Antimicrobial susceptibility testing part 4 – Laboratory results interpretation

Ðurđa Slavić

Animal Health Laboratory, University of Guelph, Guelph, ON.

AHL Newsletter 2022;26(3):8.

AHL previously published information about antimicrobial susceptibility test methods, selection of bacterial organisms, and selection of antimicrobials for antimicrobial susceptibility testing (AST).  In this fourth article of the series, laboratory results interpretation is discussed.  The full document is available on the AHL website as Labnote 64: https://www.uoguelph.ca/ahl/ahl-labnote-64-antimicrobial-susceptibility-testing-ast

When it comes to interpretation of AST results, the Clinical and Laboratory Standards Institute (CLSI) provides a breakpoint for different drugs which is translated into an interpretative category (i.e., S, I, and R).  As per CLSI: “breakpoint is minimal inhibitory concentration or zone diameter value used to categorize an organism as susceptible, intermediate or resistant.”  When available, the Veterinary Antimicrobial Susceptibility Testing (VAST) subcommittee recommends use of veterinary-specific clinical breakpoints because they are determined based on microbiological characteristics, pharmacokinetic and pharmacodynamics parameters, and/or clinical outcome (Table 1).  However, veterinary-specific clinical breakpoints are not available for every drug/bacterial species/disease combination.  At present, there are veterinary-specific guidelines available for some veterinary pathogens associated with urinary tract infection primarily in dogs and cats, respiratory infections primarily in cattle and swine, mastitis in cattle, metritis, abscesses, and wound, skin and soft tissue infections.  In some cases, human clinical breakpoints are still used, or results are extrapolated from similar veterinary drug/bacterial species/disease combination (i.e., M. haemolytica respiratory breakpoints are used to predict susceptibility of Bibersteinia trehalosi in bovine respiratory samples).

This is what it means to get S, I, or R results, as per CLSI:

“Susceptible (S) – a category defined by a breakpoint that implies that isolates with an MIC at or below or a zone diameter at or above the susceptible breakpoint are inhibited by the usually achievable concentrations of antimicrobial agent when the dosage recommended to treat the site of infection is used, resulting in likely clinical efficiency.” 

“Intermediate (I) – a category defined by a breakpoint that includes isolates with an MIC or zone diameter within the intermediate range that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates.  The intermediate category implies clinical efficacy in body sites where the drugs are physiologically concentrated or when a higher than normal dosage of drug can be used.  This category also serves as a buffer zone to prevent the inherent variability of antimicrobial susceptibility testing methods from leading to erroneous categorization.” 

“Resistant (R) – a category defined by a breakpoint that implies that isolates with an MIC at or above or a zone diameter at or below the resistant breakpoint are not inhibited by the usually achievable concentrations of the agent within normal dosage schedules and/or that specific microbial resistance mechanism are likely, and clinical efficacy of the agent against the isolate has not been reliably shown in isolates with similar phenotypes.”   AHL

Table 1.  List of antimicrobial agents that have CLSI-approved veterinary specific breakpoints.

Reprinted with permission from Clinical and Laboratory Standards Institute: CLSI. Understanding susceptibility test data as a component of antimicrobial stewardship in veterinary settings. 1st ed. CLSI report VET09. Wayne, PA: Clinical and Laboratory Standards Institute; 2019.