Detection ofHelicobacter pyloriresistance to clarithromycin and fluoroquinolones in Brazil: A national survey

Abstract

AIMTo evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods.METHODSThe 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.RESULTSClarithromycin 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.CONCLUSIONThe 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.

Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

“…The most common point mutation conferring resistance to fluoroquinolones in our patients was gyr91 D91Y. This contrasts with other studies in which gyr91 D91N and gyr87 N87K mutations were reported with highest frequency[ 14 , 16 - 18 ].…”

The interplay between mutations in cagA, 23S rRNA, gyrA and drug resistance in Helicobacter pylori

“…The mutations were detected at positions Asn87 83.3% (15/18) and Asp91 16.7% (3/18) in gyrA. The presence of mutations in these regions also has been previously reported in several countries, including Brazil 3 , 8 , 15 .…”

H. pylori

“…Este aumento verificou-se na maior parte da Europa, atingindo atualmente uma prevalência maior que 20%, considerada uma taxa de resistência elevada na maioria dos países da Europa central, ocidental e do sul da Europa 11 . Este resultado complementa as informações obtidas com um estudo realizado no Brasil envolvendo diferentes regiões para a determinação molecular da resistência genotípica primária de H. pylori à claritomicina e fluorquinolonas, que detectou resistência à claritromicina e a fluoroquinolona em pacientes 12 .…”

“…Outra pesquisa, realizada na Palestina para sensibilidade do H. pylori a seis antibióticos, a ciprofloxacina foi a droga mais eficaz contra o patógeno (0% de resistência), seguida pela levofloxacina (0%), moxifloxacina (3%) e amoxicilina (18%). O metronidazol e a claritromicina foram os menos eficazes, com taxas de resistência de 100% e 47%, respectivamente 10,12 .…”