The A2143G point mutation of Clarithromycin resistance affects H. pylori eradication

The A2143G Point Mutation of Clarithromycin Resistance Affects Helicobacter pylori Eradication To the Editor: Primary clarithromycin resistance is regarded as the main factor reducing the efficacy of Helicobacter pylori eradication therapy. Three point mutations (A2143G, A2142G, and A2142C) are responsible of >90% clarithromycin resistance cases in Western countries1 and some microbiologic observations have found that they are linked with different minimal inhibiting concentration values in vitro. Indeed, high minimal inhibiting concentration values have been associated with either the A2143G or with the A2142G.2,3 However, such a relevant basic issue has been scantly investigated in order that the clinical impact of these studies is largely unknown. On these bases, we performed a retrospective comparison of the prevalence of these point mutations between cured H. pylori and eradication failure patients. Paraffin-embedded antral biopsies of consecutive patients who had received standard triple therapies were retrieved. The A2142C, A2142G, and A2143G point mutations were detected by molecular analysis after DNA extraction by using TaqMan real-time polymerase chain reaction, a method largely described and validated by our group.4 For statistical analysis, the overall rate and the odds ratio (OR) with their 95% confidence intervals were calculated for each observation. Differences between groups were statistically compared by using the Student t test for unpaired data, and the Fisher exact probability test. Differences were considered significant at 5% probability level. The study enrolled 68 consecutive patients, including 46 eradicated and 22 eradication failing patients. The real time-polymerase chain reaction detected a mutate resistant strain in 31 (45.5%) cases. In detail, the A2143G point mutation was present in 22 (70.9%) patients, the A2142G in 6 (19.3%), and the A2142C in 3 (9.8%). According to therapy outcome, a clarithromycin resistant genotype was observed more frequently in eradication failure than cured patients (72.7% vs. 32.6%; P=0.0017; OR= 5.5, 95% CI=1.7-16.9). However, only the prevalence of the A2143G point mutation was significantly higher in those patients who failed eradication as compared with cured patients (54.5% vs. 21.7%; P=0.0066; OR= 4.3, 95% CI=1.412.8), whereas the other 2 point mutations were similarly distributed (A2142G+A2142C: 18.1% vs. 10.8%, respectively; P=0.2; OR= 1.8, 95% CI=0.4-7.5). In conclusion, we found a high prevalence of A2143G point mutation in the patients who failed standard triple therapy, suggesting its potential role in predicting therapy success. Indeed, the prevalence of such a point mutation remained constantly high in the last 15 years in our geographic area.5 Of note, the present study found that A2143G mutate genotype prevalence was significantly higher in those patients who failed therapy as compared with cured patients, being present in 2 each 3 of patients eradication failure patients. On the contrary, the frequency of other point mutations—A2142G and A2142C— was low and a similar prevalence between patients with different therapy outcome was observed; therefore, their presence seems to play a marginal role in the clinical practice.