- Many pet rabbits carry Pastuerella multocida, although Pasteurella-free rabbit colonies are common in research settings.
- Pasteurella multocida is the most common cause of respiratory disease in rabbits.
- Pasteurellosis primarily causes rhinitis in rabbits, however disease may also present as lower respiratory tract infection, otitis media, dacryocystitis and conjunctivitis, abscesses in various tissues, reproductive tract disease, and septicemia.
- Diagnosis of pasteurellosis relies upon clinical signs as well as laboratory testing. Cytology may demonstrate many rod-shaped bacteria and degenerative heterophils. Definitive diagnosis relies upon culture and/or PCR testing.
- For management of rhinitis, conjunctivitis, or dacrocystitis, pair systemic antibiotics with topical treatment such as ophthalmic drops and nasolacrimal flushing whenever possible.
- Most strains of Pasteurella spp. are sensitive to chloramphenicol, tetracyclines, and sulfonamides. Some strains are sensitive to penicillin, higher generation macrolides, such as azithromycin, and fluoroquinolones like enrofloxacin.
- Medical therapy alone is unlikely to be effective for treatment of abscesses. Surgical debridement, including removal of the entire abscess capsule, is recommended whenever possible.
- Antibiotic impregnated polymethylmethacrylate beads can be implanted into abscess cavities before closure and are especially helpful with bone or dental abscesses, in which resection options are limited.
Pasteurellosis is a common disease affecting pet rabbits (Oryctolagus cuniculus). Pasteurellosis can have a variety of clinical presentations including rhinitis, pneumonia, otitis, pyometra, osteomyelitis, and abscess. Disease can be acute or chronic, with some rabbits becoming asymptomatic carriers after resolution of clinical signs. The following review article will address the most common disease processes caused by Pasteurella multocida in the rabbit as well as the microbiology, diagnosis, and treatment of pasteurellosis.
Pasteurella multocida is a non-motile, bipolar staining, non-spore-forming,
Gram-negative coccobacillus. This facultative anaerobe is a member of the family Pasteurellaceae. Currently this genus is divided into three subspecies: P. multocida subsp. multocida, P. multocida subsp. septica, and P. multocida subsp. gallicida. Several bacteria belonging to Pasteurellaceae are potential pathogens in the rabbit. In a recent survey of rabbit populations with pasteurellosis by Stahel et al, 82% of isolates were characterized as P. multocida subsp. multocida. Of the remaining isolates, 3% were characterized as P. multocida subsp. septica, 5% as P. multocida. 5% as Pasteurella canis, and the remaining 5% represented a homogeneous group of unknown species belonging to the Pasteurellaceae.
There are multiple serotypes and strains of Pasteurella multocida. A capsule can be demonstrated in recently isolated cultures. The large polysaccharide capsule interferes with phagocytosis and protects against the adherence of complement proteins thus making natural elimination by the host animal more difficult. There are five capsule types: A, B, D, E, F and 16 somatic antigen determinants of lipopolysaccharide. The most common capsule type in the rabbit is type A, which is more adhesive to respiratory mucosa than other strains. Some strains also produce hyaluronidase and neuraminidase. These enzymes are thought to be significant predisposing
factors that allow infection to spread to adjacent tissues after inoculation of the respiratory system. Some Pasteurella multocida isolates also produces a heat-labile exotoxin (PMT) encoded by the toxA gene that enhances attachment to mucosal tissues and causes turbinate atrophy and atrophic rhinitis. Endotoxins are produced by all forms of P. multocida, both virulent and avirulent isolates. Endotoxins may contribute to virulence, but there needs to be enough growth and invasion of Pasteurella for the in vivo production of sufficient quantities of endotoxin to contribute to the pathologic process. An endotoxin produced by P. multocida can cause fever, inflammation, shock, while lowering bactericidal activity.
Pathogenesis of disease
Rabbits may be exposed to P. multocida through indirect contact, such as exposure to fomites, or via direct contact such as inhalation or direct inoculation of wounds. Pasteurellosis can also be transmitted vertically to kits or horizontally following copulation. After exposure to Pasteurella spp., the individual rabbit can resist infection, spontaneously clear the bacteria, become an asymptomatic carrier, or develop acute or chronic disease. Rhinitis may develop within 1-2 weeks following exposure to P. multocida. Anywhere from 40% to 72% of clinically normal rabbits harbor this organism; however, exposure to temperature fluctuations and poor sanitation can predispose rabbits to clinical disease.
The most common presentation of P. multocida infection is upper respiratory tract disease. Pasteurella multocida was identified as a cause of mucopurulent rhinitis in rabbits or “snuffles” in the 1920s. Clinical signs include mucopurulent nasal discharge, sneezing, congestion, and/or snoring. Infection of the nasolacrimal duct may extend to the conjunctiva causing ocular discharge and nasolacrimal duct obstruction. Affected rabbits may also have moisture or purulent material on their forelimbs following grooming. Bordetella bronchiseptica is a common inhabitant of the respiratory tract of rabbits; and concurrent overgrowth of B. bronchiseptica may enhance colonization of the nasal mucosa and sinuses with P. multocida.
