Antibiotic Stewardship in Hospitals and Primary Care: the Slovenian Experience Prof Bojana Beovic, MD, PhD University Medical Centre Ljubljana Slovenia 1
Déclaration de liens d intérêt avec les industries de santé en rapport avec le thème de la présentation (loi du 04/03/2002) : Intervenant : Bojana Beović Titre : Prof Consultant ou membre d un conseil scientifique L orateur ne souhaite pas répondre OUI NON Conférencier ou auteur/rédacteur rémunéré d articles ou documents: Pfizer, MSD, Alkaloid, Astellas, AstraZeneca, Sandoz OUI NON Prise en charge de frais de voyage, d hébergement ou d inscription à des congrès ou autres manifestations Investigateur principal d une recherche ou d une étude clinique 16es Journées Nationales d Infectiologie, Nancy 16 es JNI, Nancy, du 10 du au 1012 au juin 12 juin 2015 2015 OUI OUI NON NON
A Little Bit of Geography France: 63.5 Mio Inhabitants Slovenia: 2.1 Mio Inhabitants 3
Antibiotic Stewardship is To choose the most effective antibiotic therapy To minimize adverse events To minimize the development of antibiotic resistance At minimal cost McGowan&Gerding, New Horiz 1996; 4: 370-6. ANTIBIOTIC STEWARDSHIP
Aspects of Antibiotic Stewardship OWNERSHIP Non-governemental initiatives: national, international EU state-driven projects/programs National activities University-based initiatives Regional activities Hospital-based activities Industry restriction education structural changes Public TYPE OF ACTIVITY Patients projects programs recommendations legislation structures campaigns research Physician Pharmacists Nurses IT (management) ACTIVITY THE TARGET GROUP
(antimicrobial) AND stewardship in PubMed 1000 800 600 400 200 > 10 years 5 to 10 years last 5 years 0 N of publications
Do the Interventions Work? 7
Do the Interventions Work? Interventions are effective in reducing antimicrobial consumption and / or reducing antimicrobial resistance. 8
Translational Medicine is a discipline that aims to improve the health of individuals and the community by "translating" findings into diagnostic tools, medicines, procedures, policies and education. http://en.wikipedia.or
Determinants of Hospital (Outpatient?) Antibiotic use Sociocultural aspects Socioeconomic aspects Organisational policies Knowledge Attitudes Huscher MEJL, Grol RPTM, van der Meer JW. Lancet ID, 2010; 10: 167-75. 10
Some Facts on Health-care System in France and in Slovenia N of licensed medical doctors per 1000 Inh N of hospital beds per 1000 Inh 4 3 2 1 0 3,3 2,5 France Slovenia 8 6 4 2 0 6,3 4,5 France Slovenia Health-care expenditure in % GDP 20 Hospital discharge rate per 1000 Inh 15 15 10 5 0 11,6 9,4 France Slovenia 10 5 0 16,8 17,1 France Slovenia https://data.oecd.org/health.htm 11
Legislation Infrastructure Local strategy Monitoring of outcomes
Did the Recommendations Have Any Impact? Report on the implementation 2003 (REPORT FROM THE COMMISSION TO THE COUNCIL, 22.12.2005) Almost all countries have national systems for surveillance of antimicrobial use and antibiotic consumption The majority of Member States co-ordinate actions to improve prescribing practices. Sixteen countries have measures in place to enforce regulations for prescription-only use of systemic antimicrobial agents. Most countries have nationally accepted guidelines on appropriate use of antimicrobials for at least some conditions/syndromes Twenty-two countries have a national programme for hospital hygiene and infection control in place, only about half of the countries have legal requirements or recommendations about the number of infection control nurses per hospital bed In all countries education is provided by non-sponsored continuing education, and in almost all of them also through sponsoring by the pharmaceutical industry All but six countries have performed a lay public campaign in some format in the past five years Twenty Member States, two EEA countries, and Bulgaria reported to have an intersectoral mechanism in place and five countries are about to create it. One Member State did not report to create such a mechanism.
