JOURNAL TRANSCRIPT
y r a Measuring antimicrobial consumption: r b i why, what and how? L e r u t c e r L o e h t n i u l a n O by D © I M C S E ESCMID Postgraduate Education Course Antimicrobial Stewardship Developing, Implementing & Measuring
Seva (Barcelona), Spain, 8 – 10 May 2014
Håkan Hanberger, MD, Professor Infectious Diseases, Linköping University Swedish Reference Group of Antibiotics - EUCAST, Strama - the Swedish strategic programme against antibiotic resistance Swedish Medical Agency Scientific Committe,
Bojana Beović, MD, Professor Infectious Diseases Ljubljana University, Slovenia
Measuring antimicrobial consumption: y r why, what and how? ra
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r u t c e r L o e h t n i u l a n O by D © I M
•Identify areas for improvement •Compare antimicrobial use across wards and hospitals to motivate change (benchmarking wards, hospitals, regions, countries…) •Capture attention of prescribers/politicians/public on rational use of antibiotics •To measure the effect of interventions (follow trends) •To study the relatonship between consumption and resistance
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Measuring antimicrobial consumption: y r why, what and how? ra
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r u t Antibiotic consumption inchumans* e r L - Primary care (90% of human ABC) o e h t n - Longterm carelifacilitiesu(HUB for ABR a n transmission) O by D general - Hospitals: wards I © M - Hospitals: specialized wards, e.g. ICUs C S E Note: Consumption in animals not included in this presentation
Measuring antimicrobial consumption: y r why, what and how? ra
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• Numerator: – Weight (g or kg or units of treatment) – Vials – Agent days – Courses/Recipe – Treatment periods – Percentage of patients exposed to antimicrobials – Antibiotic days or Days of Treatment (DOT) – DDD (Defined Daily Dose) – PDD (Prescribed Daily Dose) • Denominator: – Per month or year – Per 1000 inhabitants-days – Per 100 or 1,000 patient-days – Per 100 or 1,000 administrative bed-days – Per 100 or 1,000 occupied bed-days – Per 100 or 1,000 admissions – Per 100 or 1,000 discharges – Per month/occupied bed – Per Thousand Finished Consultant Episodes
r u t c e r L o e h t n i u l a n O by D © I M
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Courtesy: Herman Goossens
Measuring antimicrobial consumption: y r why, what and how? ra National level Outpatients (all) Hospitals (all)
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r u t c e r L o Local level e Outpatient: Primaryn care centre th i au Hospital: wardsnl O by D I © Patient level M Outpatients per indication: UTI, pneumonia etc C S Hospital patients per indication: Ventilator associated pneumonia E (VAP), Catheter Related Blood stream Infection (CRBI) etc
y Definition of r a r b i Defined Daily Dose (DDD L WHO):
e r u t c e r DDD is the assumedLaverage o e h maintenance dose per day for a drug t n i u l a used for its main indication in adults. n O by D © I M C S E
DDD per 1000 inhabitants per day
y r a r b i L *DDD Defined Daily Doses e r per 1000 inhabitants u per day t c e r L o e h t n i u l a n O by D © I M
Antibiotic Consumption in EU - Outpatients
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H. Goossens Lancet 2005; 365: 579–87
DDD per 1000 inhabitants per day Outpatients – National Level
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Antibiotics consumption in Sweden, 2006-2011 Source Apotekens Service AB, Concise
DDD per 1000 inhabitants per day
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r u t c e r L o e h t n i u l a n O by D © I M
16 14 12 10
J01 exkl metenamin
8 6 4 2 0
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glidande medelvärde 12 månader bakåt
DDD per 1000 inhabitants per day Outpatients – National Level
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Antibiotics consumption in Sweden, 2006-2011 Source Apotekens Service AB, Concise
DDD per 1000 inhabitants per day
18
r u t c e r L o e h t n i u l a n y O bAdvantage of measuring the DDDs access D © •• Easy I Low cost M
16 14 12 10
J01 exkl metenamin
8 6 4 2 0
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glidande medelvärde 12 månader bakåt
• Not time consuming • Sustainable • Useful for bench marking • May be used for measuring effect of interventions = Time series analysis
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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r u t c Guided Tour e r L o e h t n i u l DDD a n O byon D © I http://www.whocc.no/atc_ddd_index M
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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The basic definition of the defined daily dose (DDD) is: The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults.
r u t c e r L o e h t n i u l a n O by D © I M
•A DDD will only be assigned for drugs that already have an ATC code.
