Quality Assurance of Antimicrobial Susceptibility Testing

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Quality Assurance of Antimicrobial Susceptibility
Testing

• Gunnar Kahlmeter
• Dept of Clinical microbiology, Växjö, Sweden
• The National Institute for Infectious Disease
  Control
• SRGA SRGA-M, BSAC and EUCAST

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Antimicrobial susceptibility testing is about
short-term and long-term credibility!Surprising
findings or trends will be questioned!
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Standardisation/Calibration of method
Routine quality control
Quality Assurance
Education
Expert rules
Internal Quality Assessment (specimen
reprocessing)
External Quality Assessment
Adapted from Derek Brown
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Standardisation and calibrationof method

• Standardised methodology (BSAC, CA-SFM, DIN,
  NCCLS, SRGA)
• QC-strains with target values
• Reference MIC-distributions of wild type bacteria
  (on www.eucast.org)
• Reference zone diameter distributions of wild
  type bacteria (on SRGA website and within the
  BSAC system)

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E.coli ATCC 25922
Uppdaterad 2000-04-18
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Reference MIC-distributions onwww.eucast.org
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Reference MIC-distributions onwww.eucast.org
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Reference zone diameter distributions
throughSRGA and BSAC
Data by Trevor Winstanley
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Reference zone diameter distributions through
SRGA and BSAC
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E.coli vs. gentamicin 30 µgn2478 from 17
countries
S/R 21/17
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• Discrepancies discovered in the validation
  procedure - analysis and suggested measures
• - one or more of the distributions deviate from
  what is expected (the median is off, the
  distribution is wider than expected, the part of
  the distribution that ought to be unimodal is
  bimodal, etc) the pattern of the deviation can be
  used to diagnose the problem
• are all basic parameters alike for the two
  histograms (disk strengths, additives,
  atmosphere, calibration of the CO2-incubator,
  temperature etc).
• are species-identification procedures
  equivalent?
• do the aberrations occur with media containing
  supplements? or with media or disks sensitive to
  storage? or with antibiotics sensitive to changes
  in pH (aminoglycoside, erythromycin)? or with
  antibiotics sensitive to the autoclaving of the
  medium (nitrofurantoin).

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Zone diameter distributions from 4 Swedish
laboratories illustrating different
methodological outputs.
Reference SRGA distribution
Median
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• Discrepancies discovered in the validation
  procedure - analysis and suggested measures
• If the majority of the distributions deviate from
  the expected there should be a pattern
• inhibition zones smaller than the reference
  histograms inoculum too dense or incorrect agar
  volume in the plates (depth gt4 mm).
• inhibition zones larger than the reference
  histograms incorrect agar volume in the plates
  (depth lt4 mm).

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Standardisation/Calibration of method
Routine quality control
Quality Assurance
Education
Expert rules
Internal Quality Assessment (specimen
reprocessing)
External Quality Assessment
Adapted from Derek Brown
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Routine quality control

• QC-strains with target values (target values,
  permitted range, trend analysis in Shewart
  diagrams)- general overall proficiency check-
  specific rare organisms N.gonorrhoeae,
  H.pylorii, fungi etc
• Serial analysis of zone diameter distributions
  (or MIC-distributions)

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E.coli ATCC 25922
Uppdaterad 2000-04-18
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Period of calibration
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Variation attributable to the lab.technician (the
inoculum)
One of my oldest friends but her inocula were
always a bit too dense!
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Discrepancies in results with quality control
strains - analysis and remedies Random errors
cannot be avoided but shall be controlled.
Reference strains have been assigned target
values and acceptable intervals for random
variation. Occasional deviation can be accepted
but trends and recurring patterns should be
investigated, explained and corrected.
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Discrepancies in results with quality control
strains - analysis and remedies Systematic errors
(systematic high or low values, or a trend)
should be investigated and corrected. - wrong
strain- disc content- volume of medium- pH of
medium - atmosphere and incubation
temperature)- aging of plates If this does not
explain and solve the problem the most probable
cause is the density of the inoculum.
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A change in the ion-content of ISA (Oxoid)
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Routine quality control

• QC-strains with target values (target values,
  permitted range, trend analysis in Shewart
  diagrams)- general overall proficiency check-
  specific rare organisms N.gonorrhoeae,
  H.pylorii, fungi etc
• Serial analysis of zone diameter distributions
  (or MIC-distributions)

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Internal QA Serial analysis of zone diameter
distributions
The regular analysis of zone diameter
distributions of consecutive clinical
isolates provide good internal quality
asessment median (accuracy) width
(reproducibility) shape (tells you all sorts of
things about the drug, species, lab)
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A high degree of reproducibility! A high degree
of credibility!
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Epidemic in the Lagan area
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Standardisation/Calibration of method
Routine quality control
Quality Assurance
Education
Expert rules
Internal Quality Assessment (specimen
reprocessing)
External Quality Assessment
Adapted from Derek Brown
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Expert rules are an important part of
QA Penicillin resistance does not exist in
S.pyogenes- faulty disk Ampicillin resistance
in E.faecalis is very rare- erroneous species
identification Methicillinresistance in
Staphylococci should not permit an S for other
betalactam antibiotics- dont do them youll
get it wrong! Mistrust clarithromycin S if
erythromycin R- someone got the breakpoint
wrong
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Standardisation/Calibration of method
Routine quality control
Quality Assurance
Education
Expert rules
Internal Quality Assessment (specimen
reprocessing)
External Quality Assessment
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External Quality Assessment

• The distribution of strains with known
  antimicrobial resistancies or MIC-values
• - NEQAS, EQUALIS, RING, LABKA etc
• - panel of experts to chose strains and to make
  the analysis of results and prepare comments
• The analysis of yearly distributions of the
  quantitative results of consecutive clinical
  isolates combined EQA and resistance
  surveillance.

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EQA in NEQAS and EARSS- please refer to NEQAS
and EARSS reports
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Sweden

• 100 consecutive patient isolates per bacterium
  and antibiotic and year and lab.
• Each lab enter zone diameters over internet.
• QA - the distributions are compared (median,
  width, scew) with reference.
• Resistance surveillance - using SRGA breakpoints
  the resistance frequencies calculated and
  tabulated

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S/R 18/17

• Each laboratory is asked to test 100 consecutive
  patient strains of defined species (3 - 5)
  against defined antibiotics (4 - 6).
• The zones are entered over the internet (see
  www.srga.org)
• 30 labs x 100 strains 3000 strains per species
  antibiotic year with good geographical
  distribution.

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ResNet
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