Comparing Minimum Inhibitory Concentration and Minimum Bactericidal Concentration Results for Brachyspira Species – What is the Difference?
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) | ||||
---|---|---|---|---|
Antibiotic | No. of isolates | MIC 50 | MIC 90 | MIC 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 |
Antibiotic | No. of isolates | MBC 50 | MBC 90 | MBC 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 | ||
---|---|---|
Antibiotic | In 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
- Burch, D.G.S. 2005. Pig Journal, 56:8-24.
- Anderson, M.D. et al., 1996. Proc. AASP Meeting, 115-118.
- 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