1. CLSI/VAST approach for breakpoints definition.
- Author
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Papich, Mark G.
- Subjects
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PATHOGENIC microorganisms , *VETERINARY medicine , *VETERINARY drug testing , *VETERINARY drugs , *ANTI-infective agents - Abstract
On June 28, 2018 the Clinical Laboratory Standards Institute (CLSI) Veterinary Antimicrobial Susceptibility Testing (VAST) subcommittee published the new standards for susceptibility testing (www.CLSI.org). These documents are the newest standards, representing over 20 years of developing susceptibility testing standards for pathogens isolated from animals. CLSI-VAST is the only organization in the world that has published breakpoints for animal pathogens. The current edition of the CLSI standard document has approximately 180 breakpoints for drug-bacteria combinations in the major veterinary species. There are now breakpoints for practically every approved antimicrobial agent for the label indication in veterinary medicine. CLSI-VAST is working to fill the gaps for the few agents that do not have clinical veterinary breakpoints. Because there are many human-labeled antimicrobial agents used in veterinary medicine, CLSI also has developed clinical breakpoints for these agents in the non-food animal species. CLSI-VAST develops the breakpoints through a rigorous process, using strict criteria. Sponsors are required to follow guidelines provided by CLSI and must submit data to support a proposed breakpoint. The data includes pharmacokinetic data in the target species, MIC distributions for the pathogens targeted, clinical data from the drug used under field conditions at the approved dose, and pharmacokinetic-pharmacodynamic (PK-PD) analysis, using Monte Carlo Simulations, to show that at the approved dose, the drug attains PK-PD targets for the labeled pathogen. For older agents that no longer have sponsors (generic drugs), a separate Working Group has developed guidelines to establish breakpoints for these agents. The Working Group uses PK-PD analysis, Monte Carlo simulations, MIC distribution data from laboratories, and published evidence of clinical experience. The CLSI uses a consensus-driven process. The consensus process involves the development and open review of documents, revision of documents in response to discussion, and, finally, the acceptance of a document as a consensus standard. All CLSI meetings are open to the public and all opinions are considered. When accepted, the CLSI breakpoints are regarded as a public standard, not a guideline. The standard documents developed through the consensus process identifies specific, essential requirements for materials, methods, or practices for use in an unmodified form. In order to follow the CLSI standard, the testing methods must be followed, including standardized media and test conditions. MIC data generated in media other than CLSI standard media (eg, Mueller-Hinton Broth), or alternative test conditions are not acceptable. [ABSTRACT FROM AUTHOR]
- Published
- 2018