Antibiotic resistance of Helicobacter pylori strains from 106 symptomatic children was evaluated according to EUCAST breakpoints and rate of multidrug resistance (MDR) was analyzed. Overall resistance rates were amoxicillin 7.5%, metronidazole 25.5%, clarithromycin 34.0% and ciprofloxacin 14.1%. There were no significant differences in resistance rates according to patients' age (2–6 and 7–18 years) and sex. Combined resistance rate was 19.8%, including double, triple, and quadruple resistance in 13.2% (14 strains), 5.7% (6) and 0.9% (1) of the strains, respectively. MDR was found in 5.9% (5/84) of the children with gastritis and in two of the four children with celiac disease. The MDR was present in three children aged 4–6 years and in four children aged 10–17 years. The total MDR rate (6.6%) in Bulgarian children in 2012–2021 was higher than those in other studies based on EUCAST breakpoints such as those in pediatric patients in Slovenia in 2011–2014 (3.8%), Lithuania in 2013–2015 (0%) and Spain in 2014–2019 (0%), although being lower than those (20.7% in the untreated and 47.0% in the treated children) in China in 2019. In brief, it is of concern that MDR can strongly limit the choice of H. pylori therapy of one out of fifteen Bulgarian children and that overall resistance to both metronidazole and clarithromycin can hinder the treatment of 15.1% of the pediatric patients. Susceptibility-guided tailored eradication therapy of H. pylori infection should be more frequently implemented in the symptomatic children to avoid risks of both the infection itself and multiple antibiotic treatments.
Hooi JKY , Lai WY , Ng WK , Suen MMY , Underwood FE , Tanyingoh D , et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 2017; 153(2): 420–429.
Kasahun GG , Demoz GT , Desta DM . Primary resistance pattern of Helicobacter pylori to antibiotics in adult population: a systematic review. Infect Drug Resist 2020; 13: 1567–1573.
Tsukamoto T , Nakagawa M , Kiriyama Y , Toyoda T , Cao X . Prevention of gastric cancer: eradication of Helicobacter pylori and beyond. Int J Mol Sci 2017; 18(8): 1699.
Megraud F , Bruyndonckx R , Coenen S , Wittkop L , Huang TD , Hoebeke M , et al. European Helicobacter pylori Antimicrobial Susceptibility Testing Working Group. Helicobacter pylori resistance to antibiotics in Europe in 2018 and its relationship to antibiotic consumption in the community. Gut 2021; 70(10): 1815–1822.
Boyanova L , Hadzhiyski P , Kandilarov N , Markovska R , Mitov I . Multidrug resistance in Helicobacter pylori: current state and future directions. Expert Rev Clin Pharmacol 2019; 12(9): 909–915.
Boyanova L , Hadzhiyski P . Helicobacter pylori infection is associated with anemia, weight loss or both conditions among Bulgarian children. Acta Microbiol Immunol Hung 2020; 67(4): 239–242.
Boyanova L , Gergova G , Nikolov R , Davidkov L , Kamburov V , Jelev C , et al. Prevalence and evolution of Helicobacter pylori resistance to 6 antibacterial agents over 12 years and correlation between susceptibility testing methods. Diagn Microbiol Infect Dis 2008; 60(4): 409–415.
EUCAST-The European Committee on Antimicrobial Susceptibility Testing . Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0. 2021. Available from: http://www.eucast.org.
Adriaenssens N , Bruyndonckx R , Versporten A , Hens N , Monnet DL , Molenberghs G , et al. Quality appraisal of antibiotic consumption in the community, European Union/European Economic Area, 2009 and 2017. J Antimicrob Chemother 2021; 76(12 Suppl 2): ii60–ii67.
Manfredi M , Gismondi P , Maffini V , Bizzarri B , Fornaroli F , Madia C , et al. Primary antimicrobial susceptibility changes in children with Helicobacter pylori infection over 13 years in Northern Italy. Gastroenterol Res Pract 2015; 2015: 717349.
