Pasteurellosis in Rabbits: Pasteurella multocida Respiratory Infections and Treatment

Introduction

Pasteurellosis, caused by the Gram-negative coccobacillus Pasteurella multocida, is the most prevalent bacterial disease of domestic rabbits (Oryctolagus cuniculus). The pathogen is a primary component of the rabbit upper respiratory tract microbiota but can transition to an opportunistic invasive pathogen under conditions of stress, immunosuppression, or concurrent viral infection [1, 2]. The clinical spectrum ranges from subclinical nasal carriage to severe suppurative rhinitis, pneumonia, otitis media, conjunctivitis, and abscess formation in subcutaneous and visceral sites [3, 4]. This article provides a detailed review of the pathogenesis, clinical presentation, diagnostic methods including culture and serotyping, antimicrobial susceptibility patterns, and medical and surgical treatment strategies for P. multocida infections in rabbits.

Etiology and Pathogenesis

Pasteurella multocida is a facultative anaerobic, non-motile, encapsulated bacterium belonging to the family Pasteurellaceae. The organism expresses a polysaccharide capsule that is a major virulence factor, with five capsular serogroups (A, B, D, E, F) identified in various animal hosts [5]. In rabbits, capsular serogroup A and, less frequently, serogroup D are the predominant isolates associated with clinical disease [6, 7]. Lipopolysaccharide (LPS) and outer membrane proteins (OMPs) contribute to the inflammatory response and resistance to phagocytosis [8].

The pathogenesis of pasteurellosis begins with colonization of the nasal mucosa. P. multocida adheres to ciliated epithelial cells via fimbriae and other adhesins, leading to ciliostasis and disruption of mucociliary clearance [9]. Bacterial proliferation triggers a neutrophilic inflammatory response, resulting in mucopurulent exudate. From the nasal cavity, the organism can ascend the Eustachian tube to cause otitis media, descend into the lower respiratory tract to cause bronchopneumonia, or enter the bloodstream to seed distant sites such as the mammary glands, uterus, and subcutaneous tissues [10, 11]. Abscess formation is a hallmark of chronic infection; the thick, caseous pus is surrounded by a fibrous capsule that limits antibiotic penetration and immune cell access [12].

Clinical Signs

Rhinitis and Sinusitis

The most common manifestation of pasteurellosis is chronic rhinitis, often termed "snuffles." Affected rabbits exhibit serous to mucopurulent nasal discharge, sneezing, and pawing at the nares [13]. The discharge may become crusted around the nostrils, and secondary conjunctivitis with epiphora is frequently observed. In chronic cases, the nasal turbinates may become eroded, leading to persistent infection and intermittent dyspnea [14].

Abscess Formation

Subcutaneous abscesses are a frequent sequela of disseminated infection. These abscesses are typically firm, non-painful, and slow-growing. They can occur on the face, limbs, trunk, or perineum. The purulent material is thick, caseous, and often described as "toothpaste-like" due to the high fibrin and cellular debris content [15]. Abscesses may also develop in deeper structures, including the retrobulbar space, causing exophthalmos, and the mammary glands, causing mastitis [16].

Otitis Media and Interna

Ascending infection from the nasopharynx via the Eustachian tube is the primary route for otitis media. Clinical signs include head tilt (torticollis), nystagmus, circling, and ataxia [17]. The condition can progress to otitis interna with vestibular syndrome. In some cases, the tympanic bulla becomes filled with purulent exudate, and the infection may extend to the meninges, causing meningitis [18].

Pneumonia

Lower respiratory tract infection is less common but carries a high mortality rate. Rabbits with pneumonia present with tachypnea, dyspnea, cyanosis, and fever. Auscultation may reveal crackles and wheezes. The disease can progress rapidly to septic shock and death [19].

Other Manifestations

P. multocida can cause conjunctivitis, genital tract infections (metritis, orchitis), and septicemia in neonates [20]. In breeding does, mastitis and abortion have been reported [21].

Diagnostic Approaches

Culture and Isolation

Definitive diagnosis relies on isolation of P. multocida from clinical specimens. Samples are collected via deep nasal swabs, aspiration of abscess contents, or swabs of the tympanic bulla during surgery. The organism grows readily on blood agar or chocolate agar under aerobic conditions with 5% carbon dioxide at 35-37 degrees Celsius for 24-48 hours [22]. Colonies are small, gray, and non-hemolytic. A characteristic "mousy" odor is often noted. Gram staining reveals Gram-negative coccobacilli. Biochemical identification can be performed using commercial identification systems or by detecting oxidase and catalase positivity, indole production, and lack of hemolysis on sheep blood agar [23].

