Breakpoints

The Clinical Laboratories Standard Institute (CLSI) and the European Committee on Antibiotic Susceptibility Testing (EUCAST) define breakpoints for bacteria spp/drug combinations. The breakpoint is the concentration of antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic. For a given antibiotic, the breakpoint may differ for different sites (e.g., urine versus tissues or skin) and for different organisms.

Minimum Inhibitory Concentration or MIC is defined as the lowest concentration of an antibiotic which prevents visible growth of a bacterium. MICs are determined by using a serial dilution method. Bacteria are added to wells containing serially diluted concentrations of antibiotics.  Growth or no-growth at each concentration of antibiotic is measured in the analyser from the turbidity of the well at a given timepoint. The MIC is then compared to the breakpoint – if the MIC is less than the breakpoint, the organism is susceptible, whilst if the MIC is higher than the breakpoint, it is resistant.

The further the MIC value is away from the breakpoint, the lower the concentration of antibiotic required to successfully treat the bacterial infection and so the more susceptible the organism is to that antibiotic. The antibiotic to which the organisms is most susceptible is the one that is the highest number of serial dilutions below the breakpoint value as shown in the example:

Antibiotic MIC Interpretation Sensitive Intermediate Resistant
Ampicillin 32 R <=8 >=16
Amoxicillin/Clav 32 S <=8 >=16
Marbofloxacin 0.5 S <=1 2 >=14
Gentamicin 1 S <=2 4 >=8
Trimethoprim-Sulf 20 S <=40 >=80

 

Sensitive Antibiotics Number of Dilutions Away from the Breakpoint
Amoxyclav 2 (8÷2=4÷2=2)
Marbofloxacin 1 (1÷2=0.5)
Gentamicin 1 (2÷2=1)
Trimethoprim-Sulf 1 (40÷2=20)

In this example amoxyclav is the most sensitive.

The lowest MIC value is for marbofloxacin, BUT this is not the most sensitive antibiotic.

The site of infection should also be considered when selecting the antibiotic – e.g., for prostatitis TMPS or marbofloxacin would be preferable as they penetrate into prostatic tissue better than amoxiclav.

Results Without MIC Values

Occasionally, some of the results received will either not have MIC values, or contain results where some antibiotics have MIC values, and some do not. This occurs when:

    • There are no validated MIC values for the organism in question, but there are validated Kirby-Bauer Disk Diffusion zone sizes and so the disc diffusion method is used to determine susceptibility.
    • The result has been inferred from the MIC value for another antibiotic as approved by international governing bodies. E.G. for Streptococcus canis: amoxicillin, ampicillin, cephalexin can be inferred from the benzylpenicillin susceptibility result (CLSI).
  • The Vitek analyser does not offer MIC testing for all antibiotics. E.G. there are limited topical antibiotics available for testing, and so the majority of topical antibiotics are tested using the Kirby Bauer Disk Diffusion method.
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