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 g/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 g/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 g/ml. The testing range for Ampicillin is 0.25 - 32 g/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 g/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.

If the result is: Then the antibiotic is: Further info/action:
S <= (any number) Effective at lowest dilution tested. Should be effective in serum or urine.
S (any number) Effective, but not at lowest dilution tested. Refer to MIC ranges to determine where in range it tested and decide if it is a good choice.
I (any number) May be effective in high dosages, or if it concentrates in the site. Refer to references for achievable Antibiotic levels in affected tissue.
R (any number) Will be unlikely to reach effective serum levels. Choose an antibiotic that tests susceptible. (See below).
R >= (any number) Unlikely to be effective. Choose an antibiotic that tests susceptible. However, if all antibiotics are resistant, an antibiotic may need to be chosen that can reach higher levels in the affected tissue than in the plasma.

When determining which antibiotic is best, consider safety, ease-of-use, and cost along with the MIC and the S-I-R interpretation.

The charts on the next page should help in your decision process. Listed below are several good references if you would like additional information; or call our clinical pathology/internal medicine consultants at 1-800-444-4210 (option 1).

Target, Antimicrobial Reference Guide to Effective Treatment, David Aucoin, DVM, North American Compendiums Inc., 2nd edition, 2000.

Infectious Disease of the Dog and Cat, Greene, W.B. Saunders, 2nd edition, 1998.

Package inserts from Antibiotics.

 

 

 

MIC Ranges Tested and Interpretation

ANTIBIOTIC
ORGANISM TYPE TESTED
Test Range ug/mL
Interpretations Based on Plasma Levels of Antibiotic
Interpretation Based on Urine Levels of Antibiotic
 
 
 
S
I
R
S
R
Amikacin Gram neg
2-64
2-16
32
64
2-32
64
Amox/Clav Gram neg
8-32
8
16
32
8-16
32
  Staph
2-8
2-4
 
8
2-4
8
Ampicillin Gram neg
0.25-32
0.25-8
16
32
0.25-16
32
  Staph
0.12-16
0.12-0.25
 
0.5-16
0.12-8
16
  Enterococcus
0.12-16
0.12-8
 
16
0.12-8
16
Carbenicillin Gram neg, enteric
16-512
16
32
64-512
 
 
  Gram neg, Pseudo
16-512
16-128
256
512
 
 
Ceftazidime Gram neg
8-32
8
16
32
 
 
Ceftiofur All
1-8
1
2-4
8
 
 
Cephalothin All
2-32
2-8
16
32
2-16
32
Chloramphenicol All
1-32
1-8
16
32
1-16
32
Ciprofloxacin Gram neg
0.5-4
0.5-1
2
4
 
 
Clindamycin Staph
0.5-8
0.5
1-2
4-8
 
 
Enrofloxacin All
0.25-2
0.25
0.5-1
2
0.25-1
2
Erythromycin Staph
0.5-8
0.5
1-4
8
 
 
Gentamicin All
0.5-16
0.5-4
8
16
0.5-8
16
Nitrofurantoin Gram neg
32-128
NA
NA
NA
32-64
128
Oxacillin Staph
0.25-8
0.25-2
 
4-8
 
 
Penicillin G Staph
0.03-16
0.03-0.12
 
0.25-16
 
 
  Enterococcus
0.03-16
.0.03-8
 
16
 
 
Piperacillin Gram neg, enteric
8-256
8-16
32-64
128-256
 
 
  Gram neg, Pseudo
8-256
8-64
 
128-256
 
 
Tetracycline All
1-16
1-4
8
16
1-8
16
Ticarcillin Gram neg, enteric
16-256
16
32-64
128-256
 
 
  Gram neg, Pseudo
16-256
16-64
 
128-256
 
 
Tobramycin Gram neg
0.5-16
0.5-4
8
16
 
 
Trimeth/sulfa All
10-320
10-40
 
80-320
10-80
160-320
Vancomycin Staph
0.5-32
0.5-4
8-16
32
 
 
  Enterococcus
0.5-32
0.5-4
8-16
32
 
 
Notes:
1. Urine values are given only if different from serum values.
2. Trimeth/sulfa expressed in combined amount of trimethoprim + sulfa fractions


Mean Urine Concentrations of Selected Antibiotics

 
Antibiotic Dosage (mg/kg) Route Interval Mean Urine Concentration (g/mL)
Ampicillin 22 PO 8 309
Amoxicillin 11 PO 8 201.5
Chloramphenicol 33 PO 8 124
Nitrofurantoin 4.4 PO 8 100
Trimeth/sulfa 13 PO 12 26/79 = 105 (combined)
Gentamicin 2 SC 8 107
Amikacin 5 SC 8 342
Cephalexin 8 PO 8 225
Enrofloxacin 2.5 PO 12 40
Tetracycline 18 PO 8 138
Reference: Infectious Diseases of the Dog and Cat, Greene, 2nd ed, W.B.Saunders, 1998.

Keep this sheet for reference.