Authors Response

Koletzko, Sibylle; Schwarzer, Andrea; Bontem, Patrick; Kalach, Nicolas; on behalf of the co-authors

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e31822b5f23
Letters to the Editor

    To the Editor: We thank Francavilla et al for their interest in our article (1). We agree with their statement that tailored therapy after antibiotic susceptibility testing is successful in children. As previously shown, an eradication rate of 93% was reached in a paediatric cohort with a 1-week tailored triple therapy after excluding patients with a double-resistant strain (2). We also agree that in cases or situations in which susceptibility testing is not feasible or performed, sequential therapy (ST) is superior as a first-line therapy compared with triple therapy as recently confirmed in a study from Poland (3). This is also reflected in the recently published evidence-based guidelines on Helicobacter pylori infection in children (4). Although in randomised controlled trials in adults, ST performs better in the absence of clarithromycin resistance, the success rate still reaches 83.3% in patients infected with clarithromycin-resistant but metronidazole-susceptible strains. The eradication rate drops to 57% with ST in cases harbouring a double-resistant strain, although patient numbers were small even in the combined results from systematic reviews (5). A recent paediatric multicentre study showed a significantly higher eradication rate with tailored triple therapy compared with ST in children infected with a clarithromycin-resistant strain (64% vs 80%, per protocol analysis) (6). The authors concluded that ST should only be proposed in children as a first-line therapy in areas with low clarithromycin resistance rate.

    No results on ST in children infected with double-resistant H pylori strains have been published. Primary double resistance is still rare in children. Only 5.3% were infected with such a strain in a prospective study of 1033 unselected children recruited in 14 European countries before the first treatment (7). After treatment failure, the risk of having a double-resistant strain increased to 15.3% (29/196). The increased risk of double resistance after failed treatment also is reflected in the present study including 64 children with proven double-resistant strains: 46 of them had previously been treated, whereas only 18 were treatment naïve (1). To prove or disprove the performance of ST in paediatric patients, our working group is presently performing an audit on ST as a first-line therapy. An interim analysis of 95 patients in September 2010 showed an overall eradication rate of 84%, with the highest rate in the absence of any antibiotic resistance; however, none of the 4 children infected with a double-resistant strain cleared the infection with ST (unpublished). If these data are confirmed in a larger number of patients, then ST cannot be recommended as a first-line therapy in children in whom susceptibility testing is available and clarithromycin resistance is proven and in children who failed a clarithromycin-based treatment regimen.

    The treatment of patients with multiple resistant H pylori strains will remain a challenge, particularly in children, in whom many of the drugs are not approved. In the light of the poor performance and availabilities of alternative treatment options in children, the eradication rates in our study achieving 66% (95% confidence interval 54–78) in the intention-to-treat analysis, and 73% (95% confidence interval 60–86) per protocol can be considered good. Our concept of a 2-week triple therapy, including esomeprazole, amoxicillin, and metronidazole confirms that in vitro resistance to metronidazole can be overcome, at least in part, in vivo by higher doses and longer treatment duration.

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    1. Schwarzer A, Urruzuno P, Iwanczak B, et al. New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain 1. J Pediatr Gastroenterol Nutr 2011; 52:424–428.
    2. Arenz T, Antos D, Russmann H, et al. Esomeprazole-based 1-week triple therapy directed by susceptibility testing for eradication of Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 2006; 43:180–184.
    3. Albrecht P, Kotowska M, Szajewska H. Sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children: a double-blind, randomized, controlled trial 1. J Pediatr 2011;159:45–9.
    4. Koletzko S, Jones NL, Goodman KJ, et al. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori infection in children 1. J Pediatr Gastroenterol Nutr 2011;53:230–43.
    5. Gatta L, Vakil N, Leandro G, et al. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children 6. Am J Gastroenterol 2009; 104:3069–3079.
    6. Bontems P, Kalach N, Oderda G, et al. Sequential therapy vs tailored triple therapies for Helicobacter pylori infection in children: a prospective, open-label, multicenter study. J Pediatr Gastroenterol Nutr. In press.
    7. Koletzko S, Richy F, Bontems P, et al. Prospective multicenter study on antibiotic resistance of Helicbacter pylori strains obtained from children living in Europe. Gut 2006; 55:1711–1716.
    Copyright 2011 by ESPGHAN and NASPGHAN