Upload
harva
View
58
Download
0
Tags:
Embed Size (px)
DESCRIPTION
Susceptibility testing for Vancomycin in S. aureus : What do we do now?. 14 th March 2013. Robin A Howe. Susceptibility testing for Vancomycin in S. aureus : What do we do now?. History What are we aiming to identify? Testing issues Current recommendations. 1997: VISA - PowerPoint PPT Presentation
Citation preview
Antimicrobial use in Primary Care
Susceptibility testing for Vancomycin in S. aureus : What do we do now?
14th March 2013
Robin A Howe
Susceptibility testing for Vancomycin in S. aureus : What do we do now?• History
• What are we aiming to identify?
• Testing issues
• Current recommendations
• 1997: VISA– Mu50 Vanc MIC 8mg/L
• 2001: SARV (S. aureus with Reduced susceptibility to Vancomycin)– MIC 4mg/L– Associated with mortality in Case-control study
• 2003: VRSA– High-level resistance (>32mg/L) due to acquisition of vanA– Remains v rare
VANCOMYCIN MIC (mg/L) 1 2 4 8 16 32
CLSI (OLD) VSSA VISA VRSA BSAC/EUCAST (OLD) VSSA VRSA CLSI (NEW) VSSA VISA VRSA BSAC/EUCAST (NEW) VSSA VRSA
Hiramatsu et al. (1997) JAC 40: 135Fridkin et al. 41st ICAAC (2001)
• 1997: hetero-VISA– Mu3 Vanc MIC 2-4mg/L but population able to
grow in higher vanc concentrations
Hiramatsu et al (1997) Lancet 350: 1670
0 1 2 3 4 5 6 7 810 2
10 3
10 4
10 5
10 6
10 7
10 8
10 9
10 10
Mu 3
Mu50
MSSA
MRSA
Vancomycin (mg/L)
Col
ony
Cou
nt (c
fu/m
L)– Numerous case reports associating hVISA with treatment failure (lack of systematic studies)
Is there an association between high MICs below BP and poor outcome?
• Meta-analysis• high-VMIC
– VMIC >1 mg/L but ≤2 mg/L)
• 33 studies identified
Mavros et al. (2012) IJAA. 40: 496Mortality
Is there an association between high MICs below BP and poor outcome?
• Meta-analysis• high-VMIC
– ≥1 mg/l by BMD– ≥1.5 mg/l by Etest
• 20 studies identified
Jacob et al. (2013) IJID. 17: e93
Treatment failure
What should we aim to identify?
• Vanc MIC >2mg/L (ie BP)• ?Vanc MIC ≥1.5mg/L
– Caution about method• ?hVISA
– PAP analysis can help to define
resistance
Wootton et al (2005) AAC 49(9): 3982
What should we aim to identify?
• Vanc MIC >2mg/L (ie BP)• ?Vanc MIC ≥1.5mg/L
– Caution about method• ?hVISA
– PAP analysis can help to define
resistance
Wootton et al (2005) AAC 49(9): 3982
Pennsylvania VRSA(vanA +ve)MIC 32 mg/L
Tenover et al. AAC (2004) 48: 275.
Disc testing
14 VSSA 49 hVISA20 VISA tested by disc
Vancomycin 5 MHA
0
10
20
30
40
50
60
70
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Zone Diameter (mm)
Freq
uenc
y
V5 (VISA)
V5 (hVISA)
V5 (VSSA)
Vancomycin 5 ISO
0
10
20
30
40
50
60
70
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Zone Diameter (mm)
Freq
uenc
y V5 (VISA)
V5 (hVISA)
V5 (VSSA)
Vancomycin 30 MHA
0
10
20
30
40
50
60
70
17 18 19 20 21 22 23 24 25
Zone Diameter (mm)
Freq
uenc
y
V30 (VISA)
V30 (hVISA)
V30 (VSSA)
Vancomycin 30 ISO
0
10
20
30
40
50
60
70
18 19 20 21 22 23 24 25 26 27
Zone Diameter (mm)
Freq
uenc
y
V30 (VISA)
V30 (hVISA)
V30 (VSSA)
Davies LE et al. ICAAC (2009). D803.
Disc testing
MIC testing• “Gold Standard”:
– Microbroth dilution MIC– ISO 20776– MH broth
• Ease of use standard:– Gradient strips– (Etest, MICE, MICtest)
0.5
0.750
0000
0000
0001 1 1.5 2
02468
1012
Vancomycin vs. ATCC 29213
V Etest MHAV MICE MHAV Etest ISOV MICE ISO
Replicate testing (x15) of QC strains by MICE & Etest gradient strips
CLSI QC Range: 0.5 – 2 mg/L
Richards J et al. ECCMID (2012). P1652.
• 8 VISA, 59 VSSA(MRSA)
• MIC determination by– Etest (BioMerieux)– MICE (Oxoid)– MIC test
(Liofilchem/Launch diagnostics)
– ISO MBD.
Richards J et al. ECCMID (2012). P1652.
• 182 pts with SAB
• Related vancomycin AUC/MIC to outcome(target >400)
• Median AUC/MIC– MBD – 436.1– Etest - 271.5
• CART analysis– AUC/MIC (MBD)
>373 assoc with ↓mortality
0.25 0.38 0.5 0.75 1 1.5 2 30
20406080
100120140160
Etest BMD
MIC (mg/L)
No
of is
olat
es
Holmes et al AAC (2013) epub.doi:10.1128/AAC.01485-12
“Etest tends to give slightly higher MICs”
Commercial systems• Vitek2 undercalls
resistance• Phoenix overcalls
resistance
Swenson et al. (2009) JCM 47: 2013
Method SN SP NPV PPV hGISA GISA Total GI hGISA GISA Total GI MET 58.8 92.3 71.1 100 70.4 96.2 69.4 100 GRD (24) 58.8 100 72.7 100 70.4 100 70.4 100 GRD (48) 80.4 100 87 100 83.3 100 83.3 100
Screening tests
BHIA6V MHA5T MET0
25
50
75
100
SDBHIA6V - 14.59MHA5T - 9.93
MET - 8.44
Method type
%ag
e st
rain
s co
rrec
tly
CT
'd p
er la
b
% Sensitivity
% Specificity
BHI - 4V 71 88 Macro Etest 96 97 BHI - 6V 22 97 MHA - 5V 20 99
• Screening agars– BHI/MHA– V/T – 4/5/6– MHA5T best
– Macro Etest (2 McF)– Good performance
– GRD Etest (0.5 McF)– Good performance
Walsh et al (2001) JCM 39: 2439Wootton et al (2007) JCM 45: 329Wootton et al (2008) ICAAC D2214
Conclusions• Aim to identify MIC >2mg/L• Closeness of BP to MICs of wild population
challenges all methods• Disc testing not reliable• MIC methods require close attention to QC/QA• Automated systems struggle• Population analysis can confirm reduced
susceptibility• Screening methods may have a role but lack
sensitivity
Current recommendations• Do not use disc testing• Use MIC method
– BMD gold standard– Control all tests with QC strains
(monitor QC results for trends even within appropriate QC range)
• Consider targeted testing
AcknowledgementsDr Mandy WoottonLeanne DaviesJennifer RichardsProf Tim Walsh
Jenny AndrewsBSAC AST Working Group