Antibiotic Use in Children – A Cross-National Analysis of 6 Countries

Published:December 21, 2016DOI:https://doi.org/10.1016/j.jpeds.2016.11.027

      Objectives

      To describe the rates of pediatric antibiotic use across 6 countries on 3 continents.

      Study design

      Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries.

      Results

      A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population.

      Conclusions

      We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.

      Keywords

      Abbreviations**:

      NorPD ( Norwegian Prescription Database)
      To read this article in full you will need to make a payment

      References

        • Holstiege J.
        • Garbe E.
        Systemic antibiotic use among children and adolescents in Germany: a population-based study.
        Eur J Pediatr. 2013; 172: 787-795
        • Stam J.
        • van Stuijvenberg M.
        • Grüber C.
        • Mosca F.
        • Arslanoglu S.
        • Chirico G.
        • et al.
        Antibiotic use in infants in the first year of life in five European countries.
        Acta Paediatr. 2012; 101: 929-934
        • Baquero F.
        • Negri M.C.
        • Morosini M.I.
        • Blázquez J.
        Antibiotic-selective environments.
        Clin Infect Dis. 1998; 27: S5-11
        • Ng S.C.
        • Bernstein C.N.
        • Vatn M.H.
        • Lakatos P.L.
        • Loftus E.V.
        • Tysk C.
        • et al.
        Geographical variability and environmental risk factors in inflammatory bowel disease.
        Gut. 2013; 62: 630-649
        • Risnes K.R.
        • Belanger K.
        • Murk W.
        • Bracken M.B.
        Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children.
        Am J Epidemiol. 2011; 173: 310-318
        • Bailey L.C.
        • Forrest C.B.
        • Zhang P.
        • Richards T.M.
        • Livshits A.
        • DeRusso P.A.
        Association of antibiotics in infancy with early childhood obesity.
        JAMA Pediatr. 2014; 68: 1063-1069
        • Jess T.
        Microbiota, antibiotics, and obesity.
        N Engl J Med. 2014; 371: 2526-2528
        • Greene S.K.
        • Kleinman K.P.
        • Lakoma M.D.
        • Rifas-Shiman S.L.
        • Lee G.M.
        • Huang S.S.
        • et al.
        Trends in antibiotic use in Massachusetts children, 2000-2009.
        Pediatrics. 2012; 130: 15-22
        • Finkelstein J.A.
        • Huang S.S.
        • Kleinman K.
        • Rifas-Shiman S.L.
        • Stille C.J.
        • Daniel J.
        • et al.
        Impact of a 16-community trial to promote judicious antibiotic use in Massachusetts.
        Pediatrics. 2008; 121: e15-23
        • McCaig L.F.
        • Besser R.E.
        • Hughes J.M.
        Trends in antimicrobial prescribing rates for children and adolescents.
        JAMA. 2002; 287: 3096-3102
        • Pichichero M.E.
        Dynamics of antibiotic prescribing for children.
        JAMA. 2002; 287: 3133-3135
        • Vaz L.E.
        • Kleinman K.P.
        • Raebel M.A.
        • Nordin J.D.
        • Lakoma M.D.
        • Dutta-Linn M.M.
        • et al.
        Recent trends in outpatient antibiotic use in children.
        Pediatrics. 2014; 133: 375-385
        • Goossens H.
        • Ferech M.
        • Coenen S.
        • Stephens P.
        Comparison of outpatient systemic antibacterial use in 2004 in the United States and 27 European countries.
        Clin Infect Dis. 2007; 44: 1091-1095
        • Goossens H.
        Antibiotic consumption and link to resistance.
        Clin Microbiol Infect. 2009; 15: 12-15
        • Goossens H.
        • Ferech M.
        • Vander Stichele R.
        • Elseviers M.
        • ESAC Project Group
        Outpatient antibiotic use in Europe and association with resistance: a cross-national database study.
        Lancet. 2005; 365: 579-587
        • Low M.
        • Nitzan O.
        • Bitterman H.
        • Cohen C.
        • Hammerman A.
        • Lieberman N.
        • et al.
        Trends in outpatient antibiotic use in Israel during the years 2000-2010: setting targets for an intervention.
        Infection. 2012; 41: 401-407
        • Lusini G.
        • Lapi F.
        • Sara B.
        • Vannacci A.
        • Mugelli A.
        • Kragstrup J.
        • et al.
