title: The diagnosis and management of antibiotic allergy in children: Systematic review to inform a contemporary approach.
abstract: BACKGROUND
  Adverse drug reactions (ADRs) to antibiotics are commonly reported among children, with some representing genuine drug allergies. Accurate diagnostic tests are required. Drug provocation testing (DPT) is accepted as the gold standard investigation among children with suspected antibiotic allergy. We conducted this review to ascertain the strength of current evidence for using DPT as the first-line investigation for suspected antibiotic allergy among children.
  
  
  METHODS
  Medline was searched in June 2014 for publications investigating antibiotic allergy among children.
  
  
  RESULTS
  865 publications were retrieved and 76 studies selected. ADRs are most common among children of 0-4 years, however only some reveal drug allergies. The best evidence demonstrates that around 0.21% of general paediatric outpatients demonstrate positive antibiotic intradermal (ID) testing or DPTs, while 6.8% of children attending emergency departments for suspected β-lactam allergy may fulfil DPT reactions. Four studies used DPT-based protocols to investigate suspected antibiotic allergy, with two of these conducting ID testing and DPTs across all participants. β-lactam and clarithromycin ID testing had sensitivities of 66.7% and 75%, with positive predictive values of 36% and 33%, respectively, when compared with DPT data.
  
  
  CONCLUSIONS
  Our literature review found four (6%) publications that performed DPTs to subjects' index antibiotic across all participants. No rigorous evidence supports using skin prick, ID or in vitro diagnostic testing; indeed, the testing regimens, extracts and positivity criteria used are inconsistent. We recommend that suspected non-serious antibiotic allergy should be primarily investigated using DPT-based clinical protocols. Data examining their safety, acceptability and diagnostic performance are required.
authors.affiliation: Division of Asthma, Allergy and Lung Biology, Department of Paediatric Allergy, King's College London, London, UK Department of Paediatric Allergy, Guys and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Marrs
authors.affiliation: Division of Asthma, Allergy and Lung Biology, Department of Paediatric Allergy, King's College London, London, UK Department of Paediatric Allergy, Guys and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Fox
authors.affiliation: Division of Asthma, Allergy and Lung Biology, Department of Paediatric Allergy, King's College London, London, UK Department of Paediatric Allergy, Guys and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: Gideon
authors.initials: G
authors.lastname: Lack
authors.affiliation: Division of Asthma, Allergy and Lung Biology, Department of Paediatric Allergy, King's College London, London, UK Department of Paediatric Allergy, Guys and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: George
authors.initials: G
authors.lastname: du Toit
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002648:Child; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D012882:Skin Tests
chemical_list: D000900:Anti-Bacterial Agents
keywords: Adverse Drug Reaction; Allergy; antibiotic; drug hypersensitivity; drug provocation