Quality Control and Quality Assurance for Antibiotic Testing

26 Sep 2013 Microbiology Technical Workshop Lily Ng Siew Yong

Quality assurance

practice of assessing performance in all steps of the process to promote excellent outcome in medical care

Quality control aggregate of processes and techniques to detect, reduce, and correct deficiencies in an analytical process.

Processes

Quality Assurance
With thanks to Derek Brown @ EUCAST Educational Workshop: 31 March 2012

Standard documentation Routine Quality Control External Quality Assurance

Quality
Evaluation Internal Quality Assurance

Validation

Education & Training

External quality assurance

The challenge of laboratory procedures with specimens of known but undisclosed content
External laboratory Or organization
Prepares sample and sends to participants Receives and analyses results Prepares report

Participating laboratory
Receives sample and performs testing Reports results

Analyses reports & deficiencies Institutes corrective actions

EQA
Examples of EQA organizations College of American Pathologists Royal College of Pathologists (Australasia) UKNEQAS Local reference laboratories

EQA: benefits
Independent assessment of performance Assessment of performance over time Comparison with other laboratories Highlights problem areas Performance related to guidelines and methods

EQA: benefits
International differences highlighted Gives practical experience of difficult tests (especially if resistance is uncommon) Provides background information and guidance on appropriate methods Performance indicator for accreditation

EQA: limitations
Number of specimens distributed is small May be considered inappropriate to send some organisms Specimens do not reflect routine isolates Laboratories may not treat specimens as routine

EQA: @ CGH Laboratory

Survey subscription based on services offered Survey sample management Result submission management Performance assessment

Internal Quality Assurance

The challenge of laboratory procedures by repeat testing of specimens of unknown content
Sample
blinded routine testing results routine testing results

reported

compare & evaluate

Internal Quality Assurance

The challenge of laboratory procedures by repeat testing of specimens of unknown content
Sample
blinded routine testing results routine testing results routine testing results

Sample
blinded routine testing results

reported

compare & evaluate

reported

compare & evaluate

Internal Quality Assurance

The challenge of laboratory procedures with spiked specimens
Spiked sample
Routine testing

results

reported

Compare & evaluate

IQA: Benefits
Check of laboratory processes Identifies: typographical errors Inconsistencies between different technologists process errors

IQA: Practical issues

Different organisms picked from mixture on primary plates Borderline susceptibility leads to variation Discrepancies with difficult tests Labor intensive Sample variability (stored samples)

IQA: @ CGH Laboratory

Target: 50 specimens issued monthly Frequent issues: Variation in zone diameters Enumeration of cells Urine viable count

Audit
Processes Documentation Skills Knowledge

check - inspect - verify

Audit: @ CGH Laboratory

Accreditation audit Internal surveillance Target 10 % of total test specimens July 2013: 1,198 of 13,209 specimens Frequent issues: Variation in zone diameters Enumeration of cells Urine viable count

Audit: @ CGH Laboratory

Errors Internal surveillance 10 % of total test specimens July statistics: 1,198 of 13,209 specimens

Documentation
Standard operating procedures
us er-friendly, not reference text! updated regularly document control

Examples from:
WHO SOP (SE Asia) http://apps.searo.who.int/PDS_DOCS/B0217.pdf HPA (UK) SOP repository http://www.hpa.org.uk/SMI Mount Sinai SOP http://microbiology.mtsinai.on.ca/manual/anti/ind ex.shtml

Readily accessible

Documentation
Standard operating procedures
us er-friendly, not reference text! updated regularly document control

Examples from:
http://apps.searo.who.int/PDS_DOCS/B0217.pd f http://www.hpa.org.uk/SMI

Readily accessible

Documentation
Standard operating procedures
us er-friendly, not reference text! updated regularly document control

Readily accessible
hard copy s oft copy

Evaluation & Validation

For new testing methods / antibiotics introduced into laboratory
Analytic accuracy Precis ion Compare new against gold s tandard Repeatibility

Evaluation & Validation @ CGH Laboratory

Introducing use of yeast AST testing by Vitek
Compare results obtained by Vitek agains t reference microbroth dilution method us ing a range of various s pecies 20 cons ecutive days of parallel testing

Analytic accuracy

Precis ion

www.hpa.org.uk/webc/hpawebfile/h paweb_c/1317131674973

Education & Training

Competency
Define skills to be assessed Define how to assess Define who will assess Documentation Remediation

Continuing professional education Skills upgrading

Reference Competency Assessment in the Clinical Microbiology Laboratory. Clin. Microbiol. Rev. July 2004 vol. 17 no. 3, 681-694

Training topics Importance of proper technique for AST Observation of resistance mechanisms expression in Proteuses Lab reports vs clinical impact of Staphylococcal AST Interpretation and reporting of test results for Enterococcal AST

Antimicrobials and the beta lactam family drug Interpretation and reporting of test results for family Enterobacteriaceae AST Extended spectrum beta lactamases Staph lugdunensis : significance, identification, and susceptibility ampC beta lactamases Interpretation and reporting of test results for non-Enterobacteriaceae ASTcs Identification, susceptibility testing and result interpretation of Strep pneumoniae MIC determination by macrobroth and microbroth methods Microscan testing Drug options, result interpretation and reporting for Staphylococcal AST

