Best Treatment Options for Severe Helicobacter pyloriInfections

Best Treatment Options for Severe Helicobacter pyloriInfections

Best Treatment Options for Severe Helicobacter pyloriInfections

Gulhan Kanat Unler1, Ozgur Hilal Erinanc2, Aydın Karakoca3, Huseyin Savas Gokturk1

 

1Department of Gastroenterology, Başkent University Faculty of Medicine, Konya, Türkiye

2Department of Pathology, Baskent University Faculty of Medicine, Konya, Türkiye

3Department of Statistics, Necmettin Erbakan University Faculty of Science, Konya, Türkiye

 

 

Cite this article as: Unler GK, Hilal Erinanc O, Karakoca A, Savas Gokturk H. Best treatment options for severe helicobacter pyloriinfections. Turk J Gastroenterol. 2025;36(12):807-812.

 

ABSTRACT: Background/Aims Helicobacter pylori (H. pylori) affects half of the world’s population. Increasing antibiotic resistance seems to be caus-ing significant clinical problems. The efficacy of bismuth-containing sequential therapy with clarithromycin (BSTC), bismuth-containing sequential  therapy  with  levofloxacin  (BSTL),  and  bismuth-containing  quadruple  therapy  (BQT)  regimens  on  H.  pylori  eradication  was  investigated. The authors also investigated whether high gastric H. pylori colonization density affected treatment success through dif-ferent treatment regimens.

Materials  and  Methods:  A  total  of  751  H.  pylori–positive  patients  were  included  retrospectively  in  the  following  treatment  groups:  sequential therapy with clarithromycin, sequential therapy with levofloxacin, and bismuth-containing quadruple therapy.

Results: There was a significant difference between the 3 treatment protocols in terms of treatment success rates. When the success rates of the applied treatments were examined, the highest success rate was BSTL (85.3%), which was statistically significantly higher than BQT (74.8%) and BSTC (74.8%). A significant difference was found between the success rates of the protocols applied in the group with high bacterial density (P = .003). The success rates in this group were calculated as BSTL (88.6%), BQT (71.4%), and BSTC (79.4%).

Conclusion: It was concluded that BSTL may be the best option for treating H. pylori infections in first-line treatment. This regimen is particularly effective in cases of severe H. pylori colonization.

Keywords: H. pylori, eradication regimens, severe colonization.

 

INTRODUCTION

Helicobacter  pylori  (H.  pylori)  is  a  Gram-negative  bacte-rium  that  affects  nearly  half  of  the  world’s  population.1Helicobacter pylori infection causes gastritis, peptic ulcer disease,  mucosa-associated  lymphoid  tissue  lymphoma,  and gastric cancer. It also plays a role in the development of several systemic diseases, including idiopathic throm-bocytopenia and iron deficiency anemia.2-4The  prevalence  of  H.  pylori  is  10%-50%  in  developed  countries   and   80%   in   developing   countries.1   In   the   TURHEP study, a population cross-sectional study on the prevalence of H. pylori infection in Türkiye, the prevalence of H. pylori in Türkiye was 82.5%.5 This high prevalence of H. pylori and the burden of associated diseases have made its  eradication  a  challenging  issue.  6  Guidelines  for  the  treatment of H. pylori recommend first-line treatment for patients in areas with high clarithromycin resistance with bismuth quadruple therapy for 10-14 days or concurrent quadruple   therapy   without   bismuth.  Clarithromycin-containing  triple  therapy  is  recommended  only  in  areas  with  low  clarithromycin  resistance  and  only  in  patients  who have not received macrolide antibiotics.6-8It  is  important  to  understand  that  H.  pylori  eradica-tion  rates  vary  among  countries,  mostly  due  to  differ-ences  in  antibiotic  resistance.  Therefore,  each  country/region should review its own therapeutic results and the effectiveness of various eradication regimens in H. pylori treatment.9Treatments given in the clinic in 2013 in 621 patients  with  H.  pylori  achieved  eradication  rates  using  intention to treat (ITT) and per-protocol (PP) analysis by treatment groups of 74.6% and 75.6% in classic quadruple treatment,  70.2%  and  70.4%  in  sequential  therapy  with  clarithromycin,  88.5%  and  90.3%  in  bismuth-enhanced  sequential  therapy  (ST)  with  clarithromycin,  77.9%  and  78.5% in sequential therapy with levofloxacin, and 76.1% and 76.2% in hybrid treatment. In  the  present  study,  the  efficacy  of  bismuth-contain-ing  ST  with  clarithromycin  (BSTC),  bismuth-containing  ST   with   levofloxacin   (BSTL),   and   bismuth-containing   quadruple  therapy  (BQT)  regimens  on  H.  pylori  eradica-tion 10 years later was investigated. The authors investi-gated  whether  high  gastric  H.  pylori  colonization  density  affected treatment success through different treatment regimens.

