EARS-Net EQA 2014. Derek Brown (UK)

ECDC EARS-Net External Quality Assessment

(EQA) 2014

Derek Brown Peterborough (UK)

EUCAST Scientific Secretary UK NEQAS Antimicrobial Susceptibility Testing Specialist Advisory Group

Christine Walton and Shila Seaton

UK NEQAS for Microbiology, Colindale, London (UK)

UK NEQAS

Objectives of EARS-Net External Quality Assessment

• To assess the accuracy of antimicrobial

susceptibility test results reported by laboratories

• To assess the comparability of routine antimicrobial susceptibility test results between laboratories and countries

• Education

Participation in EARS-Net EQA

2014 2013 2012 2011 2010

Countries 31 30 30 31 31

Laboratories 905 872 880 911 873

Laboratories responding 93% 92% 92% 90% 88%

Guidelines used in EARS-Net EQA 2014

0

10

20

30

40

50

60

70

80

90

AT BE BG CY CZ DE DK EE ES FI FR GR HR HU IE IS IT LT LU LV MT NL NO PL PT RO SE SI SK UK

EUCAST CLSI DIN SFM BSAC

Country

No.

of p

artic

ipan

ts

Trends in antimicrobial susceptibility testing guidelines in EARS-Net

0

10

20

30

40

50

60

70

80

90

2010 2011 2012 2013 2014

Perc

ent p

artic

ipan

ts

CLSI

All EUCAST

EUCAST

EUCAST-based

Methods use in EARS-Net EQA 2014

Guideline Automated Disk MIC OTHER Total % guideline

BSAC 2 9 0 2 13 1.5

DIN 0 0 1 0 1 0.1

EUCAST 312 239 51 3 605 72.2

CLSI 100 58 6 0 164 19.6

SFM 20 35 0 0 55 6.6

Total 434 341 58 5 838 100

% method 51.8 40.7 6.9 0.6 100

Escherichia coli specimen 2486 CTX-M-15 ESBL

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI Amoxicillin ≥128 R R Ampicillin ≥128 R R Cefotaxime ≥128 R R Ceftazidime 32-64 R R Ceftriaxone ≥128 R R Amoxicillin-clavulanic acid ≥128 (64) R R Piperacillin-tazobactam 32-64 R I Imipenem 0.12-0.25 S S Meropenem 0.03 S S Doripenem S S Ertapenem 0.12-0.25 S S Ciprofloxacin ≥128 R R Gentamicin ≥128 R R Tobramycin ≥128 R R Amikacin 16 I S

0

20

40

60

80

100

% C

onco

rdan

ce

Antimicrobial agent

Escherichia coli specimen 2486

Escherichia coli specimen 2486

Amoxicillin-clavulanic acid resistant MICs ≥ 128 mg/L (fixed 2 mg/L clavulanic acid)

64 mg/L (2:1 ratio amox:clav)

EUCAST breakpoints S ≤8, R >8 mg/L (fixed clav 2 mg/L)

CLSI breakpoints S ≤8, R ≥ 32 mg/L (2:1 ratio amox:clav)

• Tendency to reporting intermediate with CLSI method

Guideline n %S %I %R EUCAST 623 1.1 2.7 96.1 CLSI 166 2.4 27.1 70.5

Escherichia coli specimen 2486 Piperacillin-tazobactam MICs 32-64 mg/L EUCAST resistant ( breakpoints S ≤8, R >16 mg/L) CLSI intermediate (breakpoints S ≤16, R ≥ 128 mg/L) • High discrepancy rate in reporting with all guidelines

• High discrepancy rate with all methods

Guideline n %S %I %R EUCAST 646 38.9 28.5 32.6 CLSI 163 59.5 28.2 12.3

Guideline, method n %S %I %R EUCAST, disk diffusion 274 27.4 38.3 34.3 EUCAST, automated 322 48.1 20.2 31.7 CLSI, disk diffusion 55 63.6 29.1 7.3 CLSI, automated 98 58.2 26.5 15.3

Escherichia coli specimen 2486 Amikacin MIC 16 mg/L EUCAST intermediate ( breakpoints S ≤8, R >16 mg/L) CLSI susceptible (breakpoints S ≤16, R ≥ 64 mg/L) • High discrepancy rate in reporting with all guidelines, partly

in line with breakpoints

Guideline n %S %I %R EUCAST 579 56.8 38.7 4.5 CLSI 153 80.4 17.0 2.6

Escherichia coli specimen 2486 Amikacin MIC 16 mg/L EUCAST intermediate ( breakpoints S ≤8, R >16 mg/L) CLSI susceptible (breakpoints S ≤16, R ≥ 64 mg/L) • With EUCAST guidelines more discrepancies with disk

diffusion method

Guideline, method n %S %I %R EUCAST, disk diffusion 242 80.6 16.9 2.5 EUCAST, automated 282 34.0 61.4 4.6 CLSI, disk diffusion 56 83.9 10.7 5.4 CLSI, automated 91 78.0 19.8 2.2

