EUCAST-AFST Available breakpoints 2012

Transcription

1 EUCAST-AFST Available breakpoints th NSMM meeting Göteborg, Sweden October th

2 EUCAST-AFST documents Reference Methods Yeast E.DEF. () TN- E.DEF. (CMI epub July) E.DEF. () TN- E.DEF. () Breakpoints Compound Candida Conidia forming moulds E.DEF. () TN-E.DEF. () Aspergillus Rationale Doc Techn. Note CMI Rationale Doc Techn. Note CMI Amphotericin epub July Anidulafungin Fluconazole - - Itraconazole epub July Posaconazole epub July Voriconazole In prep.

3 EUCAST BP establishing procedure MIC distributions Per species Several data sets Epidemiological Cut Off Value (ECOFF) MIC-clinical outcome relationships Per species For wild type and non-wild type isolates PK/PD defining the important parameter and ratio (AUC/MIC, Peak/MIC, Time/MIC) are non wild type covered during standard dosing? BP never higher than ECOFF unless supported by data

4 EUCAST Candida BPs Breakpoints (BPs): S: X / R: >Y Antifungal agent C. albicans C. glabrata C. krusei MIC breakpoint (mg/l) C. parapsilosis C. tropicalis C. guilliermondii Non-species related breakpoints Ampho. B / / / / / IE IE Anidulafungin./../../. -*./. IE IE Fluconazole / IE* - / / IE / Posaconazole./. IE IE./../. IE IE Voriconazole./. IE IE./../. IE IE denotes the MICs for this species is generally higher than those for C. albicans denotes that voriconazole should be reserved for situations where fluconazole is not appropriate - denotes the organism is regarded a poor target for the antimicrobial agent Current revision proposals *For C. glabrata and fluconazole it is proposed to categorise mg/l as I and > mg/l as R *For C. parapsilosis and anidulafungin it is proposed to categorise mg/l as I and > mg/l as R Breakpoints under development: Micafungin and Candida

5 CLSI versus EUCAST Breakpoints (BPs): S: X; R: >Y CLSI M-S CLSI revised (M-S) EUCAST AMB ; > ANF.; >. (alb, krus, trop).; >. (glab) ; > (para, guillier) CSF - MFG.; >. (alb, krus, trop).; >. (glab) ; > (para, guillier) Fluco ; > ; > (alb, para, trop) SDD ; > (glab) (krus poor target) Vori ; >.; >. (alb, para, trop).; > Revised BPs (krus).; >. (alb).; >. (glab, krus, trop) (para poor target, guillier IE) Pfaller Drug Resist Updat. EUCAST-AFST: & MC Arendrup (Chair), WW Hope (Secretary), M Cuenca-Estrella & C Lass-Flörl - ; > (alb, trop, para) (glab IE) (krus poor target).; >. (alb, trop, para) (glab/krus IE) (glab IE) Itra.; >..; >. - Posa - -.; >. (alb, trop, para) (glab/krus IE)

6 A N I. CLSI echinocandin MICs M-S BP C. albicans C. glabrata C. krusei C. parapsilosis C. tropicalis.. C. albicans (S) C. albicans (R)... C. glabrata (S) C. glabrata (R)... C. krusei (S) C. krusei (R)... C. parapsilosis (S)... C. tropicalis (S) C. tropicalis (R) C A S C. albicans (S) C. albicans (R) C. glabrata (S) C. glabrata (R) C. krusei (S) C. krusei (R) C. parapsilosis (S) C. tropicalis (S) C. tropicalis (R) M I C A... C. albicans (S) C. albicans (R) Arendrup et al AAC, CLSI M-S... C. glabrata (S) C. glabrata (R)... C. krusei (S) C. krusei (R)... C. parapsilosis (S)... C. tropicalis (S) C. tropicalis (R)

7 CLSI echinocandin testing revised BP A N I C. albicans C. glabrata C. krusei C. parapsilosis C. tropicalis C. albicans (S) C. albicans (R) C. glabrata (S) C. glabrata (R) C. krusei (S) C. krusei (R) C. parapsilosis (S) C. tropicalis (S) C. tropicalis (R) C A S C. albicans (S) C. albicans (R) C. glabrata (S) C. glabrata (R) C. krusei (S) C. krusei (R) C. parapsilosis (S) C. tropicalis (S) C. tropicalis (R) M I C A... C. albicans (S) C. albicans (R) Arendrup AAC, Pfaller Drug Res Updates, M-S... C. glabrata (S) C. glabrata (R)... C. krusei (S) C. krusei (R)... C. parapsilosis (S)... C. tropicalis (S) C. tropicalis (R)

8 EUCAST & CLSI Anidulafungin MICs Candida sp >= ECOFF BP albicans EUCAST * *.. albicans CLSI.. glabrata EUCAST * *.. glabrata CLSI.. krusei EUCAST * *.. krusei CLSI.. parapsilosis EUCAST - parapsilosis CLSI tropicalis EUCAST * *.. tropicalis CLSI.. and

9 Etest: Caspofungin and CLSI BP % % C. albicans() Etest % % C. glabrata () Etest % -% -% -% CLSI () % % -% -% -% CLSI () MIC (mg/l) Titel % % % % % % -% -% -% -% -% C. tropicalis () Etest CLSI () % % % % -% -% -% C. krusei () Etest CLSI () Arendrup & Pfaller AAC Titel Titel

10 EUCAST Aspergillus BPs BPs indicated as S x / R >y AF compound Aspergillus flavus fumigatus nidulans niger terreus Amphotericin IE* / Note / Poor Target Itraconazole / / / IE* / Posaconazole IE*./.** IE* IE* Note Voriconazole Note / Note Note Note * MICs are higher than for A. fumigatus ** provided sufficient levels can be achieved Note: the MICs are similar to A. fumigatus but insufficient clinical data for BP setting

11 Website update: the AFST tab

12 May thanks for your attention Steering Committee MC Arendrup, Chair (Denmark) W Hope, Secretary (UK) C Lass-Flörl(Austria) M Cuenca-Estrella (Spain) General committee S Arikan-Akdagli(Turkey) F Barchiesi(Italy) J Bille(Switzerland) E Chryssanthou(Sweden) P Gaustad(Norway) A Groll(Germany) P Haml(Czech Republic) H Järv(Estonia) K Lagrou(Belgium) O Lortholary(France) N Klimko(Russia) T Matos (Slovenia) C Moore (UK) A Velegraki(Greece) P Verweij(The Netherlands)