 

MATERIALS AND METHODS

Ethical   approval   for   this   single-center   retrospective   study   was   received   from   Başkent   University   Ethics   Committee      (E-9460333604.01-407243/September      12,  2024).  Gastroscopy  examinations  of  patients  who  presented   to   the   clinic   with   dyspeptic   symptoms   between  January  2022  and  August  2024  were  evalu-ated  retrospectively.  Eight  hundred  seventy  patients  who  were  detected  as  having  H.  pylori  from  pathol-ogy  reports  and  received  eradication  treatment  were  included in the study. Histopathologic analysis of endo-scopic  biopsy  specimens  was  used  to  identify  H.  pyloriinfection status. H. pylori density in biopsies taken from the antrum and corpus was evaluated according to the Sydney  classification  by  a  single  experienced  patholo-gist.  The  density  of  H.  pylori  colonization  was  graded  as  mild,  moderate,  or  severe  according  to  the  Sydney  classification.11If  there  was  a  difference  between  the  2  specimens  in  terms  of  density,  the  highest  grade  was  selected.A   total   of   119   patients   who   had   prior   unsuccessful   empirical H.  pylori  eradication  therapy,  were  aged  under  18  years,  had  allergies  to  antibiotics  (amoxicillin,  metro-nidazole,  clarithromycin,  levofloxacin),  were  on  proton  pump  inhibitors  (PPIs)  or  H2  antagonists  within  the  last  2 weeks, were on bismuth or antibiotics (amoxicillin, met-ronidazole, clarithromycin) within the last month, or who had missing medical information (insufficient data about the treatment protocol) were excluded.

 

Main Points

·         Increasing   antibiotic   resistance   and   the   decrease   in   Helicobacter  pylori  (H.  pylori)  eradication  targets  are  sig-nificant clinical problems.

·         A bismuth-containing sequential therapy with a levofloxa-cin regimen may be preferred for the first-line treatment of H. pylori infection.

·         Bismuth-containing sequential therapy with a levofloxacin regimen is particularly effective in cases of severe H. pyloricolonization.

 

 

Patients  were  given  detailed  explanations  of  the  use  of  the  medications  and  informed  about  possible  adverse  effects.  They  were  also  given  written  information  about  medication  use  and  a  physician’s  phone  number.  Proton  pump   inhibitors   were   prescribed   20   minutes   before   meals, and antibiotics and bismuth were prescribed after meals.There  were  BSTC,  BSTL,  and  BQT  regimens  for  H.  pylorieradication.  Seven  hundred  fifty-one  patients  consti-tuted  the  3  different  groups,  as  given  in  Table  1.  Six  weeks  after  treatment  ended,  repeat  endoscopies  were  performed and graded according to the Sydney score as before.  Patients  were  grouped  based  on  successful  or  failed treatment.Demographic  characteristics  were  compared  between  the  2  groups  using  the  Chi-square  test.  Continuous  and  categorical  variables  were  analyzed  using  the  Bonferroni  test.  A  P-value  less  than  .05  was  considered  statistically  significant.

 

RESULTS

A  total  of  751  patients  were  included  in  the  study;  728  patients were included in the final analysis because 23 did not complete the treatment.It  was  found  that  the  mean  ages  did  not  differ  between  the treatment protocols and that the treatment protocols.

