Clarithromycin-Resistant Genotypes and Eradication of Helicobacter pylori

  1. Vincenzo De Francesco, MD;
  2. Marcella Margiotta, BSc;
  3. Angelo Zullo, MD;
  4. Cesare Hassan, MD;
  5. Laura Troiani, MD;
  6. Osvaldo Burattini, MD;
  7. Francesca Stella, MD;
  8. Alfredo Di Leo, MD;
  9. Francesco Russo, MD;
  10. Stefania Marangi, MD;
  11. Rosa Monno, MD;
  12. Vincenzo Stoppino, MD;
  13. Sergio Morini, MD;
  14. Carmine Panella, MD; and
  15. Enzo Ierardi, MD
  1. From Ospedali Riuniti and University of Foggia, Foggia, Italy; University of Bari, Bari, Italy; Ospedale Nuovo Regina Margherita and “San Giacomo” Hospital, Rome, Italy; and IRCSS De Bellis, Castellana Grotte, Italy.

    Abstract

    Background: Three point mutations (A2143G, A2142G, and A2142C) have been involved in Helicobacter pylori clarithromycin resistance.

    Objective: To compare the eradication rates among the different point mutations and the efficacy of triple therapy and a sequential regimen according to genotypic resistance.

    Design: Post hoc subgroup study from a multicenter, randomized trial.

    Setting: Two hospitals in central and southern Italy between January and December 2001.

    Patients: 156 patients with H. pylori infection.

    Measurements: Real-time polymerase chain reaction for assessing clarithromycin resistance; histology, rapid urease test, and 13C-urea breath test at entry and after 4 to 6 weeks.

    Intervention: 7-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 1 g of amoxicillin) in 75 patients or a 10-day sequential regimen (20 mg of rabeprazole plus 1 g of amoxicillin for 5 days and 20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole for the remaining 5 days) in 81 patients. All drugs were given twice daily.

    Results: Helicobacter pylori infection was eradicated in 11 of 23 patients (48%) with the A2143G mutation and in 14 of 15 patients (93%) with either A2142G or A2142C strains (difference, 45 percentage points [95% CI, 15 to 65 percentage points]; P = 0.004). The sequential regimen achieved a higher cure rate than triple therapy in A2143G mutate strains (difference, 49 percentage points [CI, 8 to 72 percentage points]; P = 0.024).

    Limitations: The post hoc substudy design may require further confirmation. Other limitations are the accessibility to the tool and the cost of investigations (€70 per patient).

    Conclusions: The A2143G mutation seemed to be associated with a very low eradication rate. The sequential regimen achieved a higher cure rate than standard therapy even in patients with these strains.

    Article and Author Information

    • Grant Support: The University of Foggia provided funding for reagents, and the University of Bari provided the instruments for the real-time PCR analysis.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Enzo Ierardi, MD, Section of Gastroenterology, Department of Medical Sciences, University of Foggia, Ospedali Riuniti, Viale L. Pinto, 71100 Foggia, Italy; e-mail, e.ierardi{at}virgilio.it.

    • Current Author Addresses: Drs. De Francesco and Stoppino: Gastroenterology Unit, Ospedali Riuniti, Viale L. Pinto, 71100 Foggia, Italy.

    • Ms. Margiotta and Drs. Troiani, Burattini, Di Leo, and Marangi: Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Viale L. Ennio, 70124 Bari, Italy.

    • Drs. Zullo, Hassan, Stella, and Morini: Gastroenterology and Digestive Endoscopy Unit, Ospedale Nuovo Regina Margherita, Via Morosini, 00165 Rome, Italy.

    • Dr. Russo: Biochemistry Laboratory, IRCSS De Bellis, Viale L. Resistenza, 70100 Castellana Grotte, Italy.

    • Dr. Monno: Section of Hygiene, Department of Public Health, University of Bari, Viale L. Ennio, 70124 Bari, Italy.

    • Drs. Panella and Ierardi: Section of Gastroenterology, Department of Medical Sciences, Ospedali Riuniti, Viale L. Pinto, 71100 Foggia, Italy.

    • Author Contributions: Conception and design: V. De Francesco, A. Zullo, C. Hassan, E. Ierardi.

    • Analysis and interpretation of the data: V. De Francesco, A. Zullo, E. Ierardi.

    • Drafting of the article: V. De Francesco, M. Margiotta, A. Zullo, C. Hassan.

    • Critical revision of the article for important intellectual content: C. Hassan, E. Ierardi.

    • Final approval of the article: A. Di Leo, R. Monno, V. Stoppino, S. Morini, C. Panella, E. Ierardi.

    • Provision of study materials or patients: M. Margiotta, R. Monno.

    • Statistical expertise: V. De Francesco, A. Zullo.

    • Obtaining of funding: A. Di Leo.

    • Administrative, technical, or logistic support: M. Margiotta, L. Troiani, O. Burattini, F. Stella, F. Russo, S. Marangi, R. Monno.

    • Collection and assembly of data: M. Margiotta, C. Hassan, L. Troiani, O. Burattini, F. Stella, F. Russo, S. Marangi.

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