Tratament Helicobacter Pylori

Helicobacter Pylori

 H. pylori colonizeaza mucoasa antrala, fiind deosebit de bine adaptat la conditiile ostile oferite de
stomac.
 Odata stabilit in stomac poate persista o lunga perioada de timp, chiar toata viata.
 Poate disparea spontan odata cu instalarea gastritei atrofice ce determina disparitia receptorilor
specifici.
 Sunt bacterii Gram negative, incurbate sau spiralate, prezentand 4-6 flageli localizati la un
pol.
 La microscopul electronic pot avea forma literei S sau pot fi cocoide. H. pylori produce colonii de
tip S, translucide, de 1-2 mm.
 Sunt bacterii care cresc in conditii de microaerofilie, au metabolism respirator, nu cresc la
25grade C, sunt oxidazo pozitive.
 Principala caracteristica este producerea de ureaza in cantitati mari, descompunand ureea
din mediu in 5-20 de minute.
 Testul ureazei este astfel principalul test screening in diagnostic.
 H. pylori prezinta sase structuri antigenice: ureaza, proteinele de soc termi (HSP B), lipoproteina
20, DnaK, metionin-sulfoxid-reductaza A. (1)

Alternative de tratament
Principii de baza

Inhibitorii de pompă de protoni (IPP). Dozele crescute de IPP (de două ori pe zi) sunt mai
eficiente decât dozele standard pentru eradicarea HP. Studii recente recomandă
administrarea IPP la doze crescute pentru a obține rezultate optime.

 Terapia de prima linie cu claritromicina

a. Concomitant therapy consisting of a PPI, clarithromycin, amoxicillin and a

nitroimidazole for 10–14 days is a recommended first-line treatment option (Strong
recommendation, low quality of evidence (for duration: very low quality of evidence)).
b. Clarithromycin triple therapy consisting of a PPI, clarithromycin, and amoxicillin or
metronidazole for 14 days remains a recommended first-line treatment option in regions
where H. pylori clarithromycin resistance is known to be <15% and in patients with no
previous history of macrolide exposure for any reason (conditional recommendation, low
quality of evidence (for duration: moderate quality of evidence)).
c. Sequential therapy consisting of a PPI and amoxicillin for 5–7 days followed by a PPI,
clarithromycin, and a nitroimidazole for 5–7 days is a suggested first-line treatment
option (conditional recommendation, low quality of evidence (for duration: very low
quality of evidence).
 d. Hybrid therapy consisting of a PPI and amoxicillin for 7 days followed by a PPI,
amoxicillin, clarithromycin and a nitroimidazole for 7 days is a suggested first-line
treatment option (conditional recommendation, low quality of evidence (For duration:
very low quality of evidence)).(2)

e. Reluarea schemei terapeutice este necesară când a fost demonstrat eșecul terapeutic, dar
nu poate fi realizată doar pe baza persistenței simptomatologiei. Eșecul la claritromicină
ca primă linie poate fi, de fapt, expresia  rezistenței primare sau dobândite la
claritromicină; în aceste cazuri, utilizarea claritromicinei în schema terapeutică de a doua
intenție este descurajată.

În ultima decadă, eficacitatea terapiei standard, de 7 zile, bazată pe IPP (IPP + claritromicină +
amoxicilină sau metronidazol) a scăzut la niveluri inacceptabile, din cauza creșterii prevalenței
rezistenței la claritromicină.
Studii recente relevă că tripla terapie timp de 14 zile este mai eficientă decât cea de 7 sau 10 zile,
cu rate globale de eradicare >80%.
Terapia secvențială timp de 10 zile este și mai eficientă, cu rate de eradicare >90% ca primă linie
de tratament.
Prin urmare, ca primă linie de tratament pentru eradicarea HP se recomandă:

 terapia standard bazată pe IPP conținând claritromicină - timp de 14 zile;

 terapia secvențială timp de 10 zile;
 terapia concomitentă timp de 10 zile (dar nu cvadruplă ce conține bismut).

