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1 Measuring antimicrobial consumption: why, what and how? 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

2 Measuring antimicrobial consumption: why, what and how? 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

3 Measuring antimicrobial consumption: why, what and how? Antibiotic consumption in humans* - Primary care (90% of human ABC) - Longterm care facilities (HUB for ABR transmission) - Hospitals: general wards - Hospitals: specialized wards, e.g. ICUs Note: Consumption in animals not included in this presentation

4 Measuring antimicrobial consumption: why, what and how? 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 Courtesy: Herman Goossens

5 Measuring antimicrobial consumption: why, what and how? National level Outpatients (all) Hospitals (all) Local level Outpatient: Primary care centre Hospital: wards Patient level Outpatients per indication: UTI, pneumonia etc Hospital patients per indication: Ventilator associated pneumonia (VAP), Catheter Related Blood stream Infection (CRBI) etc

6 Definition of Defined Daily Dose (DDD WHO ): DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults.

7 DDD per 1000 inhabitants per day Antibiotic Consumption in EU - Outpatients *DDD Defined Daily Doses per 1000 inhabitants per day H. Goossens Lancet 2005; 365:

8 DDD per 1000 inhabitants per day DDD per 1000 inhabitants per day Outpatients National Level Antibiotics consumption in Sweden, Source Apotekens Service AB, Concise J01 exkl metenamin glidande medelvärde 12 månader bakåt 0

9 DDD per 1000 inhabitants per day DDD per 1000 inhabitants per day Outpatients National Level Antibiotics consumption in Sweden, Source Apotekens Service AB, Concise Advantage of measuring J01 exkl metenamin the DDDs Easy access Low cost Not time consuming Sustainable Useful for bench marking May be used for measuring effect of interventions = Time series analysis glidande medelvärde 12 månader bakåt

10 DDD Defined Daily Dose Guided Tour on Guided Tour DDD on

11 DDD Defined Daily Dose Guided Tour on 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. 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. 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. 11

12 DDD Defined Daily Dose Guided Tour on 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. 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. Anatomical Therapeutic Chemical (ATC) classification for medicines 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. 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. 12

13 DDD Defined Daily Dose Guided Tour on 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. 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. 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. 13

14 DDD Defined Daily Dose Guided Tour on Last updated: defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose.

15 DDD WHO DDD Defined Daily Dose Guided Tour on ORAL DDD WHO (1g ciprofloxacin) PARENTERAL DDD WHO (0.5g ciprofloxacin) defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose.

16 DDD WHO DDD Defined Daily Dose Guided Tour on ORAL DDD WHO (1g ciprofloxacin) PARENTERAL DDD WHO (0.5g ciprofloxacin) 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) defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose.

17 DDD WHO DDD Defined Daily Dose Guided Tour on ORAL DDD WHO (1g ciprofloxacin) PARENTERAL DDD WHO (0.5g ciprofloxacin) 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) defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Parenteral ciproflox. PDD 0.8g DDD WHO 0.5g

18 DDD WHO DDD Defined Daily Dose Guided Tour on ORAL DDD WHO (1g ciprofloxacin) PARENTERAL DDD WHO (0.5g ciprofloxacin) Most common precribed daily dose ORAL Tabl. Ciprofloxacin 0.5g x 2 (1g/24h) BUT PARENTERAL Inf Ciprofloxacin 0.4g x 2, i.v. defined daily dose is a unit of measurement and does not necessarily reflect the recommended or Prescribed Daily Dose. Parenteral ciproflox. PDD 0.8g DDD WHO 0.5g = 1.6 (correction factor) to convert. DDD WHO to PDD

19 DDD and Denominators 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. 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.

20 DDD per 1000 inhabitants per day Outpatients National Level Antibiotics consumption in Sweden, DDD per 1000 inhabitants per day, Source : Apoteket AB Strama campaign rational use

21 DDD per 1000 inhabitants per day Outpatients National Level Antibiotics consumption in Sweden, DDD per 1000 inhabitants per day, Source : Apoteket AB DDD/1000 inh./day were used for measuring effect of the interventions (time series analysis) Strama campaign rational use

22 HOSPITAL

23 DDD per 1000 inhabitants per day J01 exkl metenamin DDD per 1000 inhabitants per day Antibiotic consumption in Swedish Hospitals Trends Source Apotekens Service AB, Concise

24 DDD per 1000 inhabitants per day J01 exkl metenamin DDD per 1000 inhabitants per day Antibiotics consumption in Swedish Hospitals Strama campaign, Trends rational use Source Apotekens Service AB, Concise

25 DDD per 1000 inhabitants per day overestimation 0.8 of increased consumption Explanations/Errors (PDDs) Antibiotics consumption in Swedish Hospitals Strama campaign, Trends rational use Source Apotekens Service AB, Concise 0.2 sepsis/septic shock DDD per 1000 inhabitants per day Our analysis based on point prevalence studies showed an J01 exkl metenamin 1.New mix of drugs with lower DDDs than prescribed daily doses 2.Increased prescribed daily doses (PDDs) to save lifes in severe 3.Increased prescribed daily doses (PDDs) to reduce emergence 0 of resistance

26 DDD per 1000 inhabitants per day Useful 0.8 for bench marking stewardship 0.6 = Time series analysis but be aware of DDD per 1000 inhabitants per day Antibiotics consumption in Swedish Hospitals Strama campaign, Trends rational use Source Apotekens Service AB, Concise Advantage of measuring the DDDs in hospitals May be used for measuring effect of antibiotic errors J01 exkl metenamin

