Chapter 11 – Tetracyclines
Overview/Relevance
Tetracyclines are widely used in swine medicine especially for respiratory challenges. Their broad spectrum and low cost makes them a treatment of choice. However, resistances against tetracyclines have been developing over the years.
Useful molecules to know in swine medicine:
- Chlortetracycline
- Oxytetracycline
Mechanism of Action
Tetracyclines diffuse through the outer membrane of the bacteria and is then actively transported through the inner membrane. They reversibly bind to the 30S ribosomal subunit and stop the creation of the amino-acid chain, inhibiting protein synthesis.
Check your learning: Tetracyclines and Mechanism of Action
Spectrum
Tetracyclines tend to have a broad spectrum. They are efficacious against Gram + and Gram – bacteria, aerobic and anaerobic, Mycoplasma spp. and a variety of less common pathogens such as Toxoplasma gondii.
Absorption
Tetracyclines have a poor per os bioavailability in swine. In addition to that, tetracyclines reacts with cations such as Ca2+ to form precipitates. Therefore, a diet rich in milk or derived products will significantly lower intestinal absorption. Moreover, tetracyclines are time-dependent antibiotics so increasing the concentration in the feed will not increase efficacy.
Distribution
Oxytetracycline and Chlortetracycline are water-soluble and therefore have a lower volume distribution than lipid-soluble doxycycline.
Metabolism and elimination
Most water-soluble tetracyclines are excreted unchanged in the urine and to a lesser extent in the bile. Tetracyclines under enterohepatic recycling which means that some of the molecules absorbed by the intestines are directed to hepatic cells and are then excreted in the bile without being metabolized. They then go back to the intestinal lumen where they get absorbed for the second time. This propriety extends the half-life of the molecules dramatically (up to 10 hours). However, this property is less true for chlortetracycline which gets broken down in alkaline environments.
Check your learning: Tetracyclines and Metabolism and Elimination
Adverse effects
Tetracyclines have a preference for prokaryotic organism thanks to the active absorption mechanisms that are not present in eukaryotic cells (host cells).
Resistances against tetracyclines are common, especially in Escherichia coli, Pasteurella multocida, Salmonella spp. This is due to the heavy use of these antimicrobials in the 1950s until the late 1980s. Indeed, tetracyclines have a broad spectrum, low toxicity and are relatively inexpensive, making them an antimicrobial of choice in food animal species.
Synergies
Tetracyclines have a synergistic effect with tiamulin. This combination is commonly used in swine medicine to treat respiratory disorders. They also have synergistic effects with tylosin to treat Pasteurella spp. Considering that resistances are common in this bacterial species, this combination can be interesting to consider.