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HEAL ▶▶▶TH


Table 2 – Country-specific MIC results (µg/ml) for B. hyodysenteriae isolates for commonly used antimicrobial agents.


Bacteria No isolates Tiamulin


AST method MIC50 MIC90


Belgium 2010-2015 Brazil 2012-2013 Germany 2003-2012


30 BD


22 BD


103 BD


Japan 2009 29 AD


Poland 2006-2010 Spain 2008-2009


21 BD


87 BD


Switzerland 2010-2017 51 BD


USA 2009-2014 Italy 2009


40 BD


30 BD


Tylvalosin MIC50


MIC90 4 16


Tylosin MIC50


MIC90


>128 >128


Lincomycin MIC50


MIC90


MIC range MIC range MIC range MIC range 0.5 4


16 32


≤0.004-8 8 8


≤0.063->8 0.5 8.0


≤0.063->64 1.56 6.25


0.1-12.5 0.5 1.0


0.25-1 16


≤0.063-8 <0.031 <0.031


2-32 4 8


<0.031-0.25 0.125-64 ≤0.063 2


≤0.063-8 0.5 1.0


0.063-2.0


≤0.125-32 16 32


1-32


2->128 >128 >128


4->128 >128 >128


25 50


0.39-100


≤0.125->128 >100 >100


<0.1->100 >128 >128


16>128 >128


16->128 >128 >128


1->128 >128 >128


≤2->128 128 128


64-128


0.25-64 64


>64


2->64 16 32


≤0.063->64 3.13 12.5


0.78-25 16 16


2-32


1 4 >128 16 8


>64


1->64 16 32


0.25-64 16 32


≤0.5->64 16 64


4-64 AST: Antimicrobial susceptibility testing; BD: broth microdilution method; AD: agar dilution method.


Table 3 – Colon and ileum concentration (µg/g) of different antibiotics used for enteric infection treatment (oral application).


Antimicrobial Dose (ppm, mg/kg bw)


Tiamulin (Vetmulin) 110 220 110


Lincomycin 220 (11 mg/kg bw) Tylosin (Pharmasin) 250 mg/g Tylvalosin E = estimate References available on request. 16 ▶PIG PROGRESS | Volume 36, No. 4, 2020


premix (10 mg/kg bw) 100 200


Colon content


concentration (CCC) 2.84 8.05 34.5


101.01 89.4


11.3 E (>5-17.5) 22.5 E (>10-35)


Ileum content)


concentration (CCC) 0.82 2.33


10.01 25.05 31.4


3.28 E (>1.45-5.08) 6.53 E (2.9-10.15)T


antibiotics. The relation allows vets to assess if effective ther- apeutic concentrations can be achieved at the ileum and co- lon infection site. In Table 3 the colon content concentration (CCC) and ileum content concentration (ICC) of different anti- biotics achieved after in-feed treatment at registered dose levels is summarised. The published data show a rather linear relationship be- tween the in-feed concentration and found CCC and ICC of the antibiotics. Tiamulin achieves relatively low concentra- tions in the colon and ileum in comparison with lincomycin and tylosin. Concentrations of tylvalosin in the colon and ileum are in between after in-feed medication.


PK/PD profiles for Lawsonia intracellularis PK/PD analysis demonstrates differences between the three drugs and their likely potential to inhibit ileitis infections. A strong treatment effect against ileitis can be expected at ICC of the drug after oral administration at or above the in- tracellular MICs. This is the case for tiamulin (tiamulin ICC 2-18 times above the MIC) and for tylosin (tylosin ICC 1-125 times above the MIC). In the case of lincomycin, a prediction of the treatment effect cannot be given after oral administration based on much lower lincomycin ICC versus the determined lincomycin MICs.


PK/PD profiles for Brachyspira hyodysenteriae PK/PD differences of the four drugs are important to consid- er for the decision on what antibiotic to select for SD treat- ment. For prediction of successful treatment against SD, the CCC of the drug needs to be at or above the MIC50


and MIC90


values. This is the case for tiamulin at both dosage levels tested. High lincomycin MIC50


and MIC90 values predict a therapeutic


effect only at the higher tested dose. A treatment effect of tylosin is unlikely based on tylosin MICs greatly in excess of tylosin CCCs achieved. Tylvalosin CCCs at two treatment lev- els are in between MIC50


and MIC90 values. A therapeutic effect is likely to be achieved at lower MICs.


Conclusions Susceptibility testing, knowledge of antibiotic pharmacoki- netics and targeted use of antibiotics are effective tools to limit development and expansion of AMR. Antibiotic drug PK/PD profiles help to identify the best dosing regimes for enteric infection treatments. These PK/PD concepts are the basis for therapeutic success, for distinct reduction of B.h. and L.i. levels to avoid SD/PPE reinfections in the next pro- duction phases and for dose optimisation which helps to prevent therapeutic failures.


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