27 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 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

28 Inpatient use: per patient-days or per admission? The Dutch University Hospitals 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:

29 Inpatient use: per patient-days or per admission? The Dutch University Hospitals What does the intensification of antibiotic treatment in hospitals mean for the antimicrobial resistance?! 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:

30 Benchmarking inpatient antibiotic use: does the number of hospital beds matter? The Dutch hospitals (2009): 69.8 DDD/100 patient-days The French hospitals (2007): 41.1 DDD/100 patient-days The Dutch inpatient antibiotic consumption (2011): 0.97 DDD/TID The French inpatient consumption (2011 ): 2.02 DDD/TID (+208%)? Hospital beds per 100,000 Inh (2009): France: (+ 43%) The Netherlands: Amadeo B, et al. J Antimicrob Chemother 2011; 66: Kwint HM, et al. J Antimicrob Chemother 2012; 67:

31 Number of antibiotic prescriptions or recipe/1000 inh./year

32 Prescriptions/1000 inhabitants/year Number of antibiotic prescriptions (or recipe) /1000 inhabitants/year Antibiotic consumption (J01 exkl methenamine) in different age groups Community care in Sweden , prescriptions per 1000 inhabitants and year Data source: The National Board of Heatlh and Welfare and The National Corp. of Swedish Pharacies Strama strated with Intervention - Rational use - no AB for viral inf. 0-4 years 5-14 years years years 0

33 Change in antibiotic prescriptions (or recipe)/1000 inhabitants/year Ages 0-4, 5-14, 15-64, 65- (all Swedish recipe) -70 % -58 % Source: Mats Erntell

34 Change ( ) in antibiotic prescriptions (or recipe)/1000 inhabitants/year Ages 0-4, 5-14, 15-64, 65- (all Swedish recipe) -70 % Reimbursement to counties decreasing prescriptions (approx EUR/year) -58 % Source: Mats Erntell

35 Prescribed daily dose (PDD) Data source Electronic system Point Prevalence studies (PPS) Charts retrospectively

36 Prescribed Daily Doses (PDDs) Defined locally (hospital, ward) or within a group of hospitals PDD = average prescribed dose on the main indication (in a hospital, ward or group of hospitals) Grams (or I.U.) active substance Do NOT allow inter-hospital comparisons! No. PDDs = No. packages x No. tablets per package x No. g per tablet PDD of antimicrobial in grams

37 The European Surveillance of Antimicrobial Consumption (ESAC) point prevalence survey of antibacterial use in 20 European hospitals in Fig 2. Ratio of prescribed daily dose (PDD) to WHO Defined Daily Dose (DDD WHO ) DDD* Oral AMX-Enz 1g DDD* P AMX-Enz 3g DDD* Oral Cip 1g Parenteral Ciprofloxacin DDD 0.5g PDD 0.4gx2=0.8g Ratio 0.5/0.8=1.6 Ratio1.0 *DDD Defined Daily * Dosages Ansari, Erntell, Goossens, Davey CID 2009

38 The European Surveillance of Antimicrobial Consumption (ESAC) point prevalence survey of antibacterial use in 20 European hospitals in Fig 2. Ratio of prescribed daily dose (PDD) to WHO Defined Daily Dose (DDD) Conclusion WHO DDDs should not be used as the sole measure of antimicrobial use because of different results compared with PDDs Ansari, Erntell, Goossens, Davey CID 2009

39 How to measure antimicrobial consumption National level Outpatients (all) Hospitals (all) Local level Outpatient: Primary care centre Hospital: ward Point Prevalence Studies examples: ECDC/ESAC, Swedish Strama Electronic patient records Outpatients per indication: UTI, pneumonia etc Hospital patients per indication: Ventilator associated pneumonia, CRBI etc Clinical Studies Patient level ESCMID Postgraduate Education Course_Antimicrobial Stewardship_Measuring, Auditing and Improving_ESGAP_BSAC_London_2012

40 Andel givna preparat 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Point Prevalence Studies in Swedish Hospitals Antibiotics Community Acquired Pneumonia (CAP) Strama PPS PPS 2003, n=487 PPS 2004, n=497 PPS 2006, n=742 PPS 2008, n=750 PPS 2010, n=869

41 Andel givna preparat 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Point Prevalence Studies Antibiotics CAP Strama PPS 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 PPS 2010, n=869 from microbiological analysis (species and susceptibility testing) PPS Weaknesses Time consuming Costs

42 THANKS Acknowledgement Dominique Monnet, ECDC Herman Goossens, ESAC, Belgium Mikael Hoffmann, NEPI, Sweden Mats Erntell, Strama - Swedish strategic programme against antibiotic resistance Hakan.Hanberger@liu.se

43

44 Bonus material

45 Inpatient use: per patient-days or per admissions Example N 1: General hospitals Psychiatry hospitals DDD/100 patient -days DDD/ 1000 admissions Čižman M, et al. Isis 2012; 11: Bojana Beović

46 How to measure outpatient DDDs? Packages? Prescriptions? use? Bojana Beović

47 Coenen S, et al. J Antimicrob Chemother 2014; 69: Bojana Beović diamonds: DDD per 1000 inh/day circles: packages triangles: treatments Belgian case Increased amount of amoxicillin and coamoxiclav per package (both antibiotics represented 54% of outpatient antibiotic use): Intensification of individual patient Less patients on antibiotics

48 Slovenian case No change in the content of packages Parallel decrease in DID, PID, and prescriptions/100 inh/y Čižman M, unpublished. Bojana Beović

49

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