Microbiology Guide to Interpreting MIC (Minimum Inhibitory Concentration)

Linda Matros, DVM, DACVIM • Terri Wheeler, DVM • and the Microbiology Team • IVS Sacramento
February 2001

Until recently most in vitro susceptibility testing was performed by disk diffusion (Kirby-Bauer). The size of the growth-free zone determined whether the bacterium was considered to be susceptible, resistant, or intermediate to a particular antibiotic.

While used as a guide to select an effective antibiotic, Kirby-Bauer testing could not tell the clinician the exact concentration of antibiotic needed to achieve a therapeutic result. Now by a quantitative method of susceptibility testing known as the MIC, the precise concentration of antibiotic required to inhibit growth of a pathogen can be determined.

This Diagnostic Update provides a detailed explanation of the following concepts important in implementing the MIC: The MIC number is the lowest concentration (in µg/mL) that inhibits the growth of a given strain of bacteria. (see "What is the MIC?") A MIC number for one antibiotic can NOT be compared to the MIC number for another antibiotic. (see "How to Use the MIC Number") The choice of antibiotic should be based on: the MIC number, the site of infection and an antibiotic's breakpoint. Consider safety, ease of use and cost when determining the optimum antibiotic. The attached tables will aid in MIC interpretation and antibiotic selection.

What is the MIC?

The Minimum Inhibitory Concentration (MIC) is determined by inoculating the organism into a series of test wells, usually 4 to 6, that contain a standard amount of broth and serial dilutions of the antibiotic being tested. Following a period of incubation, the wells are examined for growth.

The MIC number is the lowest concentration of drug that inhibits growth of the pathogen. Usually, successful treatment of infection can be achieved by merely inhibiting multiplication of the microorganism and relying on a healthy immune system.

The amount of antibiotic required to inhibit growth is not the same as the amount required to actually kill the organism. The Minimal Bactericidal Concentration (MBC) is usually several dilutions greater than the MIC. This fact becomes important to remember when treating patients with compromised immune systems.

In infections where the host's natural defense mechanisms are impaired, successful treatment depends upon achieving bactericidal concentrations of antibiotic.

How is the MIC reported?

When you receive a report from IDEXX Veterinary Services, you will see the name of the organism, followed by a list of the antibiotics that have been tested against that organism. We test a panel of antibiotics known to be appropriate for the organism. Our antibiotic panels have been designed based on recommendations set by the National Committee on Clinical Laboratory Standards (NCCLS). This organization recommends standards for all laboratory testing (human and veterinary).

Following each antibiotic listed you will find one of three letters: S(Susceptible), I(Intermediate), or R (Resistant). This is followed by a number (the Minimum Inhibitory Concentration in µg/mL) which is the lowest drug concentration that inhibited the growth of the organism.

When "<=" is listed in the report, the organism was inhibited at the lowest dilution tested for that drug.

Example: Ampicillin S <= 0.25. Interpretation:
This organism is susceptible to Ampicillin at the lowest dilution tested.

How to Use the MIC number
The MIC number for one antibiotic can NOT be compared to the MIC number for another antibiotic because a MIC cannot be interpreted based on absolute values alone. You also have to know the range tested and the breakpoint for each antibiotic.

The MIC is the lowest concentration of drug in ug/mL that inhibits the growth of a strain of bacteria. The Breakpoint is the highest plasma concentration of the drug that can safely be achieved in the patient. This corresponds to the lowest concentration listed in the "R" section of the table on the next page "MIC Ranges Tested".

The Breakpoint differs by drug and species of animal and is based on pharmacokinetic testing of the drug in that species to determine half-life, routes of excretion, and volume of distribution.

For example, if we look at Ampicillin, the breakpoint for resistance against gram negative bacteria is 32 µg/ml. The testing range for Ampicillin is 0.25 - 32 µg/mL. An E. coli with a MIC <= 8 is interpreted as susceptible, an MIC of 16 is intermediate, and >= 32 is resistant. An E. coli with a MIC of 1 ug/mL is considered more susceptible than an E. coli of 8 µg/ml, and an E. coli of >=32 ug/ml is considered resistant to Ampicillin.

Some antibiotics have different MIC ranges and Breakpoints for different types of bacteria. In general the higher the MIC within the range tested, the less likelihood that the organism will be susceptible.

MIC interpretations, except for urines, are based on plasma levels but some antibiotics reach much higher tissue levels than plasma levels. This fact is important if an organism shows resistance to most or all antibiotics tested. If the MICs are in the >= R range, these antibiotics cannot reach a known inhibitory concentration. In those cases, it may be that an antibiotic must be selected by determining which choice can reach higher concentrations in the affected tissue.

Increasing the dose and/or the frequency of administration may help inhibit resistant organisms. Remember that in most cases, the patient's natural defense mechanisms work with the antibiotic to result in a successful response.

The following MIC KEY is to help interpret the MIC value on the microbiology report.