•It should be emphasised that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Doses for individual patients and patient groups will often differ from the DDD and will necessarily have to be based on individual characteristics (e.g. age and weight) and pharmacokinetic considerations. •For the optimal use of drugs, it is important to recognise that genetic polymorphism due to ethnic differences can result in variations in pharmacokinetics of drugs. The DDD should reflect the global dosage irrespective of genetic variations of drug metabolism.
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•Drug consumption data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. The DDD provide a fixed unit of measurement independent of price and dosage form (e.g. tablet strength) enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups. http://www.whocc.no/atc_ddd_index/
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
y r a r b i L e
The basic definition of the defined daily dose (DDD) is: The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults.
r u t c e Therapeutic r Anatomical Chemical L o e h (ATC) classification for medicines t n i u l a n O by D © I M
•A DDD will only be assigned for drugs that already have an ATC code.
•It should be emphasised that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Doses for individual patients and patient groups will often differ from the DDD and will necessarily have to be based on individual characteristics (e.g. age and weight) and pharmacokinetic considerations.
•For the optimal use of drugs, it is important to recognise that genetic polymorphism due to ethnic differences can result in variations in pharmacokinetics of drugs. The DDD should reflect the global dosage irrespective of genetic variations of drug metabolism.
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•Drug consumption data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. The DDD provide a fixed unit of measurement independent of price and dosage form (e.g. tablet strength) enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups. http://www.whocc.no/atc_ddd_index/
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
y r a r b i L e
The basic definition of the defined daily dose (DDD) is: The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults.
r u t c e r L o e h t n i u l a n O by D © I M
•A DDD will only be assigned for drugs that already have an ATC code.
•It should be emphasised that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Doses for individual patients and patient groups will often differ from the DDD and will necessarily have to be based on individual characteristics (e.g. age and weight) and pharmacokinetic considerations. •For the optimal use of drugs, it is important to recognise that genetic polymorphism due to ethnic differences can result in variations in pharmacokinetics of drugs. The DDD should reflect the global dosage irrespective of genetic variations of drug metabolism.
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•Drug consumption data presented in DDDs only give a rough estimate of consumption and not an exact picture of actual use. The DDD provide a fixed unit of measurement independent of price and dosage form (e.g. tablet strength) enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups. http://www.whocc.no/atc_ddd_index/
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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r u t c e r L o defined daily dose is a unit of measurement e h t n and does not necessarily reflect the i u l a n recommended or Prescribed Daily Dose. O by D © I M
Last updated: 2013-12-19
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http://www.whocc.no/atc_ddd_index/
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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DDDWHO
r u t c e r L o defined daily dose is a unit of measurement e h t n and does not necessarily reflect the i u l a n recommended or Prescribed Daily Dose. O by D © I M
ORAL DDDWHO (1g ciprofloxacin) PARENTERAL DDDWHO (0.5g ciprofloxacin)
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DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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DDDWHO
r u t c e r L o defined daily dose is a unit of measurement e h t n and does not necessarily reflect the i u l a n recommended or Prescribed Daily Dose. O by D © I M
ORAL DDDWHO (1g ciprofloxacin) PARENTERAL DDDWHO (0.5g ciprofloxacin)
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Most common precribed daily dose ORAL Tabl. Ciprofloxacin 0.5g x 2 (1g/24h) BUT PARENTERAL Inf Ciprofloxacin 0.4g x 2, i.v.(0.8g/24h)
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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DDDWHO
r u t c e r L o defined daily dose is a unit of measurement e h t n and does not necessarily reflect the i u l a n recommended or Prescribed Daily Dose. O by Parenteral ciproflox. D © I PDD 0.8g M
ORAL DDDWHO (1g ciprofloxacin) PARENTERAL DDDWHO (0.5g ciprofloxacin)
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DDDWHO 0.5g
Most common precribed daily dose ORAL Tabl. Ciprofloxacin 0.5g x 2 (1g/24h) BUT PARENTERAL Inf Ciprofloxacin 0.4g x 2, i.v.(0.8g/24h)
DDD Defined Daily Dose Guided Tour on http://www.whocc.no/atc_ddd_index
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DDDWHO
r u t c e r L o defined daily dose is a unit of measurement e h t n and does not necessarily reflect the i u l a n recommended or Prescribed Daily Dose. O by Parenteral ciproflox. D © I PDD 0.8g M
ORAL DDDWHO (1g ciprofloxacin) PARENTERAL DDDWHO (0.5g ciprofloxacin)
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Most common precribed daily dose ORAL Tabl. Ciprofloxacin 0.5g x 2 (1g/24h) BUT PARENTERAL Inf Ciprofloxacin 0.4g x 2, i.v.
