On the Oral Antimicrobial Pharmacokinetics spreadsheet we tabulated the major pharmacokinetic characteristics of most of the major oral antimicrobials medicines used in pigs. The concentrations that can be found in blood, for systemic infections, lung, for respiratory infections and colon, for enteric infections are described as far as possible. These can then be compared with the minimal inhibitory concentrations (MICs) of the various antimicrobials against the various pig pathogens, which cause disease and are tabulated below. These are divided up into two main groups, enteric pathogens and respiratory pathogens.
| Enteric infections | Respiratory infections |
| 1. Escherichia coli | 1. Mycoplasma hyopneumoniae |
| 2. Salmonella spp | 2. Pasteurella multocida/Bordetella bronchiseptica |
| 3. Brachyspira hyodysenteriae | 3. Actinobacillus pleuropneumoniae |
| 4. Brachyspira pilosicoli | 4. Haemophilus parasuis |
| 5. Lawsonia intracellularis | 5. Streptococcus suis |
| 6. Clostridium perfringens |
In some cases there is no comparative MIC data only sensitivity data based on disc diffusion tests and sometimes from a number of countries. The MIC is the lowest concentration of an antimicrobial, which will inhibit the growth of an organism. Often there is an MIC 50 figure, which means that concentration will inhibit 50% of the different strains of bacteria in the study. Similarly the MIC 90 is the concentration that inhibits 90% of the strains and the range is the variation between sensitive and non-sensitive strains. The effective concentration or breakpoint can be determined where the concentration in the blood or target tissue is, this should be ideally higher than the MIC90 for the particular bacterium so there is a good chance of successful treatment. At that concentration it will usually inhibit its growth and allow the body's own immune system to destroy the bacterium (bacteriostatic effect). Some antibacterials and some bacteriostatic ones at high concentrations will kill a bacterium directly and this is known as bactericidal effect. The tetracyclines, macrolides and pleuromutilins have primarily a bacteriostatic effect and the quinolones, penicillins and aminoglycosides are bactericidal.
Enteric infections:
- Escherichia coli.
Antimicrobial |
Sensitivity (%) |
|
|
|
|
|
|
Ampicillin/Amoxycillin Apramycin Cephalotin Enrofloxacin Gentamicin Neomycin Spectinomycin Sulfisoxazole Tetracycline Trimethoprim/sulpha |
53 90 47 99 75 53 31 23 14 72 |
55 85 - 97 - 82 - - 17 52 |
Source: (1. Laperle et al., 1996; 2. DEFRA, 2001)
2. Salmonella spp.
|
|
Sensitivity
(%) |
|
|
|
|
|
|
Ampicillin Apramycin Cephalotin Enrofloxacin Gentamicin Neomycin Spectinomycin Sulfisoxazole Tetracycline Trimethoprim/sulpha |
94 100 100 94 78 89 56 18 50 72 |
54 96 - 94 (nalidixic acid) - 97 - 25 17 58 |
Source: (1. Laperle et al., 1996; 2. Veterinary Laboratories Agency Report, 1999)
3.
Brachyspira hyodysenteriae (
Antimicrobial |
MIC50 |
MIC90 |
Range (μg/ml) |
MIC
breakpoint* |
|
Valnemulin Tiamulin Lincomycin Tylosin Dimetridazole |
0.1 0.3 50.0 200.0 30.0 |
4.0 1.0 100.0 >200.0 >40.0 |
0.025-4.0 0.025-1.0 1.0-100.0 5.0->200.0 1.0->40.0 |
>4 >4 >35 >50e >14 |
Source: (Aitken et al., 1999; Burch 2000*)
4. Brachyspira pilosicoli
|
|
|
|
||
|
Antimicrobial |
MIC90 |
Range
(μg/ml) |
MIC90 |
Range |
|
Valnemulin Tiamulin Lincomycin Tylosin Dimetridazole Olaquindox Salinomycin |
0.0156 0.0625 128 >128 0.250 - - |
0.0156-1 0.0625-1 0.5-128 2.0->128 0.0625-0.250 - - |
- 2.0 64 >128 - 2.0 1.0 |
- 0.06-2.0 1.0-64 2.0-128 - 0.125-4.0 0.125-1.0 |
Source: (1. Møller et al; 2. 1996 and Cizek et al., 1998)
5. Lawsonia intracellularis
Antimicrobial
|
Minimum
inhibitory concentration (intracellular) (mg/ml) |
Efficacy studies
published**
|
|
Tylosin Tilmicosin Tiamulin Valnemulin* Lincomycin Spectinomycin Apramycin Neomycin Chlortetracycline Penicillin G Amoxycillin Ceftiofur Enrofloxacin |
64 2 4 2 32 32 >128 >128 1 1 1 >8 8 |