Legislation on Antibiotic Stewardship in Slovenia Establishment of the intersectorial mechanisms (National antibiotic committee) 2005: ID physicians, clinical microbiologists, pharmacists, veterinarians, IT, a MoH representative By-laws on antimicrobial consumption surveillance and responsible use of antibiotics 2011: - antimicrobial consumption surveillance is mandatory - antimicrobial stewardship programmes are mandatory in each hospital - audits of antimicrobial stewardship programmes by ICM (since 2013) Official Journal of Slovenia 2011; 21: 1022-5. 14
Infrastructure in Slovenian Hospitals Mandatory AS programme Antimicrobial committee / drug committe or at least one dedicated person with additional training in AS (in small hospitals) 15
Local Strategies in Slovenian Hospitals: Audits in 10 Hospitals, Major Findings (2013-2015) The physicians do not receive information on antimicrobial resistance and consumption in the hospital: 4/10 Poor adherence to guidelines: 7/10 Indication for antibiotics not in the records: 6/10 Poor adherence to antibiotic surgical prophylaxis guidelines: 7/8 No de-escalation: 4/10 Combination of antibiotics in-appropriate: 5/10 Missing antibiotic prescribing improvement plan: 4/10 No guidelines for prescribing CIA antibiotics: 6/10 In-appropriate duration of therapy: 7/10
Recommendations for Antimicrobial Use in Outpatients and Inpatients in Slovenia (1998 2013)
http://ecdc.europa.eu/en/activities/surveillance/esac-net/pages/index.aspx 18
2.17 1.55 http://ecdc.europa.eu/en/activities/surveillance/esac-net/pages/index.aspx 19
In-hospital Antibiotic Consumption: F vs SI The French hospitals (2007): 41.1 DDD/100 patientdays Slovenian hospitals (2007): 50 DDD/100 patient-days Why: Less hospital beds in Slovenia? Amadeo B, et al. J Antimicrob Chemother 2011; 66: 434-42. www.anbico.si 20
Antibiotic Consumption in General and University Hospitals in Slovenia in DDD/100 patient-days 60 50 40 30 Tetraciklini (J01A) Sulfonamidi in trimetoprim (J01E) Makrolidni in piranozidni antibiotiki (linkozamidi) (J01F) Kinolonske protimikrobne učinkovine (J01M) Drugi beta-laktamski antibiotiki (J01D) Druge protimikrobne učinkovine (J01X) Betalaktamski antibiotiki, penicilini (J01C) 20 10 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 All hospitals included from 2003 onwards www.anbico.com 21
Antibiotic Consumption in General and University Hospitals in Slovenia in DDD/1000 admissions 400 350 300 250 Tetraciklini (J01A) Sulfonamidi in trimetoprim (J01E) Makrolidni in piranozidni antibiotiki (linkozamidi) (J01F) Kinolonske protimikrobne učinkovine (J01M) Drugi beta-laktamski antibiotiki (J01D) Druge protimikrobne učinkovine (J01X) Betalaktamski antibiotiki, penicilini (J01C) Aminoglikozidni antibiotiki (J01G) Amfenikoli (J01B) 200 150 100 50 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 All hospitals included from 2003 onwards www.anbico.si 22
Antibiotic Consumption in General and University Hospitals in Slovenia in DDD/1000 admissions 400 350 300 250 Tetraciklini (J01A) Sulfonamidi in trimetoprim (J01E) Makrolidni in piranozidni antibiotiki (linkozamidi) (J01F) Kinolonske protimikrobne učinkovine (J01M) Drugi beta-laktamski antibiotiki (J01D) Druge protimikrobne učinkovine (J01X) Betalaktamski antibiotiki, penicilini (J01C) Aminoglikozidni antibiotiki (J01G) Amfenikoli (J01B) INTENSIFICATION OF TREATMENT 200 150 100 50 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 All hospitals included from 2003 on www.anbico.si 23