Klebsiella pneumoniae specimen 2487 VIM carbapenemase

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI Amoxicillin ≥128 R R Ampicillin ≥128 R R Cefotaxime ≥128 R R Ceftazidime ≥128 R R Ceftriaxone ≥128 R R Amoxicillin-clavulanic acid ≥128 (64) R R Piperacillin-tazobactam ≥128 R R Imipenem 64 R R Meropenem ≥128 R R Doripenem R R Ertapenem ≥128 R R Ciprofloxacin ≥128 R R Gentamicin 1 S S Tobramycin 16 R R Amikacin 16 I S

0

20

40

60

80

100

%C

onco

rdan

ce

Antimicrobial agent

Klebsiella pneumoniae specimen 2487

Klebsiella pneumoniae specimen 2487 Amikacin MIC 16 mg/L

Aminoglycoside susceptibility was typical for an organism producing AAC(6')I, i.e. Gentamicin susceptible (MIC 1 mg/L) Tobramycin resistant (MIC 16 mg/L) Amikacin borderline (MIC 16 mg/L) EUCAST intermediate (breakpoints S ≤8, R >16 mg/L) CLSI susceptible (breakpoints S ≤16, R ≥ 64 mg/L) • High discrepancy rate in reporting with all guidelines,

partly in line with breakpoints

Guideline n %S %I %R EUCAST 590 8.0 62.3 28.8 CLSI 156 33.3 48.7 18.0

Klebsiella pneumoniae specimen 2487 Amikacin MIC 16 mg/L

• More discrepancies with disk diffusion method

• EUCAST expert rule note that acquired AAC(6')I may not confer phenotypic resistance to amikacin despite modification of amikacin, and that such organisms should be reported intermediate even if they appear susceptible. Some participants may have edited S test results to I.

Guideline, method n %S %I %R EUCAST, disk diffusion 246 13.4 53.7 32.9 EUCAST, automated 289 3.5 73.7 22.8 CLSI, disk diffusion 56 23.2 44.6 32.1 CLSI, automated 94 38.3 51.1 10.6

Staphylococcus aureus specimen 2489 VISA

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI

Penicillin 64 R R Cefoxitin ≥128 R R Oxacillin ≥128 R R Vancomycin 4 R I Teicoplanin 8-16 R S/I Erythromycin ≥128 R R Clindamycin ≥128 R R Gentamicin 128 – 256 R R Fusidic acid 0.06 - 0.12 S - Ciprofloxacin 16 R R Rifampicin ≥128 R R Tetracycline 64 R R

0

20

40

60

80

100

%C

ondo

rdan

ce

Antimicrobial agents

Staphylococcus aureus specimen 2489

Staphylococcus aureus specimen 2489 Vancomycin resistance MIC 4 mg/L

EUCAST resistant ( breakpoints S ≤ 2, R > 2 mg/L) CLSI intermediate (breakpoints S ≤ 2, R ≥ 16 mg/L)

• High error rate in reporting with all guidelines

Guideline n %S %I %R EUCAST 655 45.8 2.4 51.8 CLSI 164 57.3 39.0 3.7

Staphylococcus aureus specimen 2489 Vancomycin resistance • No testing method was reliable • Disk diffusion should not be used

Method n % reporting S

Disk diffusion only 16 87.5 MIC 370 41.4 Automated 430 50.5

Staphylococcus aureus specimen 2489 Teicoplanin resistance MIC 8-16 mg/L EUCAST resistant ( breakpoints S ≤ 2, R >2 mg/L) CLSI susceptible/intermediate (breakpoints S ≤8, R ≥32 mg/L)

• Reporting in line with guidelines

Guideline n %S %I %R EUCAST 573 7.2 1.0 91.8 CLSI 147 47.0 43.5 9.5

Streptococcus pneumoniae specimen 2489 Penicillin “intermediate”

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI

Oxacillin screen R R

Penicillin: meningitis pneumonia

0.25 – 0.5 I R S

R S

Cefotaxime meningitis pneumonia

0.06 -0.12 S S

S S

Ceftriaxone meningitis pneumonia

0.12 – 0.25 S S

S S

Levofloxacin 1 S S Moxifloxacin 0.12 S S Norfloxacin S S Erythromycin ≥128 R R Clindamycin R R

0

20

40

60

80

100

%C

onco

rdan

ce

Antimicrobial agents

Streptococcus pneumoniae specimen 1378

Streptococcus pneumoniae specimen 2489

Benzylpenicillin MIC 0.25 – 0.5 mg/L Oxacillin screen resistant • No intermediate category • Reference zone diameter 12mm

Guideline n %S %I %R EUCAST 403 8.9 5.0 86.1 CLSI 84 7.1 2.4 90.5

Streptococcus pneumoniae specimen 2489 Penicillin “intermediate” (MIC 0.25 – 0.5 mg/L) Site of infection unspecified • Breakpoints for isolates other than meningitis EUCAST S ≤0.06 R >2 mg/L CLSI (parenteral) S ≤2 R ≥8 mg/L CLSI (oral) S ≤0.06 R ≥2 mg/L • Meningitis isolate EUCAST S ≤0.06 R >0.06 mg/L CLSI S ≤0.06 R ≥0.12 mg/L Guideline n %S %I %R EUCAST 563 17.4 75.5 7.1 CLSI 116 46.5 45.7 7.8