Penicillin binding proteins in relation to staphylococcal growth and drug resistance Antimicrobial testing and reading of test findings

Education & Training @ CGH Laboratory

Microbiology Training Record
Date
12/03/2013 26/03/2013

Training Category
Talk Practical

Topic
Importance of proper technique for AST

Trainer
LN G LN G H J / LN G H J / LN G LN G H J / LN G LN G

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ELC

H YX

HJ

SM F LH Z TSY

SFM NAP OJL

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Observation of resistance machanisms expression in Proteuses Antimicrobials and the beta lactam family 11/04/2013 Powerpoint drug family 17/04/2013 Powerpoint Extended spectrum beta lactamases 22/04/2013 Talk Staph lugdunensis: significance, identification, and susceptibility

Trai n e r

Trai n e r

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24/04/2013 Powerpoint ampC beta lactamases 29/05/2013 Talk Penicillin binding proteins in relation to staphylococcal growth and drug resistance Antimicrobial testing and reading of test findings Drug options, result interpretation and reporting for Staphylococcal AST
(incl FOX vs OX, E vs CC, Quinolones )

Trai n e r

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30/05/2013 Powerpoint 11/06/2013 Talk, part 1

Insert page of CME AST listing here

H J / LN G 0.5
Trai n e r P

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LN G

0.5

Sp e ake r

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11/06/2013 Talk, part 2

Lab reports vs clinical impact of Staphylococcal AST

(incl TG C, RA5, FU , G m, SXT)

LN G

0.5

Sp e ake r

AL

Quality Control

Antibiotic testing
Temperature Atmosphere

Disc potency Media Organism

QC: Antibiotic testing

Specified routine quality control strains are used to monitor test performance Quality control strains must be from a reliable source Proper storage to maintain characteristics

QC Strains: specific tests

QC Disc: acceptable ranges

Acceptable range for ATCC strains

QC Disc: acceptable ranges

QC Disc: testing

Westgard rules
multiple rules used to monitor a charted process determines if the process is within acceptable limits

Westgard relevant
10x reject when 10 consecutive control measurements fall on one side of the mean.

QC Disc: monitoring

QC Disc: failures
Cause found: repeat x 01 ID cause No obvious cause 5 consecutive days Re-examine 1 out of range Repeat out of range Repeat ok = case close All within range = case close repeat

Antibiotic testing: Common sources of error

Media
pH Thickness Storage Contamination Wrong media

QC strains
Wrong s trains Inocula Storage Contamination Age

Antibiotics
Storage Wrong disc

Procedures
Incubation conditions Dis c placement trans cription

Antibiotic testing: Common sources of error

Media
Storage Thickness Contamination pH Wrong media

QC strains
Wrong s trains Inocula Storage Contamination Age

Antibiotics
Storage Wrong disc

Procedures
Incubation conditions Dis c placement trans cription

Antibiotic testing: Common sources of error

Media
Storage Thickness Contamination pH Wrong media

QC strains
Age Storage Inocula Contamination Wrong s trains

Antibiotics
Storage Wrong disc

Procedures
Incubation conditions Dis c placement trans cription

Antibiotic testing: Common sources of error

Media
Storage Thickness Contamination pH Wrong media

QC strains
Wrong s trains Inocula Storage Contamination Age

Antibiotics
Storage Wrong disc

Procedures
Dis c placement Incubation condition trans cription

QC Disc: Troubleshooting

QC of Automated Systems
Use the recommended quality control strains Follow manufacturers instructions Purity check of used inocula

Restricted range of test concentrations means that the available range may not include the MIC of the control strain.

Quality Assurance

Some concluding thoughts

Quality measure Clinically relevant testing strategies Tes ting of reference QC s trains Technical competency Organis m antibiogram verification Supervis or review of results Procedure manual Cumulative antibiogram Proficiency s urveys Other

Effort (%) 15 15 15 15 15 10 5 5 5

Rankin I. D. (2005). Quality Assurance/Quality Control (QA/QC) In: Coyle M. B. (ed.) Manual of Antimicrobial Susceptibility T esting. 1st ed, Washington, D.C.: American Society for Microbiology; 63-89.

Conclusion

Can we afford quality as s urance in microbiology laboratories?

15% of Microbiology reports are wrong!

Journal of Hospital Infection. V ol 30, Supp, June 1995, Pages 364371

Can we afford NOT TO HAVE quality as s urance in microbiology laboratories?

Resources
WHO Laboratory Quality Management System Handbook 2011
http://whqlibdoc.who.int/publications/2011/9789241548274_eng.pdf

CLSI M40 susceptibility testing

www.clsi.org

EUCAST quality tables

www. eucast.org/antimicrobial_susceptibility_testing/qc_ tables/

General Review
http://www.intechopen.com/books/latest-research-into-qualitycontrol/quality-assurance-in-antimicrobial-s usceptibility-testing#B23