        Antibiotic prescribing in paediatric populations: a comparison between Viareggio, Italy and Funen, Denmark.
        Eur J Public Health. 2009; 19: 434-438
        • WHO Collaborating Centre for Drug Statistics Methodology
        ATC index with DDDs 2014.
        (WHO Collaborating Centre, Oslo, Norway) (Accessed December 3, 2015)
        • Lee Y.S.
        • Kwon J.W.
        • Oh O.H.
        • Sohn H.S.
        Temporal decrease in overall antibiotic consumption accompanying antibiotic prescribing rate disclosure policy: evidence from analysis of national health insurance claims data in South Korea.
        Arch Pharm Res. 2014; 37: 1295-1300
        • Lee S.
        • Lee K.
        • Kang Y.
        • Bae S.
        Prevalence of serotype and multidrug-resistance of Streptococcus pneumoniae respiratory tract isolates in 265 adults and 36 children in Korea, 2002-2005.
        Microb Drug Resist. 2010; 16: 135-142
        • Cho S.Y.
        • Baek J.Y.
        • Kang C.-I.
        • Kim S.H.
        • Ha Y.E.
        • Chung D.R.
        • et al.
        Extensively drug-resistant Streptococcus pneumoniae, South Korea, 2011-2012.
        Emerg Infect Dis. 2014; 20: 869-871
        • Iqbal U.
        • Syed-Abdul S.
        • Nguyen P.A.
        • Jian W.S.
        • Li Y.C.
        Physicians antibiotics prescribing behavior in Taiwan.
        Clin Infect Dis. 2015; 60: 1439-1441
        • Wang J.
        • Wang P.
        • Wang X.
        • Zheng Y.
        • Xiao Y.
        Use and prescription of antibiotics in primary health care settings in China.
        JAMA Intern Med. 2014; 174: 1914-1920
        • Versporten A.
        • Bolokhovets G.
        • Ghazaryan L.
        • Abilova V.
        • Pyshnik G.
        • Spasojevic T.
        • et al.
        Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe.
        Lancet Infect Dis. 2014; 3099: 1-7
        • Van Boeckel T.P.
        • Gandra S.
        • Ashok A.
        • Caudron Q.
        • Grenfell B.T.
        • Levin S.A.
        • et al.
        Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.
        Lancet Infect Dis. 2014; 3099: 1-9
        • Kuster S.P.
        • Rudnick W.
        • Shigayeva A.
        • Green K.
        • Baqi M.
        • Gold W.L.
        • et al.
        Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance.
        Clin Infect Dis. 2014; 59: 944-952
        • Fernandes P.
        • Oldach D.
        Antibiotic usage and the development of resistance.
        Clin Infect Dis. 2015; 60: 1139-1140
        • Hicks L.A.
        • Chien Y.-W.
        • Taylor T.H.
        • Haber M.
        • Klugman K.P.
        Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996-2003.
        Clin Infect Dis. 2011; 53: 631-639
        • Bell B.G.
        • Schellevis F.
        • Stobberingh E.
        • Goossens H.
        • Pringle M.
        A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance.
        BMC Infect Dis. 2014; 14: 13
        • Munyaka P.M.
        • Khafipour E.
        • Ghia J.
        External influence of early childhood establishment of gut microbiota and subsequent health implications.
        Front Pediatr. 2014; 2: 109
        • Morgun A.
        • Dzutsev A.
        • Dong X.
        • Greer R.L.
        • Sexton J.
        • Ravel J.
        • et al.
        Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks.
        Gut. 2015; 64: 1732-1743
        • Pottegård A.
        • Broe A.
        • Aabenhus R.
        • Bjerrum L.
        • Hallas J.
        • Damkier P.
        Use of antibiotics in children: a Danish nationwide drug utilization study.
        Pediatr Infect Dis J. 2015; 34: e16-22
        • Gravatt L.A.H.
        • Pakyz A.L.
        Challenges in measuring antibiotic consumption.
        Curr Infect Dis Rep. 2013; 15: 559-563
        • WHO Collaborating Centre for Drug Statistics Methodology
        Guidelines for ATC classification and DDD assignment 2013.
        (Oslo) (Accessed December 5, 2015)
        • Coenen S.
        • Gielen B.
        • Blommaert A.
        • Beutels P.
        • Hens N.
        • Goossens H.
        Appropriate international measures for outpatient antibiotic prescribing and consumption: recommendations from a national data comparison of different measures.
        J Antimicrob Chemother. 2014; 69: 529-534