Streptococcus pneumoniae specimen 2489 Penicillin MIC 0.25 – 0.5 mg/L • Pneumonia isolate With EUCAST breakpoints for higher doses used in

pneumonia, and CLSI parenteral breakpoints for non-meningitis isolates, expected result “Susceptible”

Guideline n %S %I %R EUCAST 627 49.9 47.2 2.9 CLSI 156 86.5 13.5 0

Streptococcus pneumoniae specimen 2489 Penicillin MIC 0.25 – 0.5 mg/L • Meningitis isolate EUCAST S ≤0.06 R >0.06 mg/L CLSI S ≤0.06 R ≥0.12 mg/L

Guideline n %S %I %R EUCAST 625 3.7 2.4 93.9 CLSI 156 3.8 1.3 94.9

Streptococcus pneumoniae specimen 2489

Norfloxacin screen EUCAST susceptible, CLSI no screening test

Guideline n %S %I %R EUCAST 265 88.7 0 11.3 CLSI 24 83.3 0 16.7

Enterococcus faecium specimen 2490 High-level gentamicin resistant

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI

Ampicillin 32-64 R R

Amoxicillin 32 R R

Teicoplanin 1 S S

Vancomycin 1 S S

High-level gentamicin resistance ≥512 HLGR HLGR

0

20

40

60

80

100

% C

onco

rdan

ce

Antimicrobial agent

Enterococcus faecium specimen 2490

Enterococcus faecium specimen 2490 High-level gentamicin resistance positive

MIC ≥512 mg/L, EUCAST HLGR >128 mg/L, CLSI >512 mg/L • Differences between guidelines

– EUCAST-based 92.7% positive, 7.3% negative – CLSI 82.6% positive, 17.4% negative

• Differences between methods – Disk 88.2% HLGR-positive – Automated 92.2% HLGR positive

• Reasons for incorrect reports of HLGR-negative? – Unstable resistance? Unlikely – Misunderstanding of report form?

Acinetobacter baumannii specimen 2491 (GES-2 carbapenemase)

Antimicrobial agent Reference MIC (mg/L) EUCAST CLSI

Amikacin ≥128 R R

Gentamicin 32-64 R R

Tobramycin 32 R R

Ciprofloxacin 64 R R

Colistin 0.5-1 S S

Imipenem 32-64 R R

Meropenem 64-≥128 R R

Doripenem R R

0

20

40

60

80

100

%C

ondo

rdan

ce

Antimicrobial agent

Acinetobacter baumannii specimen 2491

Acinetobacter baumannii specimen 2491 Aminoglycoside resistant Non-resistant reports more common with CLSI breakpoints:

Gentamicin (MIC 32-64 mg/L) Tobramycin (MIC 32-64 mg/L) Amikacin (MIC ≥128 mg/L)

Guideline S (mg/L) R (mg/L n %S %I %R EUCAST ≤4 >4 640 5.6 0.5 93.9

CLSI ≤4 ≥16 162 8.0 37.7 54.3

Guideline S (mg/L) R (mg/L n %S %I %R EUCAST ≤4 >4 544 6.4 0.3 93.3

CLSI ≤4 ≥16 131 16.0 29.8 54.2

Guideline S (mg/L) R (mg/L n %S %I %R EUCAST ≤8 >16 549 0.5 9.1 90.4

CLSI ≤16 ≥64 146 8.9 10.3 80.8

Acinetobacter baumannii specimen 2491 Aminoglycoside resistant Non-resistant reports more common with automated methods than with disk diffusion:

Gentamicin EUCAST CLSI

Guideline n %S %I %R Disk diffusion 259 2.7 0.3 99.9

Automated 322 7.8 0.6 91.6

Guideline n %S %I %R Disk diffusion 54 3.7 25.9 70.4

Automated 100 10.0 46.0 44.0

Acinetobacter baumannii specimen 2491 Aminoglycoside resistant Non-resistant reports more common with automated methods than with disk diffusion:

Tobramycin EUCAST CLSI

Guideline n %S %I %R Disk diffusion 221 3.2 0 96.8

Automated 272 9.6 0.7 89.7

Guideline n %S %I %R Disk diffusion 46 6.5 17.4 77.1

Automated 80 21.2 38.8 40.0

Acinetobacter baumannii specimen 2491 Aminoglycoside resistant Non-resistant reports more common with automated methods than with disk diffusion:

Amikacin EUCAST CLSI

Guideline n %S %I %R Disk diffusion 246 0.8 2.0 97.2

Automated 249 0.4 17.3 82.3

Guideline n %S %I %R Disk diffusion 55 3.6 7.2 89.9

Automated 84 13.1 13.1 73.8

Conclusions 2014

• Performance good for most organism-agent combinations

• Discrepancies more common when: – Susceptibility borderline – Critical differences between guidelines – Failure to follow breakpoint guidelines – Guidelines permit variable reporting – (Failure to follow method guidelines)

Many thanks to all laboratories and national distributors

UK NEQAS