Table 1. Treatment Groups

Group

Treatment Protocol

Group 1 (BQT)

Bismuth quadruple therapy: 14 days
Tetracycline 500 mg qid
Metronidazole 500 mg qid
Bismuth subsalicylate 265 mg qid
Rabeprazole 20 mg bid

Group 2 (BSTC)

Sequential therapy with clarithromycin and bismuth:
First 7 days:
Amoxicillin 1000 mg bid
Rabeprazole 20 mg bid
Bismuth subsalicylate 265 mg qid
Second 7 days:
Clarithromycin 500 mg bid
Metronidazole 500 mg bid
Rabeprazole 20 mg bid
Bismuth subsalicylate 265 mg qid

Group 3 (BSTL)

Sequential therapy with levofloxacin and bismuth:
First 7 days:
Amoxicillin 1000 mg bid
Rabeprazole 20 mg bid
Bismuth subsalicylate 265 mg qid
Second 7 days:
Levofloxacin 500 mg bid
Rabeprazole 20 mg bid
Bismuth subsalicylate 265 mg qid

BQT, bismuth-containing quadruple therapy; BSTC, bismuth-containing sequential therapy with clarithromycin; BSTL, bismuth-containing sequential therapy with levofloxacin.

were homogeneous in terms of age (P = .959). The mean age of the patients was 46.49 ± 0.72 (range, 18-75) years. Of  the  total  751  patients,  425  were  female  (56.5%)  and  326  were  male  (43.5%).  When  the  homogeneity  of  the  treatment groups in terms of sex was tested, it was found that each treatment group was homogeneous (P = .092).Analyses  performed  are  given  for  the  PP  (per-protocol)  treatment completed group. Intention to treat results was not  sufficient  to  draw  a  meaningful  conclusion  because  the number of patients who did not complete the treat-ment was very small (n = 23). In the treatment groups, 8 patients in the BQT treatment group, 9 in the BSTL group, and 6 patients in the BSTC group could not complete the treatment  due  to  adverse  effects.  No  statistical  signifi-cance was found between the groups in terms of adverse effect  frequency  (P  =  .601).  The  most  common  adverse  effects were diarrhea (n = 10), nausea and vomiting (n = 5), bitter taste in the mouth (n = 3), skin rash (n = 3), and dizziness (n = 2).

There  was  a  significant  difference  between  the  3  treat-ment  protocols  in  terms  of  treatment  success  rates  (P=  .003).  When  the  success  rates  of  the  applied  treat-ments were examined, the highest success rate was BSTL (85.3%),  which  was  statistically  significantly  higher  than  BQT  (74.8%)  and  BSTC  (74.8%).  Eradication  rates  of  treatment regimens are given in Table 2.When the success rates of the applied treatment proto-cols were examined, it was observed that BSTL treatment success  rates  showed  a  significant  difference  according  to  sex  (P  =  .015).  BSTL  had  a  success  rate  of  81.3%  in  women  and  91.5%  in  men,  significantly  higher  for  men  than  women.  It  was  observed  that  the  success  rates  of  BQT (P = .931) showed no significant difference accord-ing to sex, 75% in women and 74.5% in men. BSTC (P = .752)  showed  no  significant  difference  according  to  sex  with success rates of 73.8% in women and 75.7% in men.

Table 2. Eradication Rates of Treatment Regimens

Treatment Regimen

Successful Eradication (n)

Total (n)

Eradication Rate (%)

BSTC

157

210

74.80

BQT

163

218

74.80

BSTL

256

300

85.30

BQT, bismuth-containing quadruple therapy; BSTC, bismuth-containing sequential therapy with clarithromycin; BSTL, bismuth-containing sequential therapy with levofloxacin.

