Calculating Antimicrobial Consumption

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Calculating Antimicrobial Consumption
Educational workshops 2005

• prepared by Kieran Hand, Conor Jamieson, Wendy
  Lawson Hayley Wickens on behalf of UKCPA
  Infection Management Group
• Presenter name

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Aims of this session

• Describe a hypothetical example of a typical
  antimicrobial intervention study
• Use this as a practical illustration of the
  common pitfalls
• Put the concepts of bias and confounding into a
  clinical context
• Introduce the techniques of evaluating
  antimicrobial consumption / prescribing

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Outline

• Hypothetical landmark study
• Methods
• Results
• Bias / confounding
• Interrupted time series analysis
• Antibiotic prescribing analysis
• Defined daily doses (DDDs)
• Point prevalence

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Journal of Well-Meaning but Misguided Antibiotic
Research

• Ciprofloxacin restriction decimates MRSA
  incidence in an acute hospital setting
• St. Elsewhere Hospital
• 2005

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Methods

• Ciprofloxacin withdrawn from ward stock for
  medical wards on 5th floor
• Mandatory order form introduced for ciprofloxacin
• Microbiology approval required
• Policy implemented by ward pharmacists
• MRSA incidence measured before and after
  intervention (six months either side)

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Results primary endpoint
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Possible alternative explanations for ? MRSA and
apparent relationship to ciprofloxacin restriction
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Validating the data

• Study authors contacted
• Further data requested
• Study to be included in a meta-analysis
• Information supplied
• Staffing and activity
• Control wards
• MRSA isolates by month
• Infection control initiatives
• Antibiotic usage

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Staffing levels / activity figures

• During the intervention phase, 2/6 wards on the
  5th floor were closed due to a financial crisis
  in the trust
• Numbers of nursing staff on each open ward
  remained stable

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Results adjusted for activity
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Control for regression to mean

• As luck would have it
• The 4th floor of the hospital has similar medical
  wards to the 5th floor where the intervention
  took place
• Ciprofloxacin prescribing was not restricted on
  the 4th floor
• Can the 4th floor be used as a control?

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Results intervention (5th floor) versus control
(4th floor)
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Time series analysis withdrawal of intervention
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Interrupted time series analysis

• Examination of the data expressed as MRSA
  prevalence by month in the period prior to and
  during the intervention may shed some light on
  our findings

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Interrupted time series analysis MRSA isolates
from 5th floor
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Interrupted time series Segmented regression
analysis
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Handwashing initiatives confounding factor

• Comparing
• 5th floor (restriction handwashing) with
• 4th floor (handwashing only) with
• 3rd floor (no restriction, no handwashing
  initiatives)
• allows us to assess how much of the perceived
  effect was due to ? handwashing awareness

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Results handwashing (5th 4th floors) versus
control (3rd floor)
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Ciprofloxacin prescribing

• Evaluation of ciprofloxacin usage during the
  study will help validate any proposed
  relationship between prescribing and MRSA

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Tools of the trade measuring antimicrobial
consumption

• Cost/expenditure
• Easy but misleading e.g. price changes
• Gross usage/quantity
• More reliable but variable units (packs, grams)
• Defined daily doses (DDDs)
• WHO standardised units of usage
• DDDs/1000 bed-days
• Use adjusted for activity
• Allows comparison between hospitals

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DDDs singing from the same score

• Ciprofloxacin - WHO DDD 1.0g (oral)
• e.g. quantity per year
• 37,480 x 250mg tablets
• 9,370g
• divide by 1.0g
• 9,370 DDDs
• To account for activity, divide by occupied bed
  days/year
• divide by 328,500 occupied bed days
• 0.03 DDD per occupied bed day
• 30 DDD/1,000 occupied bed days for oral
  ciprofloxacin

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Results antibiotic usage
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Time series analysis ciprofloxacin (total DDDs)
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Time series analysis ciprofloxacin usage
adjusted for activity
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MRSA rates and ciprofloxacin usage correlation?
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Revised study conclusions !

• ?MRSA prevalence during period of intervention
  undoubtedly NOT due to restriction of
  ciprofloxacin prescribing
• Results may be explained by regression to the
  mean or successful handwashing initiatives

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Designing a better study

• Consider the factors you could change to plan
  this study in line with the principles of good
  study design

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any suggestions?
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DDD usage a pinch of salt!

• No measure of individual exposure to antibiotics
  or quality of prescribing
• Case mix and dose convention
• Relatively high usage may simply be due to higher
  doses used in local practice or sicker patients
• Relatively low usage may indicate greater
  paediatric patient case mix
• Subject to limitations of pharmacy software
  systems
• Can you separate antibiotics issued for use
  during inpatient stay from those issued for
  discharge?
• ESAC becoming more interested in point prevalence

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Admissions or Bed Days?
Filius et al, J Antimicrob Chemother 2005, 55
805-8
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Point prevalence studies

• Another approach to evaluating antibiotic
  prescribing
• Snapshot picture of prescribing
• once/twice yearly
• To study prescribing patterns
• use of restricted anti-infectives
• routes of administration (potential for IV ? PO)
• duration of use
• combinations prescribed
• indication if documented!
• To identify areas for intervention

Dean B et al. IJPharmPract 2002 10121-5
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Point prevalence studies sample data

• Data from point prevalence study in a London
  teaching hospital in 2004
• 34 of patients received 1 dose of antibiotic
• Mean 1.9 antibiotics per patient
• 16 of patients on 3 antibiotics
• Median course length 3 days
• 9 had length of course specified
• 16 of antibiotics from restricted list 6
  authorised
• 91 of antibiotics at appropriate dose
• 40 of antibiotics IV
• 70 of antibiotics judged to be an appropriate
  choice

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Take-home messages
Poor quality research
Poor quality evidence

• Wastes the time of people who conduct it
• Wastes the time of the people who read it
• Influences practice inappropriately ? worse
  outcomes for patients

Its as easy to do it right as it is to do it
wrong!