Serotyping

Serotyping is performed using the Heddleston scheme, which identifies 16 somatic serotypes (1-16) based on heat-stable LPS antigens [24]. In rabbits, serotypes 3, 4, and 12 are most commonly associated with disease [25]. Capsular typing via multiplex PCR targeting the capsular biosynthesis genes (hyaD-hyaC for serogroup A, bcbD for serogroup D) is increasingly used for epidemiological studies [26].

Molecular Diagnostics

PCR assays targeting the P. multocida-specific gene kmt1 or the 16S rRNA gene provide rapid and sensitive detection directly from clinical samples [27]. Real-time PCR can quantify bacterial load and is useful for monitoring treatment response. Multiplex PCR panels that differentiate P. multocida from other respiratory pathogens such as Bordetella bronchiseptica and Staphylococcus aureus are available [28].

Antimicrobial Susceptibility Testing

Given the emergence of antimicrobial resistance, disk diffusion or broth microdilution testing should be performed on all isolates [29]. The Clinical and Laboratory Standards Institute (CLSI) guidelines for veterinary pathogens are used for interpretation. Common antibiotics tested include fluoroquinolones, tetracyclines, penicillins, cephalosporins, and sulfonamides [30].

Treatment Strategies

Medical Therapy

Antibiotic selection is guided by culture and sensitivity results. The following table summarizes commonly used antibiotics for pasteurellosis in rabbits.

Fluoroquinolones such as enrofloxacin and marbofloxacin are first-line agents due to their excellent bioavailability, tissue penetration, and activity against P. multocida [38]. Doxycycline is a common alternative for chronic rhinitis because of its anti-inflammatory properties and ability to concentrate in respiratory secretions [39]. Penicillins are effective but carry a risk of inducing fatal enterotoxemia from Clostridium overgrowth in the cecum; they should be used only when no alternative exists and with concurrent probiotic administration [40].

Duration of therapy is typically 2-4 weeks for rhinitis and 4-8 weeks for abscesses and otitis media. Relapses are common, and long-term suppressive therapy may be required in chronic cases [41].

Surgical Management of Abscesses

Medical therapy alone is rarely curative for abscesses due to the thick fibrous capsule and caseous core. Surgical drainage is the cornerstone of treatment. The approach involves:

1. Lancing and debridement: The abscess is incised, and all purulent material is removed. The capsule should be excised if possible, as it is avascular and prevents antibiotic penetration [42].

2. Curettage and flushing: The cavity is curetted to remove necrotic tissue and then flushed copiously with sterile saline or 0.1% povidone-iodine solution. Hydrogen peroxide should be avoided as it damages healthy tissue [43].

3. Marsupialization: For large or recurrent abscesses, the capsule is sutured to the skin to create a permanent drainage tract. This allows ongoing drainage and topical treatment [44].

4. Antibiotic-impregnated beads: Polymethylmethacrylate (PMMA) beads loaded with gentamicin or clindamycin can be placed in the cavity to provide sustained local antibiotic concentrations [45].

5. Systemic antibiotics: A 4-6 week course of antibiotics based on culture results is administered postoperatively [46].

Treatment of Otitis Media

Otitis media requires a combination of medical and surgical therapy. Systemic antibiotics are given for 6-8 weeks. If there is no improvement, a bulla osteotomy is performed to drain the tympanic cavity and remove infected material [47]. The approach can be ventral or lateral; the ventral approach is preferred for bilateral disease as it allows access to both bullae [48].

Prognosis and Prevention

The prognosis for rhinitis is fair to good with appropriate therapy, but relapses are common. Abscesses have a guarded prognosis, especially if they involve bone or vital structures. Otitis media with neurologic signs carries a poor prognosis if treatment is delayed [49].

Prevention focuses on reducing stress, maintaining good ventilation and hygiene, and avoiding overcrowding. Routine screening of breeding stock by nasal culture or PCR can identify carriers. Vaccines are available for poultry and swine but are not licensed for rabbits; autogenous vaccines have been used experimentally with variable success [50].

Conclusion

Pasteurella multocida remains the most significant bacterial pathogen of domestic rabbits, causing a spectrum of respiratory and systemic diseases. Successful management requires accurate diagnosis through culture and molecular methods, targeted antibiotic therapy based on susceptibility testing, and aggressive surgical intervention for abscesses and otitis media. A thorough understanding of the pathogenesis and clinical presentation is essential for effective treatment and control.

References

[1] Deeb BJ, DiGiacomo RF. Respiratory diseases of rabbits. Vet Clin North Am Exot Anim Pract. 2000;3(2):465-480.

[2] Manning PJ, DiGiacomo RF, DeLong D. Pasteurellosis in laboratory rabbits. Lab Anim Sci. 1989;39(5):405-410.

[3] Flatt RE, Deyo BL. Pasteurella multocida infection in rabbits. J Am Vet Med Assoc. 1974;165(7):630-632.

[4] Percy DH, Barthold SW. Pathology of Laboratory Rodents and Rabbits. 3rd ed. Blackwell Publishing; 2007.

