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Comparing Minimum Inhibitory Concentration and Minimum Bactericidal Concentration Results for Brachyspira Species – What is the Difference?

1 October 2013, at 12:00am

Antibiotics tested, which are classified as bacteriostatic against Brachyspira, have bactericidal properties at approximately double the minimum inhibitory concentration, according to new research from the UK by David Burch and others.

The terminology used to describe the antimicrobial resistance breakpoint value for Brachyspira species can be confusing and ill-defined. The most commonly used term, minimum inhibitory concentration (MIC), can variably be used to indicate the lowest concentration at which clear inhibition of bacterial growth has occurred, or in some laboratories, the lowest concentration at which no bacterial growth occurs. The latter circumstance describes the minimum bactericidal concentration (MBC) and this result can differ from the MIC by up to 2 doubling dilutions.

Attributing the correct term and cut-off in the test is particularly important for assessing the efficacy of agents that work by inhibiting the target organism.

Comparative MIC and MBC results for Brachyspira hyodysenteriae are presented and compared with antimicrobial concentrations achieved in the colon contents, to estimate clinical break-points.

Material and Methods

MIC/MBC determination

The MIC and MBC were determined using the agar dilution method with the specified antibiotic incorporated in serial two-fold dilutions from 0.031μg per ml to 128μg per ml. Determination of the MIC and MBC values was done in accordance with the standard operating procedure for the test.

Isolates

The isolates of B. hyodysenteriae were cultured from clinical samples submitted to SAC Veterinary Services, Edinburgh between the years 2004 and 2013. Samples were from pigs with a history of diarrhoea, mostly from herds in the UK.

Pharmacokinetics

The concentration of an antibiotic achieved in the colon contents has been suggested as the most suitable pharmacokinetic parameter to determine the likely efficacy of a drug against B. hyodysenteriae (1). There is some published data available giving this information but this is usually based on extraction of the drug from the contents and does not take into account binding to caecal contents, which is generally unreported.

Results

The results of the MIC and MBC determinations are summarised in Table 1. Colon contents concentrations (CCCs) are in Table 2.

Table 1. Summary of MIC and MBC results (µg/ml)
AntibioticNo. of isolatesMIC 50MIC 90MIC range
Tiamulin 86 0.125 4.0 <0.031-32
Lincomycin 66 16 64 <0.031->128
Tylvalosin 45 8.0 32 0.5-64
Valnemulin 47 0.031 1.0 <0.031-16
AntibioticNo. of isolatesMBC 50MBC 90MBC range
Tiamulin 86 0.25 4.0 <0.031-32
Lincomycin 66 32 128 <0.031->128
Tylvalosin 45 16 32 0.5->128
Valnemulin 47 <0.031 2.0 <0.031-16

Table 2. Colon contents concentrations various antibiotics
AntibioticIn feed (ppm)CCC (µg/g)
Tiamulin 220(2) 8.05
110 2.84
40E 1.03
Tylvalosin 82.5E(1) 16
Lincomycin 220(3) 101
110 34.5
44E 13.8
Valnemulin 200(1) 5.6
75 1.6
25E 0.53
Key: E = Estimated; CCC = Colon contents concentrations.

Discussion

Most MIC/MBC 50 ratios are 1:2 for all the antibiotics tested suggesting that these antibiotics, which are classified as bacteriostatic, do have bactericidal properties at approximately double the MIC. At the MIC 90s, potentially resistant bacteria are present, so results are more variable.

Establishing clinical break-points are also difficult as different concentrations of the antibiotic can be used for different purposes, or indications. However, this information, if established, would be of great value to pig veterinarians.

References

  1. Burch, D.G.S. 2005. Pig Journal, 56:8-24.
  2. Anderson, M.D. et al., 1996. Proc. AASP Meeting, 115-118.
  3. Degeeter, M.J. et al., 1980. Proc. IPVS Congress, 283.

By David Burch1, Jill Thomson2, Brian Murray2 and Joe Docherty2. Octagon Services Ltd, Old Windsor, Berkshire, UK1, SAC Veterinary services, Bush Estate, Penicuik, Midlothian, UK2 .

Presented as a poster at 6th International Conference on Colonic Spirochaetes in Animals and Humans 2013, University of Surrey, UK. 5-6 September 2013.

October 2013