DDDWHO 0.5g = 1.6 (correction factor) to convert. DDDWHO to PDD
• • •
y r DDD and Denominators a r b i L e r u t c e r L o e h t n i u l a n O by D © I M C S
Drug consumption figures should preferably be presented as numbers of DDDs/1000 inhabitants/day or when in-hospital drug use is considered, as DDDs per 100 bed days or admissions. Sales or prescription data presented in DDD/1000 inhabitants/day may provide a rough estimate of the proportion of the population within a defined area treated daily with certain drugs. – – –
E
For example, the figure 10 DDDs/1000 inhabitants/day indicates that 1% of the population on average gets a certain treatment daily. For example, 5 DDDs/inhabitant/year indicates that the consumption is equivalent to the treatment of every inhabitant with a 5 days course during a certain year. Alternatively, if the standard treatment period is known, the total number of DDDs can be calculated as the number of treatment courses, and the number of treatment courses can then be related to the total population.
http://www.whocc.no/atc_ddd_index/
DDD per 1000 inhabitants per day
Outpatients – National Level Antibiotics consumption in Sweden , DDD per 1000 inhabitants per day, 1974-2001 Source : Apoteket AB
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r u t c e r L o e h t n i u l a n O by D © I M
Strama campaign rational use
DDD per 1000 inhabitants per day
Outpatients – National Level Antibiotics consumption in Sweden , DDD per 1000 inhabitants per day, 1974-2001 Source : Apoteket AB
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r u t c e r L o Strama campaign e h t n u i l rational use a n y used for Oinh./daybwere DDD/1000 D effect measuring of the interventions (time I © series analysis) M
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r u t c e r HOSPITAL L o e h t n i u l a n O by D © I M
DDD per 1000 inhabitants per day
y r a Antibiotic consumption in Swedish Hospitals r b Trends 2000-2011 i L e r u t c e r L o e h t n i u l a n O by D © I M C S E 1.8
Source Apotekens Service AB, Concise
DDD per 1000 inhabitants per day
1.6
1.4
1.2
1
J01 exkl metenamin
0.8
0.6
0.4
0.2
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
DDD per 1000 inhabitants per day
y r a r Strama campaign, rational useb i L e r u t c e r L o e h t n i u l a n O by D © I M Antibiotics consumption in Swedish Hospitals Trends 2000-2011 Source Apotekens Service AB, Concise
1.8
DDD per 1000 inhabitants per day
1.6
1.4
1.2
1
J01 exkl metenamin
0.8
0.6
C S E 0.4
0.2
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
DDD per 1000 inhabitants per day
y r a r Strama campaign, rational useb i L e r u t c e r L o e h t n i u l a Our analysis basedn on point prevalence studies showed an yconsumption Oincreased overestimation of b D © I Explanations/Errors M 1.New mix of drugs with lower DDDs than prescribed daily doses C S (PDDs) E2.Increased prescribed daily doses (PDDs) to save lifes in severe 1.8
Antibiotics consumption in Swedish Hospitals Trends 2000-2011 Source Apotekens Service AB, Concise
DDD per 1000 inhabitants per day
1.6
1.4
1.2
1
J01 exkl metenamin
0.8
0.6
0.4
0.2
sepsis/septic shock 3.Increased prescribed daily doses (PDDs) to reduce emergence 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 of resistance
DDD per 1000 inhabitants per day
y r a r Strama campaign, rational useb i L e r u t c e r L o e h t n i u l a n Advantage of measuring the DDDs in hospitals •Useful for benchO markingby Dfor measuring •May be used effect of antibiotic I © = Time series analysis – but be aware of stewardship M errors C S E Antibiotics consumption in Swedish Hospitals Trends 2000-2011 Source Apotekens Service AB, Concise
1.8
DDD per 1000 inhabitants per day
1.6
1.4
1.2
1
J01 exkl metenamin
0.8
0.6
0.4
0.2
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
Strengths and weakness measuring DDDs • Strengths DDD
-
Aggregates all doses, packages Good to follow volume changes with same mix Easy access Low cost Not time consuming Sustainable Useful for bench marking Allow fair comparisons among countries, hospitals and wards Strict definition of oral and i.v. products May be used for measuring effect of interventions = Time series analysis
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• Weaknesses DDD -
Influenced by denominator (adm-days vs admissions) Does not always correspond to the dose used in routine practice (septic shock, intensive care, renal failure etc.) Corrections are made by WHO (DDD will change over time) Reported volume distributed not equal to given In hospitals, it does not allow extrapolation to the number of patient exposed (combinations of antimicrobials are common) Cannot be used in pediatric and neonatal hospitals/wards
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r u t c e r L o e h t n i u l a n O by D © I M -
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-
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Inpatient use: per patient-days or per admission? The Dutch University Hospitals
r u t c e r L o e h t n i u l a n O by D © I M
Length of stay decreased from 6.27 to 4.5 days: intensification of treatment, the patients received antibiotics all the time in hospital, and they are discharged afterwards
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Intensification of treatment is necessary to accomodate more patients, which leads to the increase in admissions (+25.9%): DDD/100 admissions decreased Kwint HM, et al. J Antimicrob Chemother 2012; 67: 22283-8.
