Tildipirosin is a new-generation animal-exclusive macrolide antibiotic, originally developed by Intervet International BV as a derivative of tylosin. This broad-spectrum antimicrobial is effective against Gram-positive bacteria and certain Gram-negative pathogens, particularly those causing respiratory diseases in swine, cattle, and sheep. With high morbidity rates leading to growth retardation, reduced feed efficiency, and mortality, respiratory infections significantly impact farm profitability. Tildipirosin offers key advantages:

• Species-specific (veterinary use only)

• Low dosage requirement

• Single-dose efficacy

• Rapid absorption

• Extended elimination half-life (up to 9 days)

• High bioavailability

• Low residue levels

• Proven safety profile

1. Mechanism of Action

Tildipirosin binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting protein synthesis. Its unique dual-piperidine configuration enhances activity compared to tylosin/tilmicosin by:

• 20-piperidine directing lumenal entry to disrupt nascent peptides.

pH-Dependent Activity:

• 3 basic amino groups enable pH-responsive charge states.

• Alkaline conditions ↑ antibacterial activity (enhanced membrane penetration).

• Acidic conditions ↓ activity (protonation reduces lipid solubility).

Anti-inflammatory Effects:

• Suppresses pro-inflammatory cytokines, phospholipase A2, and leukotrienes.

• Modulates macrophage/neutrophil responses.

2. Antimicrobial Spectrum

Resistance Notes:

• Enterococci/Streptococci: Intrinsically resistant.

• Mutant M. bovis: 23S rRNA (Domain II/V) mutations confer macrolide resistance.

3. Pharmacokinetics

Key Parameters (Swine, 4 mg/kg IM):

• T~max~: <1 hr

• C~max~: 0.7 μg/mL

• t~1/2~: 9 days

• Bioavailability: 85.5% (IM), 109% (IV)

• Tissue Distribution:

  • Lung/Bronchi: 681× plasma concentration

  • Tonsils: 75× plasma at 24h

Dosing for Respiratory Pathogens:

• P. multocida: 4.12 mg/kg (preventive), 6.35 mg/kg (therapeutic)

• H. parasuis: 2.07 mg/kg (preventive), 4.17 mg/kg (therapeutic)

4. Clinical Applications

Swine Respiratory Disease Trials:

Notable Findings:

• Prevents M. haemolytica in calves (10-day pre-challenge).

• Treats ovine digital dermatitis (spirochetes).

• Improves weight gain (+13%) in Holstein heifers.

5. Safety & Residues

• Safe at 4–12 mg/kg (swine/cattle).

• 5× overdose: Hepatorenal/cardiac toxicity.

• Withdrawal Period: 10 days (HPLC-MS/MS validated).

• EU MRLs (2014):

  • Muscle: 50 μg/kg

  • Liver: 1000 μg/kg

6. Conclusions

Tildipirosin’s single-dose efficacy, prolonged tissue persistence, and superior clinical outcomes position it as a first-line option for livestock respiratory disease control. Its molecular diagnostics-compatible resistance profile further supports judicious use in antimicrobial stewardship programs.