 

When the success rates of the applied treatment proto-cols  were  examined  to  see  if  they  differed  according  to  the endoscopy results, it was found that BSTL (P = .885), BQT (P = .966), and BSTC (P = .286) did not differ accord-ing to the endoscopy results.The  authors  examined  whether  the  success  rates  of  the  treatment  protocols  applied  according  to  the  bacterial  density  were  different.  No  statistically  significant  differ-ence was found between the treatment protocols applied in the group with low bacterial density (P = .582). A signif-icant difference was found between the success rates of the protocols applied in the group with medium bacterial density  (P  =  .022).  In  this  group,  the  success  rates  were  calculated  as  BSTL  (84.9%),  BQT  (72.7%),  and  BSTC  (66.2%). A significant difference was found between the success  rates  of  the  protocols  applied  in  the  group  with  high bacterial density (P = .003). The success rates in this group  were  calculated  as  BSTL  (88.6%),  BQT  (71.4%),  and BSTC (79.4%). Eradication rates of regimens accord-ing to H. pylori density are given in Table 3.DISCUSSIONThe   increasing   prevalence   of   antibiotic   resistance   to   agents  used  in  H. pylori  treatment  complicates  manag-ing the infection.6The European H. pylori study suggested that  treatment  regimens  should  achieve  an  eradication  rate  over  80%  on  ITT  analysis  and  85%  on  PP  analy-sis  to  be  acceptable  as  first-line  therapy  for  H.  pylorieradication.12In   general,   eradication   rates   with   these   treatment  protocols  are  low  in  the  country.  Eradication rates   of   bismuth-containing   quadruple   regimens   in   Türkiye  vary  between  77%  and  96.4%,  sequential  treat-ments  (ST)  vary  between  39%  and  82%,  and  levofloxa-cin  containing  treatments,  the  eradication  rates  ranging  from  82%  to  95%.13  According  to  more  recent  stud-ies,  the  eradication  rates  for  concurrent  therapy  and  ST  were greater initially but dropped to 80% in the following years.14-17In Türkiye, eradication rates of the BQT regimen were  81.1%  in  the  study  by  Gokcan  et  al18  and  82.3%  in  the study by Uygun et al.

Table 3. Eradication Rates of Regimens According to Helicobacter pylori Density

H. pylori Intensity

Treatment Regimen

Successful Eradication (n)

Total (n)

Eradication Rate (%)

Low

BSTL

43

56

76.8

 

BQT

39

46

84.3

 

BSTC

25

32

78.1

Intermediate

BSTL

73

86

84.9

 

BQT

64

88

72.7

 

BSTC

47

71

66.2

High

BSTL

140

158

88.6

 

BQT

60

84

71.4

 

BSTC

157

210

74.8

BQT, bismuth-containing quadruple therapy; BSTC, bismuth-containing sequential therapy with clarithromycin; BSTL, bismuth-containing sequential therapy with levofloxacin.

