The resistance of Helicobacter pylori to the recently available antibiotic treatment regimens has been a growing problem. We investigated the prevalence of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin among 51 H. pylori isolates from Japanese children. In addition, the mutations of the corresponding gene were studied by PCR and restriction fragment length polymorphism analysis. Primary resistance to clarithromycin, metronidazole, and amoxicillin was detected in 29, 24, and 0% of strains, respectively. The eradication rates in clarithromycin-susceptible and -resistant strains were 89 and 56%, respectively (P < 0.05). The prevalence of strains with acquired resistance to clarithromycin (78%) was higher than that of strains with primary resistance (P < 0.01). Among the clarithromycin-resistant strains studied, 92% showed cross-resistance to azithromycin. No acquired resistance to amoxicillin was demonstrated. The A2144G mutation in the 23S rRNA gene was detected in 11 of 12 (92%) clarithromycin-resistant strains tested, whereas the mutation was not detected in any of the 15 susceptible strains. The deletion of the rdxA gene was not demonstrated in any of the strains. The results indicate that a high prevalence of clarithromycin-resistant strains is associated with eradication failure. Testing of susceptibility to clarithromycin is recommended.In adults, Helicobacter pylori plays an important role in the pathogenesis of chronic gastritis, peptic ulcer disease, and possibly, gastric carcinoma. H. pylori infection is also associated with chronic gastritis and duodenal ulcer in children (5, 13). Eradication of the organism not only accelarates ulcer healing (14) but also prevents long-term ulcer relapse (12). Recently, proton pump inhibitor (PPI)-based eradication regimens containing two antibiotics have been demonstrated to have high eradication rates (greater than 90%) (3, 22). Amoxicillin, clarithromycin, and metronidazole are the most frequently used antibiotics for the treatment of H. pylori infection. However, antibiotic resistance frequently causes failure of eradication of H. pylori (1,16,21). The resistance of H. pylori to the recently available antibiotic treatment regimens has been a growing problem. In developed countries, metronidazole resistance is found in 10 to 50% of adult patients infected with H. pylori (1, 10, 11), whereas virtually all strains are resistant to the agent in developing countries (26). On the other hand, although the rates of clarithromycin resistance are relatively low, ranging from 2 to 15% (1, 2, 10, 11, 27), the rate of clarithromycin resistance has been increasing during recent years.With regard to antibiotic resistance, however, there have been few reports of antibiotic resistance in children 2, 17, 23; M. Lopez-Brea, M. Martinez, D. Domingo, and T. Alarcon, abstract from the XIII International Workshop on Gastroduodenal Pathology and Helicobacter pylori, Gut 47(Suppl. 1): A95, 2000], and its clinical significance remains to be established. The purpose ...

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The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first-line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test-and-treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test-and-treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first-line therapy against H. pylori-associated diseases. The guidelines recommend against a "test-and-treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.

Aims: To investigate the existence of Helicobacter pylori in cow's milk as one of the foods which most Japanese children eat. Methods and Results: Detection of H. pylori was demonstrated by the semi‐nested polymerase chain reaction (PCR), a culture method and electron microscopy. Semi‐nested PCR demonstrated the ureA gene of H. pylori in 13 of 18 (72·2%) raw milk samples and in 11 of 20 (55%) commercial pasteurized milk samples. Helicobacter pylori binding immunomagnetic beads with H. pylori‐specific goat anti‐H. pylori antibody was shown by electron microscopy in both raw and pasteurized milk positive for the ureA gene. Helicobacter pylori was cultured in one raw milk sample, whereas it was not cultured in pasteurized milk samples. Conclusions, Significance and Impact of the Study: There is a possibility that cow's milk is a transmission vehicle in childhood H. pylori infection, although we failed to confirm the survival of H. pylori in pasteurized milk.

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Resistance to antibiotics, especially clarithromycin, is the major cause of the failure to eradicate Helicobacter pylori. There are few studies in children concerning fluoroquinolone activity against H. pylori. Primary resistance to antibiotics including fluoroquinolones was studied in 55 H. pylori strains isolated from Japanese children. DNA sequences of the gyrA gene in fluoroquinolone-resistant strains were determined. Twelve strains (21 . 8 %) were resistant to clarithromycin and three (5 . 5 %) were resistant to both levofloxacin and ciprofloxacin. Out of 12 clarithromycin-resistant strains, 11 (91 . 7 %) were susceptible to levofloxacin and ciprofloxacin. Sequence analysis in three fluoroquinolone-resistant strains showed point mutations of the gyrA gene at G271A, G271T and A272G, indicating mutations of the codon Asp91 in the fluoroquinolone-resistance-determining region of the DNA gyrase. The results suggest that fluoroquinolones should be considered as an option for second-or third-line H. pylori eradication therapy in children.