title: The influence of a sustained multifaceted approach to improve antibiotic prescribing in Slovenia during the past decade: findings and implications.
abstract: BACKGROUND
  Rising antibiotic resistance has become an increasing public health problem. There is a well-established correlation between antibiotic consumption and antimicrobial resistance. Consequently, measures to rationalize the prescribing of antibiotics should reduce the resistant strains. Following a 24% increase in antibiotic consumption at the end of the 1990s, multiple activities were designed and introduced by the Health Insurance Institute of Slovenia (ZZZS) and other organizations in Slovenia at the end of 1999. These activities reduced the antibiotic consumption by 18.7% by 2002. These measures have continued.
  
  
  OBJECTIVE
  To study changes in antibiotic utilization from 1995 to 2012 alongside the multiple interventions and their consequences, including changes in resistance patterns.
  
  
  METHODS
  This was a retrospective observational study involving all patients dispensed at least one ZZZS prescription for an antibiotic in Slovenia. Utilization was expressed in defined daily doses per thousand inhabitants per day. Multifaceted interventions were conducted over time involving all key stakeholder groups, that is, the Ministry of Health, ZZZS, physician groups and patients. These included comprehensive communication programs as well as prescribing restrictions for a number of antibiotics and classes.
  
  
  RESULTS
  From 1999 to 2012, antibiotic consumption decreased by 2-9% per year, with an overall decrease of 31%. There were also appreciable structural changes. Overall antibiotic utilization and the utilization of 7 out of 10 antibiotics significantly decreased after multiple interventions. The resistance of Streptococcus pneumoniae to penicillin decreased in line with decreased utilization. However, its resistance to macrolides increased from 5.4 to 21% despite halving of its utilization. The resistance of Escherichia coli to fluoroquinolones doubled from 10 to 21% despite utilization decreasing by a third. Expenditures on antibiotics decreased by 53%.
  
  
  CONCLUSIONS
  Multiple demand-side measures introduced following increased utilization significantly decreased subsequent antibiotic utilization and associated costs. However, there was variable impact on antibiotic resistance. Additional targeted activities are planned to further reduce antibiotic prescribing and resistance.
authors.affiliation: Health Insurance Institute of Slovenia, Miklošičeva 24, SI-1507 Ljubljana, Slovenia.
authors.forename: Jurij
authors.initials: J
authors.lastname: Fürst
authors.forename: Milan
authors.initials: M
authors.lastname: Čižman
authors.forename: Jana
authors.initials: J
authors.lastname: Mrak
authors.forename: Damjan
authors.initials: D
authors.lastname: Kos
authors.forename: Stephen
authors.initials: S
authors.lastname: Campbell
authors.forename: Samuel
authors.initials: S
authors.lastname: Coenen
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.forename: Luka
authors.initials: L
authors.lastname: Fürst
authors.forename: Brian
authors.initials: B
authors.lastname: Godman
mesh_terms: D000900:Anti-Bacterial Agents / Q000191:economics / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D004363:Drug Utilization / Q000639:trends*; D024841:Fluoroquinolones / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D018942:Macrolides / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians'; D012189:Retrospective Studies; D017524:Slovenia; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides
keywords: Slovenia; antibiotic resistance; antibiotic use; drug utilization; multifaceted interventions; policies; rational use of antibiotics