Chapter 8 – Macrolides

Overview/Relevance

Macrolides have a similar mode of action to lincosamides and pleuromutilins. Several macrolides are commonly used in swine medicine. Tylosin has been used as a growth promoter as well as for the control of proliferative enteritis and swine dysentery. Its efficacy is limited today by numerous resistances. Tilmicosin needs to be used orally in swine, IM injection can be fatal to pigs. Tulathromycin is usually used as a second-line antimicrobial due to its elevated cost.

Useful molecules to know in swine medicine:

• Tylosin
• Tulathromycin
• Tilmicosin
• Tylvalosin

Mechanism of Action

Macrolides bind to the 50S subunit of the ribosome and stop the addition of new amino-acids, inhibiting protein synthesis.

Check your learning: Macrolides and Mechanism of Action

Spectrum

Macrolides have a fairly large spectrum on both aerobic and anaerobic Gram positive and Gram negative bacteria as well as Mycoplasma spp. They are also active against Spirochetes such as Brachyspira spp. which made them a great tool to fight against enteric disorders such as swine dysentery or proliferative enteritis.

Absorption

Macrolides are lipid soluble and basic molecules that are easily absorbed in the intestinal tract, giving it a good bioavailability

Distribution

Macrolides have an excellent tissue penetration and a large Volume distribution.

Elimination

Macrolides are eliminated through the bile more than through the urine. Tilmicosin and tylosin tend not to be transformed in the liver. Orally administered, tilmicosin has a half-life of 25 hours. Tulathromycin is slowly eliminated with a half-life of 90 hours. This is an interesting property to treat food animal species.

Adverse effects

Tylosin is a relatively safe drug but it can cause erythema of the perianal area and reversible mild rectal prolapse. Tilmicosin can be fatal to swine if injected IM at dose 10-20mg/kg, through its cardiovascular toxicity.

Resistances are common against macrolides and in swine medicine, especially against tylosin. The resistance genes are mobile and can be shared horizontally between bacteria. Additionally, some resistance mechanisms can be effective against various molecules in the same antimicrobial family but also against several families.

Because of their similar mode of action, amphenicols, lincosamides, pleuromutilins and macrolides should not be used concomitantly as they would compete against each other to bind on the 50S ribosomal subunit.