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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey
Bruno Squarcio Sanches, Gustavo Miranda Martins, Karine Lima, Bianca Cota, Luciana Dias Moretzsohn, Laercio Tenorio Ribeiro, Helenice P Breyer, Ismael Maguilnik, Aline Bessa Maia, Joffre Rezende-Filho, Ana Carolina Meira, Henrique Pinto, Edson Alves, Ramiro Mascarenhas, Raissa Passos, Julia Duarte de Souza, Osmar Reni Trindade, Luiz Gonzaga Coelho
Bruno Squarcio Sanches, Gustavo Miranda Martins, Karine Lima, Bianca Cota, Luciana Dias Moretzsohn, Ana Carolina Meira, Henrique Pinto, Edson Alves, Raissa Passos, Julia Duarte de Souza, Osmar Reni Trindade, Luiz Gonzaga Coelho, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil
Laercio Tenorio Ribeiro, Unigastro e Clínica Santa Fé, Maceió, Alagoas 57055-230, Brazil
Helenice P Breyer, Ismael Maguilnik, Hospital de Clínicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Aline Bessa Maia, Fundação Hospital Adriano Jorge, Manaus 69065-001, Brazil
Joffre Rezende-Filho, Hospital das Clínicas, Universidade Federal de Goiás, Goiânia 74605-020, Brazil
Ramiro Mascarenhas, Hospital Geral Roberto Santos, Salvador 41180-780, Brazil
Author contributions: Sanches BS and Coelho LG contributed to the conception and design of the study; Martins GM, Moretzsohn LD, Ribeiro LT, Breyer HP, Maguilnik I, Maia AB, Rezende-Filho J, Meira AC, Pinto H, Alves E, Mascarenhas R and Trindade OR contributed to the collection of biopsies; Sanches BS, Lima K, Cota B and Passos R performed the DNA extraction; Lima K performed the DNA amplification; Cota B and de Souza JD performed the reverse hybridization; Sanches BS interpreted and analyzed the data; Sanches BS and Coelho LG wrote the paper.
Supported by Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais, Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.
Institutional review board statement: This study was approved by the Human Research Ethical Committee of the Federal University of Minas Gerais and the Ethical Committees of the other centers (Protocol in Brazil Platform nº 05004712.0.1001.5149), Brazil.
Informed consent statement: All the treatment procedures were performed after obtaining written informed consent from the patients.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: No additional data are avaliable.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Luiz Gonzaga Coelho, PhD, Professor of Medicine, Department of Internal Medicine, Head of Alfa Institute of Gastroenterology, School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil.
lcoelho22@gmail.com
Telephone: +55-31-32224641 Fax: +55-31-32262886
Received: May 15, 2016
Peer-review started: May 17, 2016
First decision: June 20, 2016
Revised: June 28, 2016
Accepted: July 6, 2016
Article in press: July 6, 2016
Published online: September 7, 2016
Processing time: 112 Days and 10.6 Hours
AIM
To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.
METHODS
The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization.
RESULTS
Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test.
CONCLUSION
The H. pylori clarithromycin resistance rate in Brazil is at the borderline (15%-20%) for applying the standard triple therapy. The fluoroquinolone resistance rate (13.5%) is equally concerning.
Core tip: Antibiotic resistance is the main cause of failure in the treatment of Helicobacter pylori (H. pylori) infection. Using molecular methods, this study investigated bacterial resistance to clarithromycin and fluoroquinolones in 490 adult patients recruited from five regions in Brazil. These patients had never been previously treated for H. pylori infection. Clarithromycin and fluoroquinolone resistance was found in 16.9% and 13.5% of patients, respectively. Resistance to both drugs was found in 4.3% of patients. The mean primary H. pylori clarithromycin resistance rate in Brazil is at the borderline for applying the standard triple therapy, and the primary fluoroquinolone resistance rate is concerning.
