The EUCAST/VETCAST approach to breakpoint definition and determination.

Abstract

VetCAST is the EUCAST (European Committee on Antimicrobial Susceptibility Testing) subcommittee for veterinary Antimicrobial Susceptibility Testing (AST). Its remit is both to define and harmonise clinical breakpoints (CBPs) for antimicrobial drugs (AMDs) used in veterinary medicine in Europe. This presentation outlines the procedures and reviews scientific options for solving challenges to the determination of specific CBPs for animal species, drug substances and disease conditions. VetCAST has adopted EUCAST approaches: the initial scientific step comprises data assessment; followed by procedures for decisions on the CBPs that include non-scientific considerations,and finally the release of recommendations for CBP implementation. The principal challenges facing VetCAST are those associated with the differing modalities of AMD administration, including mass medication, longacting product formulations and local administration. Specific challenges comprise: breakpoint determination for mastitis treatment in dairy cattle,the range of species and within species breed considerations,and several additional variable factors not relevant in human medicine. These factors may prevent adoption of a single CBP covering all situations. Each CBP will be based on: (i) an epidemiological cut-off value (ECOFF) - the highest MIC that defines the upper end of the wild-type MIC distribution,(ii) a PK/PD breakpoint based on pre-clinical pharmacokinetic data [it is the highest possible MIC for which a given percentage of animals (e.g. 90%) in the target population achieves a critical value for the selected PK/PD index (fAUC/MIC or fT>MIC)],and (iii) when possible, a clinical cut-off, which takes account of the relationship between MIC and clinical cure. For the latter, VetCAST acknowledges the paucity of such publicly available data in veterinary medicine. In consequence, the PK/PD breakpoint plays a pivotal role for VetCAST, as is similarly the case for EUCAST. When a CBP cannot be established, VetCAST will recommend use of ECOFF as a surrogate. For decision steps, VetCAST will follow EUCAST procedures involving transparency, consensus and independence. VetCAST will ensure free availability and widespread dissemination of information, concerning standards, guidelines, ECOFF, PK/PD breakpoints, CBPs and other relevant information for AST implementation. Finally, after establishing a CBP, VetCAST will promulgate widely expert comments and/or recommendations on CBPs to facilitate scientifically sound implementation in a clinical setting. VetCAST currently has 52 members and is currently completing its first clinical breakpoint definition (florfenicol in cattle against Pasteurella multocida and Mannheimia haemolytica). [ABSTRACT FROM AUTHOR]