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Inpatient use: per patient-days or per admission? The Dutch University Hospitals
r u t c e r What does the L intensification o e h of antibiotic treatment in t n i u l a hospitals mean for the n y O b antimicrobial resistance?! D I © M C S E
Length of stay decreased from 6.27 to 4.5 days: intensification of treatment, the patients received antibiotics all the time in hospital, and they are discharged afterwards Intensification of treatment is necessary to accomodate more patients, which leads to the increase in admissions (+25.9%): DDD/100 admissions decreased Kwint HM, et al. J Antimicrob Chemother 2012; 67: 22283-8.
y r a r b i L • The Dutch hospitals (2009): 69.8 DDD/100 patient-days e r • The French hospitals (2007): 41.1 DDD/100 patient-days u t c e r 0.97 DDD/TID L • The Dutch inpatient antibiotic consumptiono(2011): e h t • The French inpatient consumption (2011 ): 2.02 DDD/TID (+208%) n i u l a n O by ? D I © Hospital beds per 100,000 Inh (2009): M C France: 637.2 (+ 43%) S The Netherlands: 465.7 E Benchmarking inpatient antibiotic use: does the number of hospital beds matter?
http://epp.eurostat.ec.europa.eu http://www.ecdc.europa.eu/en/activities/surveillance/esac-net/pages/index.aspx Amadeo B, et al. J Antimicrob Chemother 2011; 66: 434-42. Kwint HM, et al. J Antimicrob Chemother 2012; 67: 2283-8.
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r u t c e r L Number of antibiotic o e h t n i prescriptions or recipe/1000 inh./year u l a n O by D © I M C S E
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Number of antibiotic prescriptions (or recipe) /1000 inhabitants/year
Antibiotic consumption (J01 exkl methenamine) in different age groups Community care in Sweden 1987 - 2009, prescriptions per 1000 inhabitants and year Data source: The National Board of Heatlh and Welfare and The National Corp. of Swedish Pharacies
r u t c e r L o e h t n i u l a n O by D © I M
1400
Prescriptions/1000 inhabitants/year
1200 1000 800 600 400
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200 0
Strama strated with Intervention - Rational use no AB for viral inf.
0 - 4 years 5 - 14 years 15 - 64 years 65 - 99 years
Change in antibiotic prescriptions (or recipe)/1000 inhabitants/year Ages 0-4, 5-14, 15-64, 65- (all Swedish recipe)
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r u t c -70 % e r L o e h t n i u l a n O by D © I M
-58 %
Source: Mats Erntell
Change (1987 – 2013) in antibiotic prescriptions (or recipe)/1000 inhabitants/year Ages 0-4, 5-14, 15-64, 65- (all Swedish recipe)
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Reimbursement to counties decreasing prescriptions (approx 500.000 EUR/year)
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r u t c -70 % e r L o e h t n i u l a n O by D © I M
-58 %
Source: Mats Erntell
y r Prescribed daily dose (PDD) a r b i L e r Data source u t c •Electronic system Le r o e h t •Point Prevalence studies (PPS) n i u l a n •Charts – retrospectively O by D © I M C S E
Prescribed Daily Doses (PDDs)
• • • •
y r a r b i Defined locally (hospital, ward) or within aL group of hospitals e r u t PDD = average prescribed dosec on the main indication r (in a hospital, ward or groupLofehospitals) o e h t n i u l Grams (or I.U.) active substance a n O by Do NOT allow comparisons! Dinter-hospital I © M C S E
No. PDDs =
No. packages x No. tablets per package x No. g per tablet PDD of antimicrobial in grams
The European Surveillance of Antimicrobial Consumption (ESAC) point prevalence survey of antibacterial use in 20 European hospitals in 2006.
