Bacterial Infectious Disease Treatment in Ferrets and Rabbits

Karen L. Rosenthal, DVM, MS, Diplomate ABVP-Avian
Director, Special Species Medicine
Clinical Studies-Philadelphia
University of Pennsylvania
School of Veterinary Medicine
Philadelphia, PA, 19104

Thousands of doses of antibiotics are dispensed each year for ferrets and rabbits. Importantly, not one single dose of any of these antibiotics is approved for the animals that are receiving the medication. Presently, there are no antibiotics approved by the FDA in the United States for the small mammal pets classified as minor species. It is likely owners of these animals do not realize the antibiotics they are giving to their small mammal pets are not approved for their pets. Although, this does not change the fact that antibiotics are important medications for ferrets and rabbits, it is best that owners be informed of this information.

An important consequence of the lack studies to gain approval is that there are few pharmacokinetic investigations of antibiotics in ferrets and rabbits. Veterinarians do not have studies directing them to either dose or length of treatment or frequency of administration of antibiotics in ferrets and rabbits. There are no drug company brochures guiding veterinarians as to the indications of certain antibiotics in ferrets and rabbits. Veterinarians who treat ferrets and rabbits must rely largely on empirical data and anecdotal information when using antibiotics in these animals. It is therefore not surprising if antibiotic treatment failure occurs in these patients when the very basics of antibiotic administration are unknown.

The principles of antibiotic use in dogs and cats apply similarly to ferrets and rabbits. An important difference to consider is that there are fewer safe antibiotics to use in rabbits than there are in dogs and cats. For example, amoxicillin, a benign drug in most animals, can cause a fatal enterotoxemia in rabbits. Ideally, before instituting antibiotics, obtain a culture and a minimum database. Choose the antibiotic based on those results. Institute empirical antibiotic treatment if a culture cannot be obtained or before results are known. Whenever antibiotics are used empirically, consider four-quadrant coverage. To accomplish this, choose drugs that are effective against aerobic, anaerobic, gram positive and gram negative organisms. There are seven questions to consider before empirical antibiotic treatment begins in a ferrets and rabbits:

1.  What organ system is involved?

2.  Is the infection acute or chronic?

3.  What is the most likely pathogen at the infection site?

4.  What antibiotic is best against that pathogen?

5.  How much antibiotic is needed at the infection site?

6.  What is the dose and route of administration of that antibiotic?

7.  Is the antibiotic safe for rabbits and rodents?

Before an antibiotic is chosen, identify the organ system involved. This can be challenging in rabbits. It may not be apparent if the site of infection is primary or secondary. For example, jaw abscesses in rabbits are common. Yet, very few jaw abscesses are caused by puncture wounds to the face. Jaw abscesses are frequently due to organisms that travel from other sites. One must consider where are those other sites and therefore, what other organ systems are involved? Treating a jaw abscess without recognizing that this is not an isolated event will probably lead to antibiotic treatment failure.

In rabbits, one must determine if the bacterial disease is the result of an acute infection or an acute manifestation of a chronic infection. For example, a pet rabbit exhibits signs of "snuffles" at age three. Is this because the rabbit recently developed upper respiratory bacterial disease or because a chronic pasteurellosis infection is only now becoming apparent? Determination of acute or chronic bacterial disease is imperative as this dictates prognosis, treatment length, and choice of antibiotic.

In rabbits, it is common to attribute all infections to Pasteurella multocida but numerous species of bacteria are cultured routinely from rabbits. Before culture results are known, obtain a gram stain of the infected area to potentially identify the organism. Some selected bacterial species known to infect rabbits include pathogenic species of staphylococcus and streptococcus, Klebsiella, Proteus, Pseudomonas, Listeria, Actinomycoses, and Actinobacillus.

The best antibiotic to use is based not only on the spectrum of activity of the antibiotic but also on the safety of that antibiotic in rabbits. It is always preferred to use an antibiotic that has the least likelihood of inciting gastrointestinal disease. Some of the safer drugs include trimethoprin sulfas, Quinolones, chloramphenicol, aminoglycosides, and metronidazole. Antibiotics that are intermediate in their ability to incite gastrointestinal disease include parenteral penicillin, oral or injectable cephalosporins, tetracycline, and erythromycin. Antibiotics that are highly likely to cause gastrointestinal dysbiosis include amoxicillin, ampicillin, clindamycin, and lincomycin. They suppress the normal gastrointestinal flora allowing other flora to proliferate leading to deleterious changes. The abnormal flora changes the pH which increases volatile fatty acid production, thereby further suppressing the growth of normal bacteria. Eventually, enteritis develops and ultimately the production of toxins from Clostridium, specifically Clostridium spiroforme (iota toxins) leads to enterotoxemia.