Yes, registered, good. No Yes, registered US, good. Yes, good. Yes, good. Yes (L/S), parts EU, good. No Yes, moderate. Yes, good. No. No. No. No. |
Source: (McOrist et al., 1995, 1998*; Burch 2000**)
6. Clostridium perfringens. (
|
Antimicrobial |
MIC50 |
MIC90 |
Range (μg/ml) |
|
Flavomycin |
- |
- |
>128 |
|
Lincomycin |
2 |
256 |
0.12-512 |
|
Penicillin |
0.12 |
0.5 |
0.06-1 |
|
Tetracyclines |
16 |
32 |
0.06-64 |
|
Tiamulin |
- |
- |
0.025-4 |
Source: (Dutta & Devriese, 1980)
Respiratory Infections:
1.a. Mycoplasma hyopneumoniae. (
Antimicrobial |
Source
1 MIC50 |
Source
2 MIC90 |
Source
3 MIC90 |
|
Valnemulin Tiamulin Oxytetracycline Lincomycin Tylosin Tilmicosin Enrofloxacin |
- 0.06 0.125 - 0.125 0.5 - |
0.005 0.078 0.31 0.63 0.31 - - |
0.001 0.05 - - - - 0.01 |
Source: (1. Aitken & Reeve-Johnson,1998; 2.Aitken et al., 1999; 3.Windsor et al., 1996)
1.b. Mycoplasma hyopneumoniae (
|
Antimicrobial |
MIC50 |
MIC90 |
Range |
|
Chlortetracycline |
12.5 |
>100 |
0.78->100 |
|
Oxytetracycline |
0.78 |
6.25 |
0.1-12.5 |
|
Tylosin |
0.025 |
0.05 |
0.0125-0.1 |
|
Acetylisovaleryltylosin |
0.0125 |
0.0125 |
0.0125-0.05 |
|
Tilmicosin |
0.1 |
0.39 |
0.0125-0.39 |
|
Tiamulin |
0.0125 |
0.05 |
0.0125-0.05 |
|
Lincomycin |
0.025 |
0.1 |
0.0125-0.39 |
|
Thiamphenicol |
0.39 |
0.78 |
0.1-1.56 |
Source: (Inamoto et al., 1994)
- Pasteurella multocida and Bordetella bronchiseptica
Antimicrobial |
Canada (1) P. multocida |
UK (2) B. bronchiseptica P. multocida |
|
Ampicillin Ceftiofur Erythromycin Gentamicin Penicillin Spectinomycin Sulfisoxazole Tetracycline Trimethoprim/Sulpha Enrofloxacin |
99 100 76 98 97 96 45 92 98 - |
5 98 0 - 100 - 100 - 0 - 0 - 16 - 100 86 35 93 - 100 |
Source: (1. Laperle et al., 1996; 2. DEFRA, 2001)
3.a. Actinobacillus pleuropneumoniae. (
Antimicrobial |
MIC50 |
MIC90 |
Range |
|
Amoxicillin Amox/Clav. Ceftiofur Danofloxacin Enrofloxacin Florphenicol Linco/Spec. Oxytetracycline Pen/Strep. Thiamphenicol Tiamulin Tilmicosin Trimethoprim/sulpha Tylosin |
0.12 0.12 <0.03 <0.03 <0.03 0.5 4.0 >32 0.25 1.0 16 4 <0.03 16 |
16 0.25 <0.03 0.06 0.06 1.0 16 >32 16 1 16 8 0.12 >32 |
<0.03->32 <0.03-1.0 <0.03-0.06 <0.03-1.0 <0.03-2.0 0.25-2.0 0.06->32 0.25->32 0.03->32 0.25->32 <0.03->32 0.06->32 <0.03-8 16->32 |
Source: (Barigazzi et al., 1996a)
3.b. Actinobacillus
pleuropneumoniae
Antimicrobial |
Sensitivity (%) |
|
|
|
|
|
|
Ampicillin Ceftiofur Ciprofloxacin Erythromycin Gentamicin Penicillin Spectinomycin Sulfisoxazole Thiamphenicol Tetracycline Trimethoprim/sulpha |
82 95 99 97 - 100 52 - 99 - 80 - 70 66 60 - - - 52 74 97 88 |
35 - 76 - 82 - - - 75 23 63 |
Sources: (1. Laperle et al., 1996; 2.DEFRA, 2001; 3. Gutierrez et al., 1995)
- Haemophilus parasuis
Antimicrobial |
Sensitivity (%) |
|
| Italy (1) UK (2) | ||
|
Ampicillin Enrofloxacin Cephalothin Ceftiofur Penicillin Sulphachlorpyridazine Gentamicin Spectinomycin Trimethoprim/sulpha Amikacin Erythromycin Tetracycline Neomycin Apramycin Clindamycin |
100 ≤0.25 100 - 100 - 98 - 98 - 98 - 96 - 96 8.0 (Linco/Spec) 94 0.5 94 - 89 - 85 2.0 79 - 70 8.0 60 - |
|
Source: (1. Trigo et al., 1996; 2. Aitken & Reeve-Johnson, 1998)
5.a. Streptococcus suis (
|
Antimicrobial |
MIC50 |
MIC90 |
Range |
|
Pen/Strep Amoxycillin Ceftiofur Enrofloxacin Florphenicol Linco/Spectin Oxytetracycline Tiamulin Tilmicosin Trimeth/Sulpha Tylosin |
<0.03 <0.03 <0.03 0.5 1.0 2.0 32 1.0 >32 0.25 >32 |
<0.03 <0.03 <0.03 0.5 2.0 4.0 >32 1.0 >32 0.25 >32 |
<0.03 <0.03 <0.03 0.12-0.5 0.5-4.0 0.06->32 0.12-32 <0.03-2.0 4.0->32 <0.03-0.5 0.12->32 |
Source: (Barigazzi et al., 1996b)
5.b. Streptococcus suis. (
|
Antimicrobial |
Sensitivity (%) |
|
Penicillin |
100 |
|
Ampicillin |
100 |
|
Tetracycline |
28 |
|
Trimethoprim/Sulpha |
100 |
|
Ceftiofur |
100 |
|
Enrofloxacin |
100 |
Source: (DEFRA, 2001)
NB. Most of the VLA and DEFRA reports are
from cases that were submitted to the government laboratories and may have been
treated with antimicrobials before submission. The level of resistance may be
higher in these cases.
Oral Antimicrobial Medication Pharmacokinetics in Pigs