg 750 mg

Clarithromycin

15-24 kg 250 mg 250 mg

25-34 kg 500 mg 250 mg

35-49 kg 500 mg 500 mg

> 50 kg 500 mg 500 mg

Concomitant quadruple superior to sequential treatment in adults

Fallone et al. Gastroenterology 2016

86%77%

88%82%

Treatments recommended in adults

Fallone et al. Gastroenterology 2016

Recommendation 11/16

o We recommend that antimicrobial sensitivity be

obtained for the infecting H. pylori strain (s), and

eradication therapy tailored accordingly.

 Practice Points:

1. antimicrobial susceptibility testing should be based on

culture or molecular techniques.

2. the transport of biopsies in special transport media will

enhance the success rate for culture.

3. new molecular technique for clarithromycin resistance on

stool samples.

4. to detect colonizing strains with different resistance

patterns, gastric biopsies be obtained from at least 2

different locations (ie, antrum and body). The biopsies can

be sent to the laboratory in the same jar.

Jones et al. JPGN 2017

Effect of H. pylori antibiotic resistance on eradication rates

Randomized trial comparing two 14d triple regimen

Nguyen et al. Helicobacter 2012

Discordant antibiotic susceptibility between antrum and corpus

isolates for different antibiotics was seen in 15.2% (10/66)

Selgrad et al. World J Gastroenterol

Recommendation 13/16

o We recommend that the physician explain to

the patient/family the importance of

adherence to the anti – H. pylori therapy to

enhance successful eradication.

 Practice Points:

1. Patient information leaflets with individualized schedules

for drug intake may improve adherence.

Jones et al. JPGN 2017

Kotilea et al. Helicobacter 2017

TREATMENT OF

HELICOBACTER

PYLORI INFECTION

IN CHILDREN.

INFORMATION

FOR PARENTS

TREATING PHYSICIAN (Stamp)

IMPRESSUM

Developed by the Helicobacter pylori Working Group

on behalf of the European Society of Paediatric Gastroenterology,

Hepatology and Nutrition (ESPGHAN)

Rue De-Candolle 16

1205 Geneva, Switzerland

E-Mail: office@espghan.org

Diary for reporting drug intake, side effects and speical events during

H. pylori

therapy

What is Helicobacter pylori (H. pylori)?

H. pylori is a bacterium that infects the stomach.

H. pylori infection is common in some countries,

mostly acquired during the first five years of life.

Without treatment, it persists in the stomach.

A new infection is less likely to occur after this age.

Most infected children have no symptoms.

Some children may develop symptoms including

abdominal pain, nausea, and vomiting.

Possible consequences

of H. pylori

 All infected children have

some inflammation of the

stomach (gastritis), but in

most affected children this

does not cause symptoms or problems.

 Few infected children develop an ulcer

in the duodenum or stomach.

 Very rarely, malignancy (gastric cancer or

lymphoma) may develop in adulthood.

Figure: H. pylori is hidden below the mucus layer (left).

Occasionally, the infection damages the stomach lining (mucosa)

to cause an erosion or ulcer (right).

How is H. pylori diagnosed?

At initial diagnosis an endoscopy with biopsies

is performed. This allows to see whether an ulcer

is present and to take little tissue samples for

investigations under the microscope (histology), and

to test which antibiotics work best of the bacteria.

Treatment in children should not be based on

a stool test or breath test or blood test.

What is important to know about

H. pylori therapy?

 At least two different antibiotics plus acid

suppressing drugs (proton pump inhibitor, PPI)

are needed.

 Medication must be taken as prescribed

(dose and duration).

Please report each intake in the diary.

 The bacteria live below the mucus layer and

are difficult to reach with drugs (see Figure).

 Only few antibiotics can kill these bacteria.

 Many H. pylori bacteria are resistant against

common antibiotics, so they do not work.

 Before treatment inform your doctor

if your child is allergic to any antibiotic.

It is very important to take all medications

for the whole duration as prescribed

by your doctor to treat the infection successfully!

Adverse effect of the treatment

may occur

 Adverse effects like diarrhoea, abdominal pain or

vomiting are common when taking antibiotics.

 If they are so severe that you need to stop the

medication please contact your doctor.

How do we know that treatment

was successful?

A diagnostic test 6 to 8 weeks after treatment

is necessary to prove successful therapy.

One of the following tests are appropriate:



13

C-urea breath test (UBT)

 stool test

 repeat endoscopy when indicated

These tests are only reliable if antibiotics are stopped

4 weeks and acid suppressing drugs (PPI) at least

2 weeks before testing.

New infections after cure are rare. There is no need

to investigate family members without complaints

in order to avoid re-infection.

If you have further questions please contact

your pediatric gastroenterologist or pediatrician.

Resolution or change of symptoms does not

tell whether the infection is cleared or not

Duodenal ulcer

Inflammation

Medications

(filled by physician)

Total dose

mg/day

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14

PPI: ____________________

Before meal, in 2 doses

With / before meal

Special events Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14

Abdominal pain

Diarrhea (liquid stool)

Vomiting

Metallic taste

Having cold

Having fever

Other: ______________________________

Diary for reporting drug intake, side effects and speical events during H. pylori

therapy

Electronic pills reminder and medication tracker

Recommendation 14/16

o We recommend first-line therapy for H. pylori

infection as listed:

Jones et al. JPGN 2017

H. pylori

antimicrobial susceptibility

Suggested treatment

Known

Susceptible to CLA and to MET

PPI

-AMO-CLA 14d or sequential 10d

Resistant to CLA, susceptible to MET

PPI

-AMO-MET 14d or bismuth-based

Resistant to MET, susceptible to CLA

PPI

-AMO-CLA 14d or bismuth-based

Resistant to CLA and to MET

PPI

-AMO-MET 14d or bismuth-based

Unknown

PPI

-AMO-MET 14d or bismuth-based

Recommendation 15/16

o We recommend that the outcome of anti–H.

pylori therapy be assessed at least 4 weeks after

completion of therapy using one of the

following tests:

a)

13

C-urea breath (

13

C-UBT) test.

b) 2-step monoclonal stool antigen test.

 Practice Points

1. The relief of symptoms is not an indicator for successful

treatment.

2. Endoscopy and biopsy-based tests to confirm

eradication are rarely needed in pediatric patients with

uncomplicated PUD.

3. The use of

14

C-UBT is not recommended in children.

Recommendation 16/16

o We recommend that when H. pylori treatment

fails, rescue therapy should be individualized

considering antibiotic susceptibility, the age of

the child, and available antimicrobial options:

Jones et al. JPGN 2017

o No data concerning the efficacy of

second line eradication treatments

o We assume the efficacy of second-line

treatments are similar to that of first-line

o High number of naïve patients already

treated with a standardized regimen

Conclusions

o Benchmarking (performance)

 Primary success rate must be over 90% in PP

o Antimicrobial susceptibility

 Treatment tailored accordingly

 Clarithromycin should not be used when susceptibility is

unknown

 CLAr about 20%, METr about 30%

o Adherence

 High success rate only achieved when > 90%

 Treatment delayed if clear obstacle to adherence

o Longer duration of treatments