Alegerea terapiei se bazează pe experiența clinică a medicului și pe profilul pacientului.

2. A doua linie de tratament

 Ghidurile europene actuale recomandă ca a doua linie de tratament cvadrupla terapie
conținând bismut sau tripla terapie timp de 10 zile ce conține levofloxacină.
 Tripla terapie IPP + levofloxacină + amoxicilină nu a fost inferioară în ceea ce privește
eficacitatea comparativ cu cvadrupla terapie ce conține bismut, aceasta realizând rate de
succes de 88%.
 Mai mult, incidența efectelor secundare ale triplei terapii cu levofloxacină a fost mai mică
decât la cvadrupla terapie cu bismut.
 Prin urmare, după eșecul terapiei de primă linie se recomandă tripla terapie cu
levofloxacină-amoxicilină timp de 10 zile. Cvadrupla terapie conținând bismut este o
alternativă, dacă aceasta este disponibilă. (3)
 Bismuth quadruple therapy (Terapia cvadrupla) consisting of a PPI, bismuth,
tetracycline, and a nitroimidazole for 10–14 days is a recommended first-line treatment
option. Bismuth quadruple therapy is particularly attractive in patients with any previous
macrolide exposure or who are allergic to penicillin (strong recommendation, low quality
of evidence)

 Utilizarea altor antibiotice. Cefalosporinele, chinolonele altele decât levofloxacina (ex.:

moxifloxacina), unele tetracicline (doxiciclina) nu trebuie utilizate în eradicarea HP, din
cauza eficienței scăzute.

3. A treia linie de tratament

 După eșecul primelor două opțiuni terapeutice, ghidurile europene recomandă cultura HP
și testarea susceptibilității genetice pentru o mai bună alegere a schemei antibacteriene de
rezervă, bazată pe identificarea rezistenței antimicrobiene specifice a tulpinii de HP.
 Este necesară îndrumarea pacientului către o clinică de specialitate unde se realizează
astfel de testări.
  După eșecul celei de a doua linii terapeutice cu triplă terapie timp de 10 zile cu
levofloxacină, se poate utiliza ca a treia linie de tratament cvadrupla terapie cu săruri de
bismut, unde acestea sunt disponibile.
 O altă opțiune terapeutică este cea cu regimuri bazate pe rifabutină, în infecția HP
refractară. Rezistența HP la rifabutină este, în general, foarte scăzută.
 Nivel de evidență: 3a; grad de recomandare: A

4. Tratamentul adjuvant cu probiotice

 În ultima perioadă, utilizarea probioticelor ca terapie adjuvantă în eradicarea HP a fost
studiată.
 Anumite probiotice, ca lactobacili, bifidobacterii și Saccharomyces boulardii, au efect
anti-HP in vitro și sunt utile și în reducerea efectelor secundare terapiilor cu
antibiotice. Studii ulterioare sunt necesare pentru confirmarea efectelor
probioticelor în regimurile terapeutice anti-HP.
 Nivel de evidență: 3a; grad de recomandare: B 

**** O alta varianta de tratament care s-a dezvoltat datorita rezistentei la claritromicina
este cu Azitromicina.

ATENTIE !!!
- dacă sunteţi alergic (hipersensibil) la eritromicină, la orice antibiotic macrolid (ex:
claritromicina) !!! sau ketolid sau la oricare dintre celelalte componente ale Azitromicină
Terapia;
- dacă utilizaţi concomitent alcaloizi din secară cornută (dihidroergotamină, ergotamină).
In asociere cu esomeprazol si amoxicilina sau
-lansoprazol si metronidazol:

Schema de tratament:

