Author: Ronald K. Tessman, DVM, PhD, DACVIM, DACVPM, Beef Cattle Technical Consultant, Elanco Animal Health

Maintaining cattle health is a constant challenge. Beef producers understand that managing disease is key to maintaining healthy cattle and protecting profitability potential. Informed, knowledge-based decisions about antimicrobials coupled with optimized management and animal husbandry can serve to ensure continued antimicrobial efficacy and utility.

To ensure that medications critical to disease management protocols continue to effectively treat diseases such as Bovine Respiratory Disease (BRD) in cattle, resistance management must remain top-of-mind.

The first step to maintaining the efficacy of these medically important medications is to understand the mode of action of a product’s active ingredients.

How Macrolides Work

The macrolide mode of action, which includes tulathromycin and tilmicosin, is a class of antibiotics that inhibit bacterial protein synthesis, preventing bacterial growth. The macrolide mode of action binds to the 50s ribosomal subunit of bacteria, disrupting the translation of mRNA and protein production. In general, macrolides are time dependent, which means to be effective they require concentrations to be above the minimum inhibitory concentration (MIC) for an extended time.

In most instances, macrolides are considered bacteriostatic, meaning that they control the growth of a bacterial infection, allowing time for the animal’s natural immune system to respond and overcome the infection. There are notable, well-established exceptions at certain concentrations when specific bacteria macrolides are considered bactericidal.

How Fluoroquinolones Work

Fluoroquinolones attack the enzymes that control DNA replication and transcription, DNA gyrase and Topoisomerase IV. Fluoroquinolones are concentration dependent and bactericidal. Meaning the activity is dependent on the highest concentration achieved above MIC levels, rather than the length of time above MIC. The bactericidal component that kills the bacteria relies on the animal’s system to clear the dead bacteria.

How Pradofloxacin Differs

Traditional fluoroquinolones, such as danofloxacin, only target DNA gyrase in gram negative organisms.

In comparison, pradofloxacin is a third-generation fluoroquinolone that targets DNA gyrase and attacks Topoisomerase IV in the same organism, with the same efficiency. That translates to having two targets in the same pathogen causing the infection. Pradofloxacin reaches maximum concentrations within 45 minutes of injection, much faster than the other fluoroquinolones. And it has dramatic killing properties, killing 99% of organisms exposed in a laboratory test within five minutes.

Pradofloxacin also quickly achieves high concentrations above another laboratory measure - mutant prevention concentration (MPC).  MPC is a laboratory measure, much like MIC. However, with MPC, you are testing a billion organisms, rather than the 100,000 being tested with MIC, better reflecting what is happening at the infection level. Because pradofloxacin reaches high above-MPC concentrations very quickly, we reduce the probability for choosing for resistant bacteria. Having those two targets of activity also results in a more potent active ingredient, and therefore enhanced in-vitro killing.

Why it Matters

Macrolide antimicrobial concentrations must remain above the minimum inhibitory concentration level for an extended period to be effective. Fluoroquinolones only need to reach concentrations above MIC for a short period to have the same effect. Pradofloxacin has the advantage of quickly reaching therapeutic levels, showing tremendous bacterial killing in laboratory tests. When treating sick animals, we can take advantage of these attributes by addressing the bacterial infection quickly and efficiently. The additional benefit of reducing the probability of choosing for resistant bacteria aids in resistance management.

In summary, pradofloxacin acts quickly and efficiently to address sick animals. Because it is concentration dependent, it doesn't have to last for a long time. Pradofloxacin attacks two separate targets in the disease pathogen’s DNA, which improves product efficacy and benefits resistance management.

Visit Elanco.com or talk to your veterinarian or local Elanco representative about how Pradalex can help control BRD in cattle.

Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Not for use in animals intended for breeding greater than 1 year of age because the effects of Pradalex on bovine reproductive performance, pregnancy, and lactation have not been determined. Not for use in beef and dairy calves less than 2 months of age, and veal calves; a withdrawal period has not been established for this product in pre-ruminating calves. See package insert for additional safety information.

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