y r a r Fig 2. Ratio of prescribed daily dose (PDD) toib WHO Defined L Daily Dose (DDD ) e r u t c e r L o e h t n i u l a n O by Ratio1.0 D I © M C S E DDD* Oral AMX-Enz 1g
WHO
Parenteral Ciprofloxacin DDD 0.5g
DDD* P AMX-Enz 3g
PDD 0.4gx2=0.8g Ratio 0.5/0.8=1.6
DDD* Oral Cip 1g
*DDD Defined Daily *Dosages 2006 http://www.whocc.no/atcddd/ Ansari, Erntell, Goossens, Davey CID 2009
The European Surveillance of Antimicrobial Consumption (ESAC) point prevalence survey of antibacterial use in 20 European hospitals in 2006.
y r a r Fig 2. Ratio of prescribed daily dose (PDD) toib WHO Defined L Daily Dose (DDD) e r Conclusion u t c •WHO DDDs should not be used as e r L the sole measure of antimicrobial use o e h t because of different results compared n i u l with PDDsa n O by D © I M C S E Ansari, Erntell, Goossens, Davey CID 2009
y r How to measure antimicrobial consumption a Patient level National level Outpatients (all) Hospitals (all)
r b i L e
r u t c e r L o Local level e Outpatient: Primaryn care centre th i au Hospital: ward nl •Point Prevalence Studies O by D © I M •Electronic patient records C S E examples: ECDC/ESAC, Swedish Strama
Outpatients per indication: UTI, pneumonia etc Hospital patients per indication: Ventilator associated pneumonia, CRBI etc
•Clinical Studies
ESCMID Postgraduate Education Course_Antimicrobial Stewardship_Measuring, Auditing and Improving_ESGAP_BSAC_London_2012
Point Prevalence Studies in Swedish Hospitals Strama PPS 2003-2010
45% 40%
Andel givna preparat
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Antibiotics Community Acquired Pneumonia (CAP)
50%
r u t c e r L o e h t n i u l a n O by D © I M
35% 30% 25% 20% 15% 10% 5% 0%
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PPS 2003, n=487 PPS 2004, n=497 PPS 2006, n=742 PPS 2008, n=750 PPS 2010, n=869
Point Prevalence Studies Antibiotics CAP
50%
Strama PPS 2003-2010
45%
Andel givna preparat
40% 35% 30% 25% 20% 15% 10% 5% 0%
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PPS Strengths PPS 2003, n=487 Measures antimicrobial prescribing per indications PPS 2004, n=497 Measures if the dose and dose interval of prescribed antibiotics is PPS 2006, n=742 appropriate for the indication PPS 2008, n=750 Measures if empirical treatment is appropriate related to results from PPS 2010, n=869 microbiological analysis (species and susceptibility testing)
r u t c e r L o e h t n i u l a n O by D © I M
PPS Weaknesses Time consuming Costs
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y r THANKS a r b i L Acknowledgement e r •Dominique Monnet, ECDC u t •Herman Goossens, ESAC, Belgium c •Mikael Hoffmann, NEPI, Sweden e r L o against antibiotic •Mats Erntell, Strama - Swedish strategic programme e h t resistance n i u l a n O by D © I M C S E
Email
[email protected]
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r u t c e r L o e h t n i u l a n O by D © I M
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y r Bonus material ra b i L e r u t c e r L o e h t n i u l a n O by D © I M
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Inpatient use: per patient-days or per admissions
Example N 1:
r u t c e r L o DDD/100 DDD/ 1000 e h t n i u patient -days admissions l a n General 270 - 300 O52 - 64by hospitals ID © M Psychiatry 5-8 180 - 300 C hospitals S E Čižman M, et al. Isis 2012; 11: 64-67.
Bojana Beović
How to measure outpatient y r a r use? ib • DDDs?
L e
r u t c e r L o • Packages? e h t n i u l a n O by • Prescriptions? D © I M C S E
Bojana Beović
y r Belgian case ra b i L Increased amount of e r amoxicillin and cou t c amoxiclav per package e antibiotics r (both L o represented 54% of e h t n outpatient i u antibiotic use): l a n O by Intensification of individual D © I patient M
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diamonds: DDD per 1000 inh/day circles: packages triangles: treatments
Less patients on antibiotics
Coenen S, et al. J Antimicrob Chemother 2014; 69:
Bojana Beović
y r Slovenian case a r b i L • No change in the content of packages e r u t c e and prescriptions/100 • Parallel decrease in DID, L PID, r o inh/y e h t n i u l a n O by D © I M C . S E Čižman M, unpublished
Bojana Beović
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r u t c e r L o e h t n i u l a n O by D © I M