In  the  present  study,  bismuth-based  quadruple  therapy,  and  levofloxacin  and  clarithromycin  STs  were  compared  as first-line treatment for H. pylori eradication. Bismuth-containing  sequential  therapy  with  levofloxacin  had  the  highest eradication rate for H. pylori (P = .003). In addition, the density of H. pylori colonization was related to eradi-cation  success;  the  H.  pylori  eradication  rate  decreased  as  the  density  of  H.  pylori  colonization  increased  in  BQT  and   BSTC   treatments.   Bismuth-containing   sequential   therapy with levofloxacin treatment was also effective in high H. pylori density. In sequential protocols, amoxicillin is  administered  before  other  antibiotics.  Amoxicillin  dis-rupts the bacterial cell wall of H. pylori and allows the anti-biotics administered later to penetrate the bacteria. Due to  the  disrupted  cell  wall,  H.  pylori  cannot  form  a  reflux  pump, and the effect of antibiotics can be preserved.20According  to  a  2023  study  in  Türkiye,  the  overall  resis-tance  rates  were  as  follows:  clarithromycin  28.5%;  met-ronidazole  44.8%;  levofloxacin  23.1%.21  In  the  present  study, the BQT regimen, which also included bismuth, did not show a favorable increase in eradication rates, but the eradication rate of BSLT was highly acceptable. Although the  BQT  results  are  in  parallel  with  these  studies,  it  was  thought that metronidazole resistance might be respon-sible for the lower eradication rates in the BQT regimen.Bismuth exerts a direct bactericidal effect on H.pylori.21-22It is a well-known cytoprotective agent and, by increas-ing   the   Prostaglandin   E2   (PGE2)   level,   it   effectively   protects  gastric  mucosa  against  pepsin.  It  also  exerts  a  synergistic  effect  with  antibiotics  and  may  reduce  the  development of antibiotic resistance.22 Bismuth was also used  in  all  3  regimens  used  in  the  country  due  to  treat-ment resistance.Some  studies  have  reported  that  increased  H.  pyloricolonization density is associated with peptic ulcer forma-tion  and  its  complications.23  Moshkowitz  et  al24reported that  favorable  eradication  rates  were  only  achieved  in patients with low pretreatment urease activity as assessed using urea breath tests (UBTs). In other studies, Lai et al25and  Shah  et  al26  investigated  the  relationship  between  histopathologic pretreatment H. pylori density and bacte-rial eradication and ulcer healing rates. They found a neg-ative  correlation  between  density  and  eradication  rates,  consistent with the results. All these results may suggest that more effective treatment options should be selected in  patients  with  severe  H.  pylori  colonization  density.  In  the past study, it was also found that high bacterial loads in  UBTs  were  negatively  associated  with  the  achieve-ment  of  eradication  with  triple  treatment.  However,  dif-ferences between groups were not significant in patients who received a quadruple eradication regimen in 2016.27In the present study, it was observed that histopathologi-cally, increased H. pylori density had a negative effect on treatment success in all 3 groups.Studies  on  the  CYP2C19  polymorphism  in  Türkiye  have  shown  that  the  percentage  of  “poor”  metabolizers  is  1%-5%,  and  the  percentage  of  “homozygous  exten-sive” metabolizers is 75%-84%.28 In addition, due to the high  rate  of  extensive  metabolizers,  it  is  suggested  that  esomeprazole  and  rabeprazole  should  be  the  preferred  PPIs in Europe and North America.29 Rabeprazole was pre-ferred  in  all  groups  of  the  study.  In  addition,  vonoprazan  is a new proton pump inhibitor that provides a sustained acid inhibitory effect and is approved for the treatment of gastroesophageal reflux disease, suggesting that increas-ing  the  pH  levels  in  the  stomach  using  vonoprazan  may  achieve an optimum eradication rate.30Bismuth-containing sequential therapy with levofloxacin had a success rate of 81.3% in women and 91.5% in men, significantly  higher  for  men  than  for  women  (P  =  .015).  In  other  treatments,  the  results  did  not  change  accord-ing to gender. In this retrospective study, no demographic data that could explain this situation could be found. No publications on this topic in the literature were found. In prospective studies, treatment success could be re-eval-uated based on gender.This   study   had   some   strengths   and   weaknesses.   Its   strengths are that it had a significant number of patients from  a  single  center  and  that  H.  pylori  detection  and  post-treatment follow-up were investigated histopatho-logically.  The  main  limitation  of  this  study  was  its  retro-spective  nature.  Moreover,  no  antibiotic  resistance  was  investigated in this study.A   bismuth-containing   ST   with   levofloxacin   regimen   may  be  preferred  for  the  first-line  treatment  of  H.  Pylori infection.  This  regimen  is  particularly  effective  in  cases  of  moderate  and  severe  H.  pylori  colonization.  Effective  H.  pylori  eradication  could  prevent  severe  complications  associated with this infection and potentially reduce the risk of gastric cancer. Future studies should focus on the long-term effects of these treatments and the potential development of antibiotic resistance.

Data Availability Statement: The data that support the findings of this study are available on request from the corresponding author.

Ethics Committee Approval: This study was approved by the Ethics Committee   of   Başkent   University   (approval   number:   E-94603   33604.01-407243/, date: September 12, 2024).

Informed Consent: N/A.Peer-review: Externally peer-reviewed.

Author    Contributions:    Concept    –    G.K.U.;    Design    –    G.K.U.;    Supervision  –  H.S.G.;  Resources  –  G.K.U.,  O.H.İ.;  Materials  –  G.K.U.;  Data  Collection  and/or  Processing  –  G.K.U.,  O.H.İ.;  Analysis  and/or  Interpretation  –  A.K.;  Literature  Search  –  G.K.U.,  O.H.E.;  Writing  –  G.K.U., O.H.İ.; Critical Review – H.S.G.

