DARWIN EU® DUS of Antibiotics in the ‘Watch’ category of the WHO AWaRe classification of antibiotics for evaluation and monitoring of use

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective study

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (J01A) TETRACYCLINES

  TETRACYCLINES

  (J01C) BETA-LACTAM ANTIBACTERIALS, PENICILLINS

  BETA-LACTAM ANTIBACTERIALS, PENICILLINS

  (J01DD) Third-generation cephalosporins

  Third-generation cephalosporins

  (J01F) MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS

  MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS

  (J01G) AMINOGLYCOSIDE ANTIBACTERIALS

  AMINOGLYCOSIDE ANTIBACTERIALS

  (J01MB) Other quinolones

  Other quinolones

  (J01XX) Other antibacterials

  Other antibacterials

Population studied

• Short description of the study population:
  The study focused on population-level drug utilisation of antibiotics and patient-level drug utilisation analysis.; The population-level analysis includes individuals with 365 days of database history between 1 January 2012 and 31 December 2021, examining the prevalence and incidence of antibiotic use.; The patient-level analysis includes new users of antibiotics who have not used the antibiotic for 30 days between 1 January 2012 and 31 December 2021, with at least 365 days of visibility prior to their first antibiotic prescription/dispensing.
• Age groups:
  • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  30000000

Study design details

• Study design:
   Population level cohort study (Objective 1, Population-level drug utilisation study on antibiotics) ;  New drug user cohort study (Objective 2, Patient-level drug utilisation analysis with regard to ; duration and indication of antibiotic use)
• Main study objective:
  To investigate the incidence and prevalence of use of antibiotics (from the WHO Watch list) stratified by calendar year, age, sex and country/database during the study period 2012-2021. To explore duration of antibiotic use as well as indication for antibiotic prescribing/dispensing.
• Setting:
  Inpatient and outpatient setting
• Data analysis plan:
  Population-level antibiotic use: Annual period prevalence of antibiotic use and annual incidence rates per 100,000 person years. Patient-level antibiotic use: Large-scale patient-level characterisation will be conducted. Index date will be the date of the first prescription of the specific antibiotic for each person. Frequency of indication at index date will be assessed. Cumulative treatment duration will be estimated and the minimum, p25, median, p75, and maximum will be provided. For all analyses a minimum cell count of 5 will be used when reporting results, with any smaller counts obscured.
• Summary results:
  Of the list of antibiotics from the WHO Watch list (137 individual ingredients), exposure to any of these drugs was reported for 78 antibiotics of this list. Incidence rate were mainly below 100/100.000 PY except for use of ciprofloxacin, clarithromycin, fosfomycin and azithromycin in most of the database. The incidence rate remained stable or decreased over time except for ceftriaxone, cefuroxime, piperacilline-tazobactam and vancomycin that were mainly prescribed in secondary care. For the majority of investigated antibiotics, the incidence increased with age and was comparable by sex. The median duration of use was usually around one week but shorter in secondary care.