Chapter 5 – Fluoroquinolones

Overview/Relevance

There are fourth generations of fluoroquinolones. The latest molecules are limited to human medicine and cannot be used in veterinary medicine. Enrofloxacin is the molecule most used in swine medicine. It belongs to the second generation (Group II) of fluoroquinolones and is considered a critically important antimicrobial for human medicine. Therefore, all extra-label use in food animal species is absolutely prohibited.

Useful molecule to know in swine medicine:

• Enrofloxacin → Extra-label use is prohibited!

Mechanism of Action

Fluoroquinolones acts on the enzymes (all act on the gyrases and some on the topoisomerases) coiling bacterial DNA. This means that the DNA cannot transition back and forth from its relaxed form to its double-helix structure. This impairs replication and ultimately, both DNA strands get broken.

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Spectrum

Fluoroquinolones are extremely active against Gram – aerobic organisms but they efficacy is limited against Gram + bacteria. Fluoroquinolones can also be used against Mycoplasma spp.

Absorption

Fluoroquinolones have a good bioavailability and are well absorbed in the stomach of mono gastric species. Additionally, they have both an acidic and basic units so they are amphoteric and water soluble, and need to enter bacteria through porines.

Distribution

Fluoroquinolones have a large volume distribution and tends to accumulate in the cells cytoplasm. Because of this propriety, dosage needs to be increased to be able to reach Cmax > MIC. They also have the ability to reach the cerebro-spinal and synovial fluids.

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Elimination

There is some phase I and phase II metabolism occurring in the liver. Eventually metabolites are excreted in the kidney but the half-life is relatively long, which means that the animals need to be treated only once a day.

Adverse effects

Fluoroquinolones’ toxicity is rare in swine.
Some bacteria developed resistance to fluoroquinolones by modifying the enzymes targeted by the antimicrobial. The gyrase and/or topoisomerase is modified so that the fluoroquinolone cannot bind to it. Another type of resistance can be established by increasing the number of efflux transporters on the bacterial membrane.