Declaration  of  Interests:  Hüseyin  Savaş  Göktürk  is  an  Associate  Editor  at  the  Turkish  Journal  of  Gastroenterology;  however,  his  involvement  in  the  peer  review  process  was  solely  as  an  author.  Other authors have no conflicts on interest.

Funding: This study received no funding.

REFERENCES

1.    Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenter-ology. 2017;153(2):420-429. [CrossRef]

2.    Malfertheiner P, Camargo MC, El-Omar E, et al. Helicobacter pylori infection. Nat Rev Dis Primers. 2023;9(1):19. [CrossRef]

3.    Chiang  TH,  Chang  WJ,  Chen  SLS,  et  al.  Mass  eradication  of  Heli-cobacter  pylori  to  reduce  gastric  cancer  incidence  and  mortality:  a  long-term cohort study on Matsu Islands. Gut. 2021;70(2):243-250. [CrossRef]

4.    Gong  EJ,  Ahn  JY,  Jung  HY,  et  al.  Helicobacter  pylori  Eradication  Therapy  Is  Effective  as  the  Initial  Treatment  for  Patients  with  H.  pylori-Negative and Disseminated Gastric Mucosa-Associated Lym-phoid Tissue Lymphoma Gut and Liver; vol 10(5); 2016:706-713.

5.    Ozaydin  N,  Turkyilmaz  SA,  Cali  S.  Helicobacter  pylori  in  Turkey:  a  nationally-representative,    cross-sectional,    screening    with    the    13C-Urea  breath  testPrevalence  and  risk  factors  of.  BMC  Public  Health. 2013;13:1215. [CrossRef]

6.    Malfertheiner P, Megraud F, Rokkas T, et al. Management of Heli-cobacter   pylori   infection:   the   MaastrichtVI/Florence   consensus   report. Gut. 2022:gutjnl-2022-327745. [CrossRef]

7.    Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the treatment of Helicobacter pylori infection in adults. Gastro-enterology. 2016;151(1):51-69.e14. [CrossRef]

8.    Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guide-line: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212-239. [CrossRef]

9.    Peleteiro B, Bastos A, Ferro A, Lunet N. Helicobacter pylori infection worldwide:  a  systematic  review  of  studies  with  national  coverage-Prevalence of. Dig Dis Sci. 2014;59(8):1698-1709. [CrossRef]

10. Unler GK, Ozgur GT, Gokturk HS, Karakoca A, Erinanc OH. A com-parison  of  five  different  treatment  regimens  as  the  first-line  treat-ment  of  Helicobacter  pylori  in  Turkey.  Helicobacter.  2016;21(4):  279-285. [CrossRef]

11.  Dixon  MF,  Genta  RM,  Yardley  JH,  Correa  P.  Classification  and  grading  of  gastritis.  The  updated  Sydney  System.  International  Workshop  on  the  Histopathology  of  Gastritis,  Houston  1994.  Am  J  Surg Pathol. 1996;20(10):1161-1181. [CrossRef]

12. Graham DY, Lu H, Yamaoka Y. A report card to grade Helicobac-ter pylori therapy. Helicobacter. 2007;12(4):275-278. [CrossRef]

13.  Kaplan  M,  Tanoglu  A,  Duzenli  T,  Tozun  AN.  Helicobacter  pylori  treatment in Turkey: current status and rational treatment options. North Clin Istanb. 2020;7(1):87-94. [CrossRef]

14. Erdoğan FA, Abacı K, Serin E, Özer B, İçer MO. Helicobacter pylori eradication  therapies  alarming?Are  first-line  Akademik  Gastroen-teroloji Dergisi 2009;8:59-62.

15.  Aydın  Y,  Nazlıgül  Y,  Yeniova  AÖ,  et  al.  Helicobacter  pylori  eradi-cationThe efficacy of levofloxacin based triple therapy for first-line. Dicle Med J. 2011;38:197-201.

