Antimicrobial susceptibility of Helicobacter pylori and mechanisms of clarithromycin resistance in strains isolated from patients in Uruguay

Abstract

The prevalence and mechanisms of antibiotic resistance of Helicobacter pylori have not yet been investigated in Uruguay. The objective of this study was to assess the susceptibility of H. pylori to the most frequently used antibiotics and to determine the mechanism of resistance to clarithromycin. Seventy-nine isolates were obtained from gastric biopsies of 50 adult patients during two periods, 2001 and 2006. The former group enrolled the general population (GP), the latter group Afro-descendant (AD) subjects. The minimum inhibitory concentrations of clarithromycin, amoxicillin, tetracycline, metronidazole, and levofloxacin were determined using the E-test technique. Amplification was achieved through PCR and nucleic acid sequencing to detect mutations in the site of action of clarithromycin in the rRNA gene 23S. No amoxicillin or tetracycline-resistant strains were found. Clarithromycin resistance was found in 12% of the patients overall: 19.4% resistance in AD patients and no resistance in the GP group. This difference was statistically significant. The highest resistance was seen with metronidazole (36%), present in similar proportions in the two groups: 36.8% (GP) and 35.5% (AD). One GP patient and one AD patient had levofloxacin-resistant strains. Sequencing analysis of gene 23S rRNA showed that only mutation in position 2143 was presented in all clarithromycin-resistant strains.Key words: H. pylori. Clarithromycin resistance. Uruguay. INTRODUCTIONHelicobacter pylori infection of the gastric mucosa is associated with chronic gastritis, gastro-duodenal ulcer, gastric adenocarcinoma and MALT lymphoma (1-3).Therefore, eradication of the infection is imperative as soon as the presence of the bacteria is confirmed in the setting of one of the above conditions in order to allow ulcers to heal and reduce the risk of developing gastric cancer (4,5).Therapy is based on combinations of antimicrobials and proton pump inhibitors and is usually prescribed empirically, without any susceptibility testing. Although H. pylori may be susceptible to many antibiotics in vitro, in reality, very few agents can be used to treat the infection in vivo. Several therapy schemes have been evaluated for the eradication of H. pylori. Most consensus groups accept that so-called triple therapy (6) is the best choice available. Triple therapy consists of a proton-pump inhibitor combined with two antimicrobials, amoxicillin and clarithromycin as first line agents. However, using this regimen, therapy failures have been reported in up to 15-40% of cases (7-9). Other therapies available for patients with persistent infection include substituting the antimicrobials with metronidazole, tetracycline, or levofloxacin, or adding a bismuth-derived product (10). Tenday sequential therapy: five days of treatment with a proton-pump inhibitor and amoxicillin followed by five days of treatment with the proton-pump inhibitor and two other antibiotics (usually clarithromycin and a 5-nitroimidazole) has also been proposed. A recently published met...

Recent Insights into Antibiotic Resistance inHelicobacter pyloriEradication

“…No AMO-resistant strains were identified in this study, this is most frequently reported with AMO where failure is rarely caused by acquired resistance [49, 50]. Other mutations at position 2142 (A-to-G transition) and position 2182 (C-to-T transition) have been confirmed by analysis of DNA sequencing to be the same as that described at position 2143 and are associated with CLA resistance [51].…”

Prevalence of A2143G and A2144G Point Mutations Responsible for Clarithromycin Resistance among Helicobacter pylori Strains in Bushehr, Iran

“…The global average mutation frequency for the A2143G and A2142G mutations are 69.8% and 11.7%, respectively (23). In many studies, the point mutations A2142G (13,18,23,24) and/or A2142C (4,13,21,24) were not found, and numerous investigations reported that A2143G was the only detected mutation or the most prevalent (4,5,13,17,18,(21)(22)(23)(24)(25). On the other hand, it has been found that the presence of the A2143G point mutation, but not of A2142G or A2142C, significantly lowered the H. pylori eradication rate (26,27).…”

Resistance Rate and Minimum Inhibitory Concentration of Metronidazole Among Helicobacter pylori Strains in Tehran, Iran

“…It appears that the main resistance to metronidazole has been attributed to frequent use of this drug, which is regularly prescribed for other diseases and infections. For this reason, metronidazole has been omitted from first-line experiential therapy strategies in some countries (15). Prolonged amoxicillin-based standard triple therapy was recommended by the European guidelines for countries with > 40% metronidazole resistant H. pylori strains (16).…”