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Low Antibiotic Resistance of Helicobacter pylori in The Netherlands

To the Editor, Consensus guidelines on treatment of Helicobacter pylori (H. pylori) in adults as well as in children recommend in areas with prevalence of clarithromycin resistance <15–20%, 7–10 days triple therapy with amoxicillin, clarithromycin or metronidazole and a proton-pump inhibitor (PPI), and alternative eradication regimens if the resistance rate is higher [1,2]. With this regimen, eradication rates vary from 60 to 90%. However, the success rate of standard triple therapy for H. pylori eradication is decreasing worldwide due to increasing antimicrobial resistance of H. pylori to clarithromycin and/or metronidazole, probably because of the increasing use of clarithromycin for respiratory infections (especially in children) and the use of metronidazole for parasitic infections. Alternative regimens containing tetracyclines or bismuth are not allowed in children in many countries. Currently, sequential therapy is a topic of research in adults as well as in children to improve the eradication rate. Dutch guidelines recommend test-and-treat, which is safe and as effective as direct endoscopy, in the absence of alarm symptoms in persons <45 years of age [3]. However, data on resistance of H. pylori isolated from adults are only available until 2003, [4] and resistance in children has never been investigated. In order to estimate whether the test-and-treat approach is justified in the Netherlands, we analyzed the prevalence of resistance to clarithromycin and metronidazole in H. pylori -positive cultures from biopsies from the gastric antrum and/or corpus of adults and children (<18 years of age) from January 2000 to December 2009. For most adult patients, it was unknown whether or not they had undergone noninvasive testing before and whether or not they had been treated before. None of the children had been treated for H. pylori before the first endoscopy. Cultures of biopsies for H. pylori were carried out, and H. pylori positivity was determined with a Gram stain and a positive oxidase, catalase, and urease test. Strains were considered clarithromycin sensitive if MIC ≤ 0.25, metronidazole sensitive if MIC ≤ 8 mg/L, intermediate if MIC > 8 and MIC ≤ 16 mg/L, and resistant if MIC > 16 mg/L, according to the Eucast-criteria (www.eucast.org). Demographic data and results of resistance to antibiotics are summarized in Table 1. From 1152 patients, 1214 cultures were positive for H. pylori. Susceptibility of clarithromycin and metronidazole could be determined in 1088 (90%) and 1095 (90%) cultures, respectively. All clarithromycin-resistant strains in children were detected in the period after 2004, while metronidazole-resistant strains were divided equally over the whole period. During the study period, the resistance to clarithromycin increased from <5 to 8.5–9.4% in adults and resistance to metronidazole increased from 7–33 to 20.7–22.9%. In second occasion biopsies, H. pylori from 4 of 41 cultures from adults became resistant to clarithromycin and 4 to metronidazole. In third occasion biopsies, 1 and 2 strains from adults became resistant to clarithromycin and metronidazole, respectively.