Butenko T , Jeverica S , Orel R , Homan M . Antibacterial resistance and the success of tailored triple therapy in Helicobacter pylori strains isolated from Slovenian children. Helicobacter 2017; 22(5): e12400.
Kori M , Yahav J , Berdinstein R , Shmuely H . Primary and secondary antibiotic resistance of Helicobacter pylori in Israeli children and adolescents. Isr Med Assoc J 2017; 19(12): 747–750.
Mahmoudi S , Mamishi S , Banar M , Keshavarz Valian S , Bahador A , et al. Antibiotic susceptibility of Helicobacter pylori strains isolated from Iranian children: high frequency of A2143G point mutation associated with clarithromycin resistance. J Glob Antimicrob Resist 2017; 10: 131–135.
Dargiene G , Kupcinskas J , Jonaitis L , Vezbavicius M , Kadusevicius E , Kupcinskiene E , et al. Primary antibiotic resistance of Helicobacter pylori strains among adults and children in a tertiary referral centre in Lithuania. APMIS 2018; 126(1): 21–28.
Famouri F , Emadoleslami MS , Riahi R , Saneian H , Nasri P . The sensitivity of H. pylori in gastric tissue samples of children and adolescents to various antibiotics in center of Iran. Int J Pediatr 2018; 6(12): 8685–8696.
Zhang Y , Wen Y , Xiao Q , Zheng W , Long G , Chen B , et al. Mutations in the antibiotic target genes related to clarithromycin, metronidazole and levofloxacin resistance in Helicobacter pylori strains from children in China. Infect Drug Resist 2020; 13: 311–322.
Botija G , García Rodríguez C , Recio Linares A , Campelo Gutiérrez C , Pérez-Fernández E , Barrio Merino A . Antibiotic resistances and eradication rates in Helicobacter pylori infection. An Pediatr (Engl Ed) 2021; S2341-2879(21): 00179–00184.
Li J , Deng J , Wang Z , Li H , Wan C . Antibiotic resistance of Helicobacter pylori strains isolated from pediatric patients in southwest China. Front Microbiol 2021; 11: 621791.
Jiang HY , Zhang X , Zhou YY , Jiang CM , Shi YD . Infection, antibiotic exposure, and risk of celiac disease: a systematic review and meta-analysis. J Gastroenterol Hepatol 2020; 35(4): 557–566.
Mišak Z , Hojsak I , Homan M . Review: Helicobacter pylori in pediatrics. Helicobacter 2019; 24(Suppl 1): e12639.
Shamaly H , Berkowitz D , Rosenthal E , Naveh Y . Efficacy of bismuth-based triple therapy in children with abdominal pain and Helicobacter pylori gastritis. J Pediatr Gastroenterol Nutr 2000; 30(2): 198–200.
Yu L , Luo L , Long X , Liang X , Ji Y , Graham DY , Lu H . High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: a randomized trial. Helicobacter 2019; 24(4): e12596.
Schwarzer A , Urruzuno P , Iwańczak B , Martínez-Gómez MZ , Kalach N , Roma-Giannikou E , et al. ESPGHAN Working Group on Helicobacter pylori infection. New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain. J Pediatr Gastroenterol Nutr 2011; 52(4): 424–428.
Kiyotoki S , Nishikawa J , Sakaida I . Efficacy of vonoprazan for Helicobacter pylori eradication. Intern Med 2020; 59(2): 153–161. https://doi.org/10.2169/internalmedicine.2521-18.
Kusano C , Gotoda T , Suzuki S , Ikehara H , Moriyama M . Safety of first-line triple therapy with a potassium-competitive acid blocker for Helicobacter pylori eradication in children. J Gastroenterol 2018; 53(6): 718–724.
Kakiuchi T , Yamamoto K , Imamura I , Hashiguchi K , Kawakubo H , Yamaguchi D , et al. Gut microbiota changes related to Helicobacter pylori eradication with vonoprazan containing triple therapy among adolescents: a prospective multicenter study. Sci Rep 2021; 11(1): 755.