High prevalence of clarithromycin resistance and effect on Helicobacter pylori eradication in a population from Santiago, Chile: cohort study and meta-analysis

A Arenas, C Serrano, L Quiñones, P Harris, M Sandoval, M Lavanderos, R Sepúlveda, S Maquilón, A Echeverría, C Ríos, E Fuentes-López, L Rojas, A Jorquera, M Pizarro, M C Camargo, A Riquelme, A Arenas, C Serrano, L Quiñones, P Harris, M Sandoval, M Lavanderos, R Sepúlveda, S Maquilón, A Echeverría, C Ríos, E Fuentes-López, L Rojas, A Jorquera, M Pizarro, M C Camargo, A Riquelme

Abstract

Helicobacter pylori (H. pylori) eradication using standard triple therapy (STT) with proton pump inhibitors (PPI), amoxicillin and clarithromycin (CLA) has been the standard in Latin America. However, CLA resistance is a rising problem affecting eradication rates. Genetic polymorphisms of CYP2C19, a PPI metabolizer may also affect eradication. The primary aims of this study were to evaluate the effect of clarithromycin resistance on H. pylori eradication in a population from Santiago, and to establish the pooled clarithromycin resistance in Santiago, Chile. Symptomatic adult patients attending a tertiary hospital in Santiago were recruited for this study. CLA resistance and the polymorphisms of CYP2C19 were determined on DNA extracted from gastric biopsies, using PCR. The STT was indicated for 14 days and eradication was determined by a urea breath test 4-6 weeks after therapy. A meta-analysis of CLA resistance studies among adult residents in Santiago was performed. Seventy-three out of 121 consecutive patients had positive rapid urease test (RUT) and received STT. Sixty-nine patients (95%) completed the study. The H. pylori eradication rate was 63% and the prevalence of CLA resistance was 26%. According to the CYP2C19 polymorphisms, 79.5% of the RUT-positive patients were extensive metabolizers. Multivariable analyses showed that only CLA resistance was significantly and inversely associated with failure of eradication (OR: 0.13; 95% confidence interval [95% CI], 0.04-0.49). A meta-analysis of two previous studies and our sample set (combined n = 194) yielded to a pooled prevalence of CLA resistance of 31.3% (95% CI 23.9-38.7). Our study shows that CLA resistance is associated with failure of H. pylori eradication. Given the high pooled prevalence of CLA resistance, consideration of CLA free therapies in Santiago is warranted. We could recommend bismuth quadruple therapy or high-dose dual therapy, according to bismuth availability. Further studies need to evaluate the best therapy.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Forest plot of the proportion of CLA resistance from studies conducted in adult populations, Santiago, Chile. Symbols: ■ single studies included in the meta – analysis; − confidence interval (CI); ◇  overall pool estimated; and a reference dashed vertical line was added at 0.15 (15%) to represent the value recommended by the consensus of Maastricht V/Florence on the management of H. pylori.

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