title: Reported rates of diarrhea following oral penicillin therapy in pediatric clinical trials.
abstract: OBJECTIVE
  Antibiotic-associated diarrhea (AAD) is a well-recognized adverse reaction to oral penicillins. This review analyzed the literature to determine the incidence of AAD following amoxicillin, amoxicillin/clavulanate, and penicillin V oral therapy in pediatric clinical trials.
  
  
  METHODS
  An advanced search was conducted in MEDLINE and Embase databases for articles in any language reporting the incidence of AAD following oral penicillin therapy for any indicated infection in children (0-17 years). The search was limited to clinical trials. Articles were excluded if treatment was related to chronic conditions, involved concomitant antimicrobials, or if the dose or number of patients was not specified.
  
  
  RESULTS
  Four hundred thirty-five articles relating to clinical trials were identified (307 from Embase; 128 from MEDLINE). Thirty-five articles reporting on 42 studies were included for analysis. The indications included acute otitis media, sinusitis, pharyngitis, and pneumonia. Thirty-three trials reported on amoxicillin/clavulanate, 6 on amoxicillin, and 3 on penicillin V. In total, the 42 trials included 7729 children who were treated with an oral penicillin. On average, 17.2% had AAD. Data were pooled for each penicillin. The AAD incidence was 19.8% for amoxicillin/clavulanate, 8.1% for amoxicillin, and 1.2% for penicillin V. The amoxicillin/clavulanate data were analyzed according to formulation: pooled-average. The incidence of ADD was 24.6% for the 4:1 formulation, 12.8% for the 7:1 formulation, 19.0% for the 8:1 formulation, and 20.2% for the 14:1 formulation.
  
  
  CONCLUSIONS
  These results demonstrate substantially increased incidence of AAD following use of amoxicillin/clavulanate, compared to use of amoxicillin and penicillin V, as well as varying AAD rates with diffierent amoxicillin/clavulanate formulations. These findings warrant consideration when prescribing. The underlying mechanisms of AAD in children remain unclear.
authors.affiliation: Paediatric Infectious Diseases Unit, St George's Hospital, London, United Kingdom ; Cook County-Loyola-Provident Family Medicine Residency Program, Chicago, Illinois.
authors.forename: Jemima
authors.initials: J
authors.lastname: Kuehn
authors.affiliation: Institute of Pharmaceutical Science & Department of Chemistry, King's College, University of London, London, United Kingdom.
authors.forename: Zareen
authors.initials: Z
authors.lastname: Ismael
authors.affiliation: Institute of Pharmaceutical Science & Department of Chemistry, King's College, University of London, London, United Kingdom.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Long
authors.affiliation: Paediatric Infectious Diseases Research Group, St George's University of London, London, United Kingdom.
authors.forename: Charlotte I S
authors.initials: CI
authors.lastname: Barker
authors.affiliation: Paediatric Infectious Diseases Unit, St George's Hospital, London, United Kingdom ; Paediatric Infectious Diseases Research Group, St George's University of London, London, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
keywords: amoxicillin; amoxicillin/clavulanate; antibiotic; antibiotic-associated diarrhea; oral penicillins; penicillin V