If P. multocida infection descends to the lower respiratory tract, fibrinopurulent pneumonia, pleuritis, pericarditis, or solitary pulmonary abscesses can also be seen (Fig 1). Affected rabbits often present with anorexia, depression, weight loss, and dyspnea. Physical examination findings may include tachypnea, open-mouth breathing, cyanosis, rales and rattles, and/or reduced resonance on percussion of the thorax.
From the pharynx, bacterial infection can spread to the middle ear via the Eustachian tubes causing otitis media. Disease can then progress to otitis interna resulting in head tilt, nystagmus, and ataxia (Fig 2).
Pasturellosis may also be associated with abscesses in subcutaneous tissues, the retrobulbar space, the globe, or internal organs. These abscesses are well encapsulated, slowly enlarging masses that contain thick, white exudate that does not drain (Fig 3A, Fig 3B). Infection can also spread to the bones or joints causing dental abscesses, osteomyelitis, or septic arthritis. Finally, most pathogenic strains of P. multocida can spread systemically leading to non-specific signs of illness, fever, or sudden death. Post-mortem findings include congestion, petechiation, and microscopic abscesses throughout the viscera. Bacteremia can lead to pleuropneumonia, endocarditis, orchitis, or pyometra (Fig 4).
Although pasteurellosis remains a leading cause of respiratory disease in rabbits, it is important to remember that bacterial respiratory infections can also be caused by other microbes such as B. bronchiseptica, Staphylococcus spp., and Pseudomonas spp.
Diagnosis of pasteurellosis is based both on presentation and clinical signs as well as laboratory testing. Clinical pathology and imaging may also support a diagnosis of pasteurellosis. Complete blood count (CBC) findings in affected animals may show an inflammatory leukogram, but are often within normal limits. Serum chemistries are usually unremarkable. Radiography of rabbits with pneumonia reveals a bronchointerstitial or alveolar pattern in the lungs (Fig 5). In rabbits with otitis, skull radiographs may show increased density in the tympanic bullae. Decreased density may be seen within the nasal and sinus cavities in cases of atrophic rhinitis.
Cytologic samples may demonstrate many rod-shaped bacteria and degenerative heterophils. As with any bacterial infection, it is important to collect bacterial culture samples from suspect lesions prior to initiating antimicrobial therapy. Some rabbit owners may be reluctant to pursue diagnostics due to cost concerns and will opt for empirical antimicrobial therapy instead. Clients should be warned that Gram-negative bacteria, including Pasteurella spp., have unpredictable antibiotic susceptibilities.
Current laboratory methods used to diagnose pasteurellosis include culture, ELISA, and PCR testing. Culture techniques entail swabbing a sample onto culture media. Pasteurella multocida grows in most common laboratory media such as nutrient agar. Blood agar and CSY agar with 5% blood (bovine, sheep) are convenient media for routine laboratory culture. The optimum growth temperature is 35-37°C (95.0-98.6°F). In enriched media at 37°C, colonies 1-3 mm in diameter are produced after 18-24 hours culture. Colonies may range from relatively large, translucent, grayish in color, and mucoid in consistency to rounded, convex, discrete colonies with circular edges or large, watery colonies with flowing margins. Culture allows suspect colonies to be identified in 24-48 hours. Confirmation with biochemical diagnosis may take 72 hours or longer from the receipt of the culture swab. Unfortunately P. multocida can be difficult to culture due to competition from other organisms resulting in a false negative result.
PCR tests are fast (24 hours or less), very specific, and more sensitive than culture. PCR is used to detect DNA specific to P. multocida. The current use of this test requires an initial culture, PCR amplification, and the running of gel electrophoresis to identify the DNA of P. multocida.
A commercial serum ELISA may be used to detect antibodies to P. multocida. Serology is a reliable screening test for rabbit colonies; however, unless titers are significantly elevated, results may be equivocal in individual patients. High antibody levels correlate well with chronic infections but it takes 2-3 weeks for titers to rise substantially. Paired serology demonstrating a rising titer or a single positive serology plus positive culture are considered diagnostic.
Polymerase chain reaction testing (PCR) is used to detect DNA specific to P. multocida. The current use of this test requires an initial culture, PCR amplification, and the running of gel electrophoresis to identify the DNA of P. multocida.