16. Kefeli A, Başyigit S, Yeniova AO, Ozkan S, Nazligul Y. Helicobacter pylori  infection  in  TurkeyComparison  of  the  efficacy  and  safety  of  hybrid and sequential therapies as a first-line regimen for. Arch Med Sci. 2018;14(2):276-280. [CrossRef]

17. Kuloğlu E, Albayrak B, Dursun H, Albayrak F, Yılmaz Ö. Compari-son of sequential, hybrid, and quadruple therapy protocols in Helico-bacter  pylori  eradication:  a  Single-Center  Study.  Eurasian  J  Med.  2022;54(3):235-238. [CrossRef]

18.  Gokcan  H,  Oztas  E,  Onal  IK.  Different  bismuth-based  therapies  for  eradicating  Helicobacter  pylori:  randomized  clinical  trial  of  effi-cacy  and  safety.  Clin  Res  Hepatol  Gastroenterol.  2016;40(1):124-131. [CrossRef]

19.  Kadayifci  A,  Uygun  A,  Polat  Z,  et  al.  Comparison  of  bismuth-containing  quadruple  and  concomitant  therapies  as  a  first-line  treatment   option   for   Helicobacter   pylori.   Turk   J   Gastroenterol.   2012;23(1):8-13. [CrossRef]

20. De Francesco V, Margiotta M, Zullo A, et al. Clarithromycin resist-ant  genotypes  and  eradication  of  Helicobacter  pylori.  Ann  Intern  Med. 2006;144(2):94-100. [CrossRef]

21.   Örsten   S,   Yılmaz   E,   Akyön   Y.   Molecular   characterization   of   clarithromycin resistance in Helicobacter pylori Strains. Turk J Gas-troenterol. 2023;34(4):427-432. [CrossRef]

22. Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication  with  a  capsule  containing  bismuth  subcitrate  potas-sium,  metronidazole,  and  tetracycline  given  with  omeprazole  ver-sus      clarithromycin-based      triple      therapy:      a      randomised,      open-label,non-inferiority,  phase  3  trial.  Lancet.  2011;377(9769):905-913. [CrossRef]

23.  Sheu  BS,  Yang  HB,  Su  IJ,  Shiesh  SC,  Chi  CH,  Lin  XZ.  Bacterial  density  of  Helicobacter  pylori  predicts  the  success  of  triple  therapy  in  bleeding  duodenal  ulcer.  Gastrointest  Endosc.  1996;44(6):683-688. [CrossRef]

24.  Moshkowitz  M,  Konikoff  FM,  Peled  Y,  et  al.  High  Helicobacter  pylori  numbers  are  associated  with  low  eradication  rate  after  triple  therapy. Gut. 1995;36(6):845-847. [CrossRef]

25. Lai YC, Wang TH, Huang SH, et al. Density of Helicobacter pylori may  affect  the  efficacy  of  eradication  therapy  and  ulcer  healing  in  patients   with   active   duodenal   ulcers.   World   J   Gastroenterol.   2003;9(7):1537-1540. [CrossRef]

26.  Shah  DK,  Jain  SS,  Mohite  A,  Amarapurkar  AD,  Contractor  QQ,  Rathi PM. Effect of H. pylori density by histopathology on its compli-cations and eradication therapy. Trop Gastroenterol. 2015;36(2):101-106. [CrossRef]

27. Unler GK, Ozgur GT, Gokturk HS, Durukan E, Erhamamci S. Does the urea breath test predict eradication of Helicobacter pylori infec-tion? Acta Gastroenterol Belg. 2016;79(1):3-7.

28.  Ormeci  A,  Emrence  Z,  Baran  B,  et  al.  Can  Helicobacter  pylori  be  eradicated   with   high-dose   proton   pump   inhibitor   in   extensive   metabolizers  with  the  CYP2C19  genotypic  polymorphism?  Eur  Rev  Med Pharmacol Sci. 2016;20(9):1795-1797.

29. Klotz U. Clinical impact of CYP2C19 polymorphism on the action of  proton  pump  inhibitors:  a  review  of  a  special  problem.  Int  J  Clin  Pharmacol Ther. 2006;44(7):297-302. [CrossRef]

30.  Huang  J,  Lin  Y.  Vonoprazan  on  the  eradication  of  Helicobacter  pylori     infection.     Turk     J     Gastroenterol.     2023;34(3):221-226. [CrossRef]

About Health

Get Appointment