Effective Ileitis Treatment With Pharmasin® By Consideration Of PK/PD Knowledge
Ulrich Klein
Porcine proliferative enteropathy (ileitis) is a common and widespread infection in pigs worldwide. The disease is caused by Lawsonia intracellularis, an anaerobic obligate intracellular bacterium infecting the small intestine and infrequently also the large intestine of pigs. In its acute form, it can cause mortality (finishing pigs, gilts), and in its chronic form leads to soft faeces, depression and unevenness of growth (growers, finishers).
Reported ileitis prevalence on farms is high with significant differences between countries. On these farms, a high number of pigs are exposed to L. intracellularis infection as shown in Table 1.
Table 1. Ileitis - a truly global challenge1,2
Optimising the treatment of ileitis requires information on the mechanisms involved in the effect of the antibiotic (pharmacodynamics, PD) and the evolution of the antibiotic concentration in the pig (pharmacokinetics, PK).
The major indicator of the effect of antibiotics is the minimum inhibitory concentration (MIC) which provides information about the susceptibility of the pathogen against the antibiotic. However, the clinical outcome is determined not only by the MIC value but is also dependent on the PK behaviour and characteristics of the antibiotic administered.
In the case of ileitis infections, there are two major intestine regions of significance:
- the lower small intestine (ileum)
- the large intestine (colon)
Pharmacokinetic studies conducted in pigs based on feed and water medication of Pharmasin® (tylosin) indicate that high tylosin concentrations are achieved in the colon and ileum at treatment dosage (Table 2).
Table 2. Tylosin oral pharmacokinetics - feed and water medication3,4
The combination of PK and PD data is a powerful tool to elucidate the therapeutic effect of Pharmasin® in the treatment of ileitis infection. As shown in Figure 1, tylosin concentrations in the ileum achieved after oral therapeutic administration exceed the intracellular MIC values determined in in vitro MIC studies. Consequently, a high therapeutic effect of Pharmasin® can be expected in the case of ileitis treatment at the registered dose.
Figure 1. Tylosin PK/PD relationships for L. intracellularis strains (EU, US, Thailand, Brazil)
Figure 1 is based on:
- Intracellular MIC values for L. intracellularis isolates originating from the EU/US where each strain was tested twice5 and Brazil/Thailand where each strain was tested once6.
- Tylosin concentrations in ileum content following oral administration at the following registered dose:
- Pharmasin® premix at 4-5 mg tylosin phosphate/kg bodyweight/day: 14.2 µg/g (B)
- Pharmasin® water soluble granules at 5 mg tylosin tartrate/kg body weight/day: 12.03 µg/g (A)
- Pharmasin® water soluble granules at 10 mg tylosin tartrate/kg body weight/day: 24.05 µg/g (C)
Conclusion
The PK properties of Pharmasin® (tylosin) are characterised by its high presence in the colon and ileum of pigs and by accumulation of tylosin into gut enterocytes, the preferred place of residence of L. intracellularis. Tylosin PK/PD relationship data are a powerful tool to set tylosin dosing regimens against ileitis. The available PK/PD data verify why high efficacy of this therapeutic drug can be expected in case of ileitis treatment and why it is the most commonly used antibiotic product for ileitis treatment in the field.