Antibiotic Resistance of Helicobacter pylori Strains in Japanese Children

Abstract

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 ...

Multicenter Survey of Routine Determinations of Resistance of Helicobacter pylori to Antimicrobials over the Last 20 Years (1990 to 2009) in Belgium

“…Despite the heterogeneity of our population (33), mutations involved in CLR r were comparable to mutations reported previously by other studies in Europe, which were mainly A2142G/43G mutations and various combinations of the wild type as well as point mutations related to the presence of multiple isolates (mixed population) in the same biopsy specimen (1,12,31,37,43,44,49). In contrast with data from many previous studies (1,2,11,24), our study identified the A2142C mutation in some strains from children, probably due to the large number of isolates in our study. The A2142C mutation was associated with a higher level of resistance (CLR MIC of Ͼ256 g/ml), with half of the strains involved being related to patients with at least 2 documented eradication failures.…”

“…Of these strains, 9,430 were isolated from patients who were not previously treated for H. pylori infection (1,527 from children and 7,903 from adults), 1,371 strains were isolated from patients who were previously treated for H. pylori infection (162 from children and 1,209 from adults), and we have no information concerning previous eradication attempts for 24 strains.…”

High Prevalence of Clarithromycin Resistance and cagA , vacA , iceA2 , and babA2 Genotypes of Helicobacter pylori in Brazilian Children

“…Only a few groups have studied mutations involved in clarithromycin resistance in strains obtained from children, and their results are similar to those obtained in our study (5,13,29).…”

Clarithromycin Resistance among Helicobacter pylori Strains Isolated from Children: Prevalence and Study of Mechanism of Resistance by PCR-Restriction Fragment Length Polymorphism Analysis

“…Some papers showed that A2142G was the most frequently detected (48 or 52.5%) (20,23), although some others found that A2143G was more prevalent (55.6 or 56.5%) (5,18). Only a few groups had studied the mutation involved in clarithromycin resistance in strains obtained from children; however, they found results similar to those obtained in our study (8,14,25).…”