Mutations in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pyloriisolates in Brazil

Ribeiro, Vitiello Lea, Miranda, Benvengo, Godoy, Mendonca Sergio, Pedrazzoli, Pedrazzoli José

Description

Resistance of Helicobacter pylori to clarithromycin has been associated with A2142G and A2143G point mutations in the 23S rRNA gene. Thus, the purpose of the present study was to determine the prevalence of each mutation in 52 clarithromycin-resistant H. pylori strains and to characterize the influence each type of mutation on the MIC. Methods The MIC for clarithromycin was determined by the agar dilution method, and the point mutations of H. pylori were detected by PCR followed by restriction fragment length polymorphism. Results Clarithromycin MICs ranged from 2 to >256 microgram ml -1 among the 52 strains included in this study. Both the A2142G and the A2143G mutations were present in 94.2% of clarithromycin-resistant H. pylori strains examined. A relationship was observed between the presence of the A2142G mutation and the highest MIC values (p = 0.01). Conclusion In an H. pylori- infected population, the A2142G mutation may incur to a greater probability of treatment failure if clarithromycin is used.

Informations

• Publié par: biomed
• Publié le: 01 janvier 2003
• Nombre de lectures: 17
• Langue: English

Extrait

Annals of Clinical Microbiology and Antimicrobials

BioMedCentral

Open Access Research Mutations in the 23S rRNA gene are associated with clarithromycin resistance inHelicobacter pyloriisolates in Brazil Marcelo L Ribeiro, Lea Vitiello, Maira CB Miranda, Yune HB Benvengo, Anita PO Godoy, Sergio Mendonca and José Pedrazzoli Jr*

Address: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil Email: Marcelo L Ribeiro  [e-mail]; Lea Vitiello  [e-mail]; Maira CB Miranda  [e-mail]; Yune HB Benvengo  [e-mail]; Anita PO Godoy  [e-mail]; Sergio Mendonca  [e-mail]; José Pedrazzoli*  [e-mail] * Corresponding author

Published: 21 November 2003 Received: 06 October 2003 Accepted: 21 November 2003 Annals of Clinical Microbiology and Antimicrobials2003,2:11 This article is available from: http://www.annclinmicrob.com/content/2/1/11 © 2003 Ribeiro et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Abstract Background:Resistance ofHelicobacter pylorito clarithromycin has been associated with A2142G and A2143G point mutations in the 23S rRNA gene. Thus, the purpose of the present study was to determine the prevalence of each mutation in 52 clarithromycinresistantH. pyloristrains and to characterize the influence each type of mutation on the MIC.

Methods:The MIC for clarithromycin was determined by the agar dilution method, and the point mutations ofH. pyloriwere detected by PCR followed by restriction fragment length polymorphism. 1 Results:among the 52 strainsClarithromycin MICs ranged from 2 to >256 microgram ml included in this study. Both the A2142G and the A2143G mutations were present in 94.2% of clarithromycinresistantH. pyloristrains examined. A relationship was observed between the presence of the A2142G mutation and the highest MIC values (p = 0.01). Conclusion:In anH. pyloriinfected population, the A2142G mutation may incur to a greater probability of treatment failure if clarithromycin is used.

Background Helicobacter pyloriis a gramnegative bacterium that colo nizes the human stomach and is associated with a variety of digestive diseases, such as chronic gastritis and peptic ulcer disease [1,2]. Infection withH. pylorican be effec tively treated by the combination of a proton pump inhib itor with multiple antibiotics. The firstline regimen consists mainly of a triple therapy, and clarithromycin is one of the most widely used components. Although the bacteria can be eradicated in up to 90% of patients, side effects, poor compliance and resistance to the antibiotics used are common causes of treatment failure [3,4].

The increasing use of clarithromycin has resulted in the development of resistance. The prevalence of resistant strains varies among countries and ranges from 1% in Norway [5] to 29% in Japan [6]. The mechanism of resist ance to clarithromycin inH. pyloriseems to be due to a decrease in binding of macrolides to the ribosome, associ ated with point mutations within the peptidyltransferase encoding region of 23S rRNA gene [7,8]. Three major point mutations in two positions have been described in which an adenine residue is replaced by a guanine or a cytosine residue at adjacent positions: A2142C, A2142G, and A2143G [710]. Thus, the purpose of the present

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