1. Azitromicina 1g/zi doza unica, 3 zile.

2. Esomeprazol 20 mg 2cp/zi, 7 zile.
3. Amoxicilina 1 gx2/zi, 7 zile. Sau Metronidazol 500 mg x3/zi (4)

Table 2. Recommended first-line therapies for H pylori infection

Regimen Drugs (doses) Dosing Duration FDA

 frequency (days) approval

Clarithromycin triple PPI (standard or double dose) BID 14 Yesa

  Clarithromycin (500 mg)      

  Amoxicillin (1 grm) or Metronidazole      

(500 mg TID)

Bismuth quadruple PPI (standard dose) BID 10–14 Nob

  Bismuth subcitrate (120–300 mg) or QID    

subsalicylate (300 mg)

  Tetracycline (500 mg) QID    

  Metronidazole (250–500 mg) QID (250)    

    TID to QID    
(500)

Concomitant PPI (standard dose) BID 10–14 No

  Clarithromycin (500 mg)      

  Amoxicillin (1 grm)      

  Nitroimidazole (500 mg)c      

Sequential PPI (standard dose)+Amoxicillin (1 BID 5–7 No
grm)

  PPI, Clarithromycin (500 mg) BID 5–7  

+Nitroimidazole (500 mg)c

Hybrid PPI (standard dose)+Amox (1 grm) BID 7 No

  PPI, Amox, Clarithromycin (500 mg), BID 7  

Nitroimidazole (500 mg)c

Levofloxacin triple PPI (standard dose) BID 10–14 No

  Levofloxacin (500 mg) QD    

  Amox (1 grm) BID    

Levofloxacin PPI (standard or double dose)+Amox BID 5–7 No

sequential (1 grm)

  PPI, Amox, Levofloxacin (500 mg BID 5–7  

QD), Nitroimidazole (500 mg)c

LOAD Levofloxacin (250 mg) QD 7–10 No

  PPI (double dose) QD    

  Nitazoxanide (500 mg) BID    

  Doxycycline (100 mg) QD    

BID, twice daily; FDA, Food and Drug Administration; PPI, proton pump inhibitor; TID, three times daily; QD, once daily;
QID, four times daily.
a
 Several PPI, clarithromycin, and amoxicillin combinations have achieved FDA approval. PPI, clarithromycin and
metronidazole is not an FDA-approved treatment regimen.
b
 PPI, bismuth, tetracycline, and metronidazole prescribed separately is not an FDA-approved treatment regimen.
However, Pylera, a combination product containing bismuth subcitrate, tetracycline, and metronidazole combined with a
PPI for 10 days is an FDA-approved treatment regimen.
c
 Metronidazole or tinidazole.

In cazul de rezistenta la 3 optiuni terapeutice se poate incerca si:

Rifabutin-containing therapy - Rifabutin 150 mg BID

Recomandari

Table 3.Summary of Consensus Recommendations for the Treatment of H pylori Infection all
patients

