Susceptibility Testing and Clinical Response

The need to control and limit the emergence of microbial resistance has led to the development of different strategies to decrease an inappropriate antimicrobial use in veterinary medicine. The definition of microbial susceptibility and the connection of therapy with a clinical response are important issues. These have to consider many aspects: 1. the evaluation of the susceptibility of the pathogen defining the MIC distribution; 2. the definition of the pharmacokinetics in the target species; 3. the collection of clinical data from drugs use in field condition; 4. the optimization of drugs dosage by PK/PD correlation and the use of in silico simulations to show that the dose approved reaches PK/PD target for the specific pathogen. The antimicrobial susceptibility testing (AST), used to define MIC distribution, has to follow standardised procedures and guidelines accepted by International agencies, as the Clinical and Laboratory Standards Institute (CLSI) and FDA in the US and the EU Committee on Antimicrobial Susceptibility Testing (EUCAST) and EMA in Europe, with veterinary subcommittees, CLSI - VAST and EUCAST - VetCAST. The adherence with accepted guidelines is very important to provide reproducible, updated and significant data. The responsibility of these agencies is also the setting of clinical breakpoints to indicate the probability of success of an antimicrobial therapy by defining the pathogens as susceptible “S”, intermediate “I” or resistant “R”. These are disease-indication and target-animal-species specific. The definition of clinical breakpoints considers epidemiological cut-off values (ECOFF) or wild-type cutoff (COwt), PK/PD cutoff (COPK/PD) and clinical cutoff (COcl). The VAST committee has defined clinical breakpoints for new and generic veterinary antimicrobial agents. Whereas, the recently formed VetCAST committee has just started its work to propose veterinary specific breakpoints. The collection of clinical data after treatment and the definition of clinical cure is still a limited issue in veterinary daily practice. Moreover, the correlation of clinical outcome with in vitro diagnosis is a complex matter that carries some limitations. Nevertheless, the use of veterinary approved breakpoints to choose the most appropriate antimicrobial treatment helps the practitioner in the therapy and is a milestone for the prudent use of the drug.