title: Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis.
abstract: OBJECTIVE
  To systematically review studies investigating the prevalence of antibiotic resistance in urinary tract infections caused by Escherichia coli in children and, when appropriate, to meta-analyse the relation between previous antibiotics prescribed in primary care and resistance.
  Systematic review and meta-analysis. Pooled percentage prevalence of resistance to the most commonly used antibiotics in children in primary care, stratified by the OECD (Organisation for Economic Co-operation and Development) status of the study country. Random effects meta-analysis was used to quantify the association between previous exposure to antibiotics in primary care and resistance.
  
  
  METHODS
  Observational and experimental studies identified through Medline, Embase, Cochrane, and ISI Web of Knowledge databases, searched for articles published up to October 2015.
  
  
  METHODS
  Studies were eligible if they investigated and reported resistance in community acquired urinary tract infection in children and young people aged 0-17. Electronic searches with MeSH terms and text words identified 3115 papers. Two independent reviewers assessed study quality and performed data extraction.
  
  
  RESULTS
  58 observational studies investigated 77,783 E coli isolates in urine. In studies from OECD countries, the pooled prevalence of resistance was 53.4% (95% confidence interval 46.0% to 60.8%) for ampicillin, 23.6% (13.9% to 32.3%) for trimethoprim, 8.2% (7.9% to 9.6%) for co-amoxiclav, and 2.1% (0.8 to 4.4%) for ciprofloxacin; nitrofurantoin was the lowest at 1.3% (0.8% to 1.7%). Resistance in studies in countries outside the OECD was significantly higher: 79.8% (73.0% to 87.7%) for ampicillin, 60.3% (40.9% to 79.0%) for co-amoxiclav, 26.8% (11.1% to 43.0%) for ciprofloxacin, and 17.0% (9.8% to 24.2%) for nitrofurantoin. There was evidence that bacterial isolates from the urinary tract from individual children who had received previous prescriptions for antibiotics in primary care were more likely to be resistant to antibiotics, and this increased risk could persist for up to six months (odds ratio 13.23, 95% confidence interval 7.84 to 22.31).
  
  
  CONCLUSIONS
  Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E coli is high, particularly in countries outside the OECD, where one possible explanation is the availability of antibiotics over the counter. This could render some antibiotics ineffective as first line treatments for urinary tract infection. Routine use of antibiotics in primary care contributes to antimicrobial resistance in children, which can persist for up to six months after treatment.
authors.affiliation: Centre for Academic Primary Care, NIHR School for Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK ashley.bryce@bristol.ac.uk.
authors.forename: Ashley
authors.initials: A
authors.lastname: Bryce
authors.affiliation: Centre for Academic Primary Care, NIHR School for Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Hay
authors.affiliation: Centre for Academic Primary Care, NIHR School for Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
authors.forename: Isabel F
authors.initials: IF
authors.lastname: Lane
authors.affiliation: Centre for Academic Primary Care, NIHR School for Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
authors.forename: Hannah V
authors.initials: HV
authors.lastname: Thornton
authors.affiliation: Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital of Wales, Cardiff CF14 4XW, UK.
authors.forename: Mandy
authors.initials: M
authors.lastname: Wootton
authors.affiliation: NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London W12 0NN, UK.
authors.forename: Céire
authors.initials: C
authors.lastname: Costelloe
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D064887:Observational Studies as Topic; D015995:Prevalence; D011320:Primary Health Care; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D019980:Amoxicillin-Potassium Clavulanate Combination