1. In patients with H pylori infection, we recommend a treatment duration of 14 days. GRADE:

Strong recommendation; quality of evidence moderate for PAC and very low for PBMT,
PAMC, and PAL. First-line therapy
2. 2. In patients with H pylori infection, we recommend that the choice of first-line therapy
consider regional antibiotic resistance patterns and eradication rates. GRADE: Strong
recommendation; quality of evidence low.
3. 3. In patients with H pylori infection, we recommend traditional bismuth quadruple therapy
(PBMT) for 14 days as one of the options for first-line therapy. GRADE: Strong
recommendation; quality of evidence moderate for efficacy and very low for duration.
4. 4. In patients with H pylori infection, we recommend concomitant nonbismuth quadruple
therapy (PAMC) for 14 days as one of the options for first-line therapy. GRADE: Strong
recommendation; quality of evidence moderate for efficacy and very low for duration.
5. 5. In patients with H pylori infection, we recommend restricting the use of PPI triple therapy
(PAC or PMC for 14 days) to areas with known low clarithromycin resistance (85%).
GRADE: Strong recommendation; quality of evidence moderate for efficacy of PPI triple
therapy for 14 days and low for restrictions.
6. 6. In patients with H pylori infection, we recommend against the use of levofloxacin triple
therapy (PAL) as a first-line therapy. GRADE: Strong recommendation; quality of evidence
very low.
7. In patients with H pylori infection, we recommend against the use of sequential nonbismuth
quadruple therapy (PA followed by PMC) as a first-line therapy. GRADE: Strong
recommendation; quality of evidence moderate. Prior failure
8. In patients who have previously failed to respond to H pylori eradication therapy, we
recommend traditional bismuth quadruple therapy (PBMT) for 14 days as an option for
subsequent therapy. GRADE: Strong recommendation; quality of evidence low.
9. In patients who have previously failed to respond to H pylori eradication therapy, we
suggest levofloxacin-containing therapy for 14 days as an option for subsequent therapy.
GRADE: Conditional recommendation; quality of evidence low.
10. In patients who have previously failed to respond a clarithromycin-containing H pylori
eradication therapy, we recommend against the use of clarithromycin-containing regimens as
subsequent therapy. GRADE: Strong recommendation; quality of evidence low.
11. In patients who have previously failed to respond to a levofloxacin-containing H pylori
eradication therapy, we recommend against the use of levofloxacin-containing regimens as
subsequent therapy. GRADE: Strong recommendation; quality of evidence low.
12. In patients who have previously failed to respond to H pylori eradication therapy, we
recommend against the use of sequential nonbismuth quadruple therapy (PA followed by
PMC) as an option for subsequent therapy. GRADE: Strong recommendation; quality of
evidence very low.
13. We recommend restricting the use of rifabutin-containing regimens to cases in which at
least 3 recommended options have failed. GRADE: Strong recommendation; quality of
evidence very low. Supplemental therapy
14. 14. In patients with H pylori infection, we recommend against routinely adding probiotics to
eradication therapy for the purpose of reducing adverse events. GRADE: Strong
recommendation; quality of evidence very low.
15. 15. In patients with H pylori infection, we recommend against adding probiotics to
eradication therapy for the purpose of increasing eradication rates. GRADE: Strong
recommendation; quality of evidence very low. NOTE. The consensus group concluded that
there was insufficient evidence to support or refute the efficacy of PAMC as a second-line
option and thus was unable to recommend for or against this regimen as a rescue therapy.
Similarly, the group concluded that there was insufficient evidence to make a recommendation
on high-dose dual therapy with a PPI and amoxicillin. (5)

Reactii adverse

Common side effects associated with amoxicillin include GI upset, headache, and diarrhea.

Side effects of metronidazole tend to be dose related and include a metallic taste in the mouth,
dyspepsia, and a disulfiram-like reaction with alcohol consumption.

Common side effects of tetracycline include GI upset and photosensitivity. This antibiotic
should not be used in children under 8 yr of age because of possible tooth discoloration.
Finally, bismuth compounds have been associated with darkening of the tongue and stool,
nausea, and GI upset (145). Informed patients are less likely to be alarmed when side effects that
they are aware of occur and, consequently, less likely to needlessly stop their treatment. (6)

Bibliografie

1. https://dictionar.romedic.ro/caractere-helicobacter-pylori
2. http://gi.org/guideline/treatment-of-helicobacter-pylori-infection/
3. https://www.medichub.ro/reviste/pediatru-ro/ghid-de-practica-actuala-in-diagnosticul-si-
tratamentul-infectiei-cu-helicobacter-pylori-id-395-cmsid-64
4. http://www.spitalbuhusi.ro/wp-content/uploads/2015/11/Ghid-de-tratament-in-infectia-cu-
helicobacter-pyloti.pdf
5. https://www.cag-acg.org/images/publications/Hp_Toronto_Consensus_2016.pdf
6. http://s3.gi.org/physicians/guidelines/ManagementofHpylori.pdf