There are no registered fluoroquinolone antibiotics available for use in horses. Based on theoretical and observed orthopaedic problems in foals it seems unlikely that any products will be registered in the future. All use in horses is off-label. The two most commonly used drugs are enrofloxacin and ciprofloxacin. Ciprofloxacin is an active metabolite of enrofloxacin.
This class of antibiotic is used frequently in North America in adult horses, often as a first line approach to presumptive or confirmed Gram-negative infections or as prophylaxis. It frequently replaces gentamicin in broad-spectrum combinations with β-lactams, and metronidazole. Recently, it was reported that enrofloxacin was the most commonly prescribed antibiotic in racetrack practice in the US. They are also commonly prescribed for off-label use in the United Kingdom. In Australia it is recommended to use this class of drug in adult horses for multi-drug resistant infections, based on culture and sensitivity, and only if a class of lesser importance is not available. Compounding pharmacies can supply enrofloxacin paste to equine veterinarians in Australia.
Fluoroquinolones should not be used in food-producing animals in Australia. The situation in the US has changed, such that currently there are two injectable fluoroquinolones registered for use in cattle to treat respiratory disease. These are enrofloxacin (Baytril) and danofloxacin (Advocin). Enrofloxacin is also registered for use in the treatment of swine respiratory disease.
Mechanism of action
Fluoroquinolones inhibit bacterial topoisomerases II and IV. The enzyme topoisomerase II was formerly known as DNA gyrase. During bacterial replication the DNA supercoiling is disrupted along with the ability to repair DNA and the cell becomes unviable within 20 minutes. Fluoroquinolones are considered to be bactericidal antibiotics. THe primary routine of clearance is via renal excretion. Consequently, care should be taken in horses with abnormal renal function.
Spectrum of activity
This class of antibiotic is primarily effective against Gram-negative organisms. This includes some common infections of horses caused by Salmonella, E. coli, Enterobacter and Pseudomonas. Fluoroquinolones are also active against Mycoplasma and several Gram-positive aerobic bacteria. They are not effective against obligate anaerobes, although newer generation quinolones do have an anaerobic spectrum of activity. The quinolones are theoretically synergistic with β-lactams, aminoglycosides, and metronidazole.
Side-Effects
Both enrofloxacin and ciprofloxacin have been associated with cartilage damage in foals. This effect is accentuated by weight bearing. Enrofloxacin given to healthy foals (10 mg/kg PO SID for 5 days) produced synovitis, thickening of joint capsules and severe cartilage erosions. The effect on foetal cartilage was recently examined and the authors concluded that although osteochondral lesions were detected in foals there was no difference between foals from untreated mares and from mares that received enrofloxacin at either 7.5 or 15 mg/kg daily for 14 days, beginning at 280 days gestation. The age when it is considered to be safe for adult horses is not known with some recommending avoidance in horses less than 4 years of age. Many practices in the US recommend restricting use in horses less than 2 years of age.
Fluoroquinolones also negatively affects equine tenocyte proliferation. There is also growing evidence that fluoroquinolone treatment causes tendinopathy in adult humans, which can result in tendon damage up to 6 months after administration. Adult horses have developed desmitis and tendinitis on enrofloxacin although this appears to be rare, and possibly associated with higher dose rates.
Intravenous enrofloxacin caused changes in gut flora, with a decrease in the abundance of Fibrobacteres and an increase in the abundance of Lachnospiraceae. Coincident with these changes was an increase in potentially pathogenic Clostridia. A decrease in Fibrobacteres has been associated with Antibiotic-induced diarrhoea in horses. This family of bacteria is important in digesting plant cell wall polysaccharides into the important short chain fatty acids (acetate, propionate, butyrate). A reduction in this class leads to proliferation of bacteria that metabolize dietary starch into lactate. This includes the Lachnospiraceae, as well as Streptococcus and Lactobacillus species. Lactate causes a reduction in gut pH, which can further impact microbial and gut wall health. The implications of these changes is not known, although diarrhoea has been a reported, but rare side-effect of enrofloxacin in some horses.
Dosing
Dosing information is intended for use by registered veterinarians or veterinary nurses. Equiimed assumes no responsibility for the information detailed below. Equiimed shall not be liable for any damages resulting from reliance on any information provided below, or by reason of any misstatement or typographical errors. Ultimately veterinarians should consult information provided by the manufacturer prior to use.
Tags: Pharmacology