Clarithromycin-Resistant Genotypes and Eradication of Helicobacter pylori

17 January 2006 | Volume 144 Issue 2 | Pages 94-100

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.

Editors' Notes Context Point mutations in the peptidyltransferase region of the 23S ribosomal RNA gene may be responsible for Helicobacter pylori clarithromycin resistance. Contribution This study related mutations to eradication rates in 156 adults treated with clarithromycin regimens for H. pylori infection. Eradication was successful in 14 of 15 patients with either A2142G or A2142C point mutations but in only 11 of 23 patients with the A2143G point mutation. Cautions This was a post hoc subgroup study of selected participants in a multicenter randomized trial. Implications The A2143G point mutation may be associated with a low eradication rate of H. pylori infection. —The Editors

 

Author and Article Information

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.

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.