Treat antibiotic-induced enteritis and enterotoxemia aggressively to save the patient. Stop the antibiotic. Some recommend the use of metronidazole at 20 mg/kg q12 hours to decrease the amount of clostridium. Give intravenous or subcutaneous fluids and nutritional supplementation with high fiber foods. Some advocate using cholestryramine to prevent death from the iota toxins. It has been shown experimentally to work by theoretically binding bacterial toxins and has been suggested at a dose of 2g/20 cc of water q24 hours by gavage.

The amount of antibiotic needed at the infected site is difficult to determine in rabbits because of the caseous pus they form and the walled off abscesses that are impenetrable to many antibiotics. Clearly, for abscesses, it is best to combine antibiotic therapy with wound debridement and daily flushing to increase the chance of successful therapy.

The administration for most antibiotics in rabbits is based on clinical experience. Exotic animal formularies list dose ranges, dose frequency, treatment length and methods of administration. In rabbits, consider the stress of administration when determining how the patient is to receive the medication. Do not give or apply combination antibiotic and steroid preparations to rabbits. Antibiotic administration in the drinking water rarely allows the drug to reach effective serum concentrations. And if the drinking water develops an undesirable taste from the antibiotic, the patient could stop drinking and dehydrate.

Finally, after considering the first six criteria, determine if the chosen antibiotic is safe for rabbits. Not all rabbits develop gastrointestinal disease from the more dangerous antibiotics. And not all small mammals die from antibiotic-induced gastrointestinal disease. But the risk of disease can be greatly lessened when the appropriate treatment is selected.

Guidelines for antibiotic use in ferrets are simpler to follow than it is in rabbits. Ferrets, since they are carnivores, have a gastrointestinal system more akin to dogs and cats than to rabbits. Usually, the antibiotics that are safe to use in dogs and cats are safe to use in ferrets. No antibiotic pharmacokinetic studies have been performed in ferrets so drug dose, treatment length, and frequency are based on clinical experience and extrapolated from other species. In ferrets, the most appropriate antibiotic based on culture results can be used without regard to serious gastrointestinal upset.

Antibiotic administration in ferrets and rabbits includes the parenteral, enteral, and topical routes. Parenteral routes include intramuscular, subcutaneous, intraperitoneal, intravenous or intraosseous. Because of their size, the intramuscular route is rarely used for an extended period of time in ferrets and rabbits. The intravenous or intraosseous routes are reserved primarily for the most severe cases of bacterial disease. The subcutaneous route of antibiotic administration is the most frequently utilized parenteral route of administration in ferrets and rabbits. In ferrets and rabbits, the enteral route is used extensively, especially with at home administrated antibiotics. Antibiotics are given by syringe or in the food. It is difficult to administer antibiotics in pill form to most small mammals. Rabbits may take medication mixed in jams or jellies. Use the topical route of drug administration for superficial infections in ferrets and rabbits. This should be done cautiously if the topical antibiotic ingredient could cause dysbiosis if ingested by the patient.

The ideal antibiotic to use in ferrets and rabbits is easily administered, bactericidal and does not cause gastrointestinal disease. These are some of the more common drugs used with ferrets and rabbits. Use antibiotics such as penicillin with caution in rabbits. Oral penicillin is associated with gastrointestinal disease in this species. Injectable penicillin is safer to use and is recommended at 40-80,000 u/kg IM. Trimethoprin sulfa drugs are commonly used in ferrets and rabbits and appear to be safe. Use these drugs at 30 mg/kg q12hrs PO. Caution is recommended in patients with urinary tract disease.

Since aminoglycosides are potentially nephrotoxic in ferrets and rabbits, use this class of drugs with discretion. Also, these antibiotics poorly penetrate abscessed areas and may be a poor choice for many rabbit infections. Use amikacin at 8-16 mg/kg q24hrs IM/IV.

The most commonly used class of drugs in ferrets and rabbits are the quinolones. This antibiotic group is safe, can be given orally, and is effective against Pasteurella and other serious gram negative infections. Enrofloxacin is used at 10-30 mg/kg q24hrs IM/SC/PO.

Metronidazole is used for anaerobic infections. Use this drug at a dose of 20 mg/kg q12-24hrs PO. The incidence of anaerobic infections in ferrets and rabbits is unknown.

A new concept in drug administration is called pulse therapy. This treatment involves once a day drug administration rather than multiple daily dosing. Drugs that are effective in pulse therapy have a "post-antibiotic effect". They are still effective even after their concentrations decrease. Also, drugs that are used for pulse therapy have their best effect at a high dose for a limited time. This is opposed to the classes of drugs that are more effective at a steady state. Penicillins are more effective at steady state concentrations. Quinolones and aminoglycosides are more effective in pulse therapy. Pulse therapy is ideally suited for ferrets and rabbits. Drug administration can be challenging in these small animals and stressful to the patient. Once a day administration is therefore advantageous. For this reason, selection of a quinolone antibiotic in small mammals is a rational choice based on safety, spectrum of activity, and once a day administration.