Strategies in Ambulatory Antibiotic Use in Slovenia Education of family physicians during the specialisation curriculum Education of family physicians provided by Slovenian Medical Association, ICM at the MoH, Health Insurance Institute) Restricted prescribing of some antibiotics by the Health Insurance Institute (proposed by professionals) Antibiotic pocket-books 24
http://ecdc.europa.eu/en/activities/surveillance/esac-net/pages/index.aspx 25
31.1 14.5 http://ecdc.europa.eu/en/activities/surveillance/esac-net/pages/index.aspx 26
Ambulatory Antibiotic Consumption in Slovenia in DDD/1000 Inh/day (DID) 25 Tetraciklini (J01A) Sulfonamidi in trimetoprim (J01E) Makrolidni in piranozidni antibiotiki (linkozamidi) (J01F) Kinolonske protimikrobne učinkovine (J01M) Drugi beta-laktamski antibiotiki (J01D) Druge protimikrobne učinkovine (J01X) 20 Betalaktamski antibiotiki, penicilini (J01C) Aminoglikozidni antibiotiki (J01G) 15 10 5 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 27
Ambulatory Consumption of Co-amoxiclav in Slovenia in DID 7 6 5 4 3 2 1 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 www.anbico.si 28
Ambulatory Consumption of Co-amoxiclav in Slovenia in DID 7 6 Restriction of co-amoxiclav prescribing, if the indication was not recognized as appropriate, the physician is fined.* 5 4 3 2 1 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 *Level and trend change p< 0.001 www.anbico.si Čižman M, et al. J Glob Antimicrob Resist 2015 29
Ambulatory Consumption of Macrolides in Slovenia in DID 4,50 4,00 3,50 3,00 2,50 Telithromicin (J01FA15) Roksitromicin (J01FA06) Miokamicin (J01FA11) Midekamicin (J01FA03) Klindamicin (J01FF01) Klaritromicin (J01FA09) Eritromicin (J01FA01) Diritromicin (J01FA13) Azitromicin (J01FA10) 2,00 1,50 1,00 0,50 0,00 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 www.anbico.si 30
Ambulatory Consumption of Macrolides in Slovenia in DID 4,50 4,00 3,50 3,00 2,50 2,00 Restriction of macrolides introduced because of high resistance of pneumococci* Telithromicin (J01FA15) Roksitromicin (J01FA06) Miokamicin (J01FA11) Midekamicin (J01FA03) Klindamicin (J01FF01) Klaritromicin (J01FA09) Eritromicin (J01FA01) Diritromicin (J01FA13) Azitromicin (J01FA10) 1,50 1,00 0,50 0,00 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 *decrease after intervention was not significant www.anbico.si Čižman M, et al. J Glob Antimicrob Resist 2015 31
Ambulatory Consumption of Fluoroquinolones in Slovenia in DID 1,80 1,60 1,40 1,20 1,00 Restriction of fluoroquinolones* Pefloksacin (J01MA03) Ofloksacin (J01MA01) Norfloksacin (J01MA06) Moksifloksacin (J01MA14) levofloksacin (J01MA12) Ciprofloksacin (J01MA02) 0,80 0,60 0,40 0,20 0,00 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 *level and trend change <0.001 www.anbico.si Čižman M, et al. J Glob Antimicrob Resist 2015 32
Antibiotic Resistance: France vs Slovenia (2013) 30 25 20 % resistance, sterile samples 15 10 France Slovenia 5 0 E. coli resistant to 3rd gen cephalosporins E. coli resistant to fluoroquinolones K. pneumoniae resistant to 3rd gen cephalosporins K. pneumoniae non-susceptible to carbapenems P. aeruginosa resistant to ceftazidime P. aeruginosa resistant to carbapenems MRSA S. pneumoniae non-susceptible to penicillin S. pneumoniae resistant to macrolides E. faecium resistant to vancomycin EARS-net. http://ecdc.europa.eu/en/healthtopics/antimicrobial_resistance/database/pages/table_reports.aspx 33
Conclusions: Can Slovenia Serve as an Example Good control of antibiotic prescribing in the community, less success in the hospital sector Relatively high resistance rates (poor health-care resources, fewer hospital beds, less effective infection control?) Country-wide antibiotic stewardship activities easier to perform in small countries 34