Despite the seemingly wide variety of antibiotics to which Pasteurella spp. is susceptible, the risk of dysbiosis limits the oral use of most of these drugs. Most strains are reportedly sensitive to chloramphenicol, tetracyclines, and sulfonamides. Higher generation macrolides, such as azithromycin, have also been used with some success. Penicillin (40,000 IU/kg subcutaneously every 24 hours for 2 weeks then every 48 hours for 2 week) and enrofloxacin (5-10 mg/kg orally every 12 hours for 2-3 months) are also reportedly effective against chronic infections. Unfortunately, many owners do not comply with long-term regimens and will cease giving medication as soon as obvious symptoms subside, resulting in recrudescence of infection. McKay et al reported successful elimination of clinical signs in a colony of rabbits after only one to two doses of tilmicosin, but human health risks have prevented this antibiotic from being widely used in private practice.
Ophthalmic antibiotic drops, such as ciprofloxacin or gentamicin, can be used to treat conjunctivitis, dacryocystitis, or instilled into ear canals or nares for treatment of otitis or rhinitis respectively. Preparations containing glucocorticoids should be avoided as rabbits appear particularly sensitive to the adverse effects of steroids. Caution must be used with gentamicin as ingestion of the drops could cause dysbiosis. Nasolacrimal ducts can also safely be flushed with saline to relieve obstructions (Fig 6). Continue antibiotic treatment until clinical signs have resolved and serology is negative.
Medication alone is unlikely to be effective for treatment of abscesses. Abscesses can be drained and the capsule debrided, but if the entire capsule is not removed infection will recur. Therefore most abscesses must be surgically. excised. Abscesses that cannot be removed surgically should be left open to drain and cleaned daily.
Antibiotic impregnated polymethylmethacrylate (AIPMMA) beads can be implanted into abscess cavities before closure and are especially helpful with bone or dental abscesses, in which resection options are limited. Antibiotic-impregnated beads are widely used in human medicine, especially in cases of osteomyelitis, and are considered the gold standard for local delivery of antimicrobials in human orthopedic surgery. The use of AIPMMA beads allows delivery of a higher concentration of antibiotic to the local area than can be achieved systemically, and allows the medication to reach avascular areas that would otherwise be poorly penetrated by the medication. In addition, the use of antibiotics that would be toxic to use orally or impractical to use parenterally such as cefazolin or amikacin can be achieved using AIPMMA beads with little risk of systemic or enteral toxicity. In a study of antibiotic elution by Phillips et al it was found that the concentrations of cefazolin and amikacin were maintained above the MIC for 30 days when antimicrobials were used individually. Combining two antibiotics in the same bead was not recommended as this resulted in a shorter duration of action.
Once the infection is well controlled, the AIPMMA beads may be surgically removed. Difficulty with bead removal can occur when beads are left in place for longer than 3 weeks. However beads generally do not cause clinical problems when left in place, as they are biologically inert. Indications for bead removal include:
- The presence of a fistulous tract or new abscess formation around the beads
- Interference with normal function, such as when beads are placed within a joint.
- Bead placement within a mucosa-lined structure such as the nasal cavity as they may cause chronic discharge.
Beads may also need to be removed if they are placed in a location that creates pressure and subsequent sores such as on the bottom of the foot in the treatment of pododermatitis. If removal of the beads is planned, string the beads on an orthopedic wire or nonabsorbable suture. To remove the AIPMMA beads, the surgeon must locate one bead and the remainder can be removed by pulling the string.
Prevention and control
Maintaining good husbandry and hygiene, especially in breeding colonies, minimizes the risk of clinical disease. Provide adequate ventilation and minimize stress by avoiding sudden changes in the rabbit’s environment and prevent exposure to temperature extremes. Quarantine newly acquired rabbits prior to introduction into a household of established rabbits, and consider serology and/or culture to screen new rabbits for prior exposure to P. multocida.
Isolate sick rabbits that test positive for pasteurellosis, and prevent transmission via fomites. Disinfect surfaces with sodium hypochlorite or benzalkonium chloride. The antiseptic chlorhexidine is also effective against P. multocida.
If removed from sources of infection early, a rabbit may never acquire P.multocida infection. Pasteurella-free rabbit colonies are common in research settings. When rederiving colonies, kits are delivered by cesarean section then fostered onto clean does.
Vaccine strategies have been researched utilizing P. multocida vaccines containing inactivated PMT. As of yet, these vaccines have not been successful and there are currently no products commercially available.
Pasteurellosis is a widespread and common disease of pet rabbits, and the companion rabbit practitioner is likely to be presented with affected rabbits on a regular basis. Diagnosis can be based on clinical signs and serology, but positive culture results are preferred for a definitive diagnosis since infections with other organisms can cause similar clinical signs. Treatment with long term antibiotics such as oral enrofloxacin or parenteral penicillin until resolution of clinical signs and negative serology results can result in resolution of symptoms. Owners should be informed of the necessity of long-term treatment and good sanitation, as well as the risk that rabbits with apparent resolution of clinical signs may be possible carriers of the disease.