TILMODAD

Indications

• Bacterial respiratory infections in cattle
• Bacterial respiratory infections in swine
• Mycoplasma infections

Dosage

Children: Refer to BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to BNF for specific adult dosing recommendations.

Mechanism of action

Tilmicosin exerts its antimicrobial effect by reversibly binding to the 50 S subunit of the bacterial ribosome. This binding inhibits protein synthesis by preventing the translocation process necessary for elongation of the peptide chain. Tilmicosin is particularly effective against rapidly dividing bacteria and mycoplasmas, and its activity is enhanced in higher pH conditions.

Pharmacodynamics

As a macrolide antibiotic, tilmicosin demonstrates bacteriostatic activity, meaning it inhibits the growth of bacteria rather than killing them outright. It has a broad spectrum of activity against gram-positive bacteria and mycoplasma, while its activity against gram-negative organisms is limited to specific strains. Additionally, macrolides like tilmicosin may modulate host immune responses, affecting the production of inflammatory mediators such as nitric oxide and cytokines.

Pharmacokinetics

Tilmicosin exhibits variable absorption and distribution characteristics, often accumulating in lung tissue, which is beneficial for treating respiratory infections. It has a relatively long half-life, allowing for less frequent dosing. The drug is metabolized in the liver, and the majority of its metabolites are excreted via the kidneys. Its pharmacokinetic profile is influenced by the pH of the environment, with higher pH levels enhancing its activity.

Pregnancy

There is limited data on the safety of tilmicosin during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether tilmicosin is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Injectable solution

Mechanism of action

Tilmicosin has in vitro activity against gram-positive organisms and mycoplasma and is active against certain gram-negative organisms, such as Hemophilus somnus, Mannheimia (Pasteurella) hemolytica, and Pasteurella multocida. However, M. hemolytica is more sensitive than P. multocida to tilmicosin. Other gram-negative organisms tested, including Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella, and Serratia species, are very resistant to tilmicosin. Some strains of Actinomyces also are extremely resistant to tilmicosin. The antimicrobial mechanism seems to be the same for all of the macrolides. They interfere with protein synthesis by reversibly binding to the 50 S subunit of the ribosome. They appear to bind at the donor site, thus preventing the translocation necessary to keep the peptide chain growing. The effect is essentially confined to rapidly dividing bacteria and mycoplasmas. Macrolides are regarded as being bacteriostatic, ... . Macrolides are significantly more active at higher pH ranges (7.8-8). /Macrolides/ Macrolides have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. /The authors/ examined the in vitro effect of the macrolides tilmicosin and tylosin, which are only used in the veterinary clinic, on the production of nitric oxide (NO), prostaglandin E2 (PGE2) and cytokines by lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse peripheral blood mononuclear cells (PBMCs). Compared with 5 ug/mL, tilmicosin and tylosin concentrations of 10 ug/mL and 20 ug/mL significantly decreased the production of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), PGE2, NO, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6, and increased IL-10 production. Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression were also significantly reduced. These results support the opinion that macrolides may exert an anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process.