[5] Carter GR. Pasteurellosis: Pasteurella multocida and Pasteurella haemolytica. Adv Vet Sci. 1967;11:321-379.

[6] Lu YS, Pakes SP. Identification of capsular serotypes of Pasteurella multocida from rabbits. J Clin Microbiol. 1981;14(5):503-506.

[7] Jaglic Z, Jeklova E, Leva L, et al. Experimental study of pathogenicity of Pasteurella multocida serogroup A in rabbits. Vet Microbiol. 2008;126(1-3):168-177.

[8] Harper M, Boyce JD, Adler B. Pasteurella multocida pathogenesis: 125 years after Pasteur. FEMS Microbiol Lett. 2006;265(1):1-10.

[9] Glorioso JC, Jones GW, Rush HG, et al. Adhesion of Pasteurella multocida to rabbit pharyngeal cells and its possible role in the pathogenesis of atrophic rhinitis. Infect Immun. 1982;35(3):1103-1109.

[10] DiGiacomo RF, Garlinghouse LE, Van Hoosier GL. Natural history of infection with Pasteurella multocida in rabbits. J Am Vet Med Assoc. 1983;183(11):1172-1175.

[11] Okerman L. Diseases of Domestic Rabbits. 2nd ed. Blackwell Science; 1994.

[12] Brown SA. Surgical management of abscesses in rabbits. Vet Clin North Am Exot Anim Pract. 2006;9(3):581-596.

[13] Harkness JE, Wagner JE. The Biology and Medicine of Rabbits and Rodents. 4th ed. Williams and Wilkins; 1995.

[14] Rougier S, Galland D, Boucher S, et al. Epidemiology and susceptibility of pathogenic bacteria responsible for upper respiratory tract infections in pet rabbits. Vet Microbiol. 2006;115(1-3):192-198.

[15] Harcourt-Brown F. Textbook of Rabbit Medicine. Butterworth-Heinemann; 2002.

[16] Varga M. Textbook of Rabbit Medicine. 2nd ed. Elsevier; 2014.

[17] Krogstad O, Hagen G. Otitis media in rabbits: clinical and pathological findings. J Small Anim Pract. 1992;33(6):277-282.

[18] Snyder SB, Fox JG, Soave OA. Pasteurella multocida infection in rabbits: a review. Lab Anim Sci. 1973;23(3):394-398.

[19] Johnson-Delaney CA. Rabbit respiratory disease: a review. J Exot Pet Med. 2007;16(3):156-163.

[20] DiGiacomo RF, Jones CD, Wathes CM. Transmission of Pasteurella multocida in rabbits. Lab Anim Sci. 1987;37(5):621-624.

[21] Saito K, Nakayama M, Sasaki T, et al. Mastitis caused by Pasteurella multocida in rabbits. J Vet Med Sci. 2001;63(7):799-801.

[22] Quinn PJ, Carter ME, Markey BK, et al. Clinical Veterinary Microbiology. Mosby; 1994.

[23] Markey BK, Leonard FC, Archambault M, et al. Clinical Veterinary Microbiology. 2nd ed. Mosby Elsevier; 2013.

[24] Heddleston KL, Gallagher JE, Rebers PA. Fowl cholera: gel diffusion precipitin test for serotyping Pasteurella multocida from avian species. Avian Dis. 1972;16(4):925-936.

[25] Brogden KA, Rhoades KR, Heddleston KL. A new serotype of Pasteurella multocida associated with fowl cholera. Avian Dis. 1978;22(1):185-190.

[26] Townsend KM, Boyce JD, Chung JY, et al. Genetic organization of Pasteurella multocida cap loci and development of a multiplex capsular PCR typing system. J Clin Microbiol. 2001;39(3):924-929.

[27] Miflin JK, Blackall PJ. Development of a 23S rRNA-based PCR assay for the identification of Pasteurella multocida. Lett Appl Microbiol. 2001;33(3):216-221.

[28] Register KB, DeJong KD. Analytical validation of a real-time PCR assay for detection of Pasteurella multocida. J Vet Diagn Invest. 2006;18(4):369-374.

[29] Watts JL, Sweeney MT. Antimicrobial susceptibility testing of veterinary pathogens. Vet Clin North Am Food Anim Pract. 2010;26(1):1-14.

[30] Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated from Animals. 5th ed. CLSI; 2020.

[31] Carpenter JW, Mashima TY, Rupiper DJ. Exotic Animal Formulary. 3rd ed. Elsevier; 2005.

[32] Plumb DC. Plumb's Veterinary Drug Handbook. 9th ed. Wiley-Blackwell; 2018.

[33] Morrissey I, Smith R, Biedenbach D, et al. Activity of doxycycline against respiratory pathogens. Int J Antimicrob Agents. 2005;25(6):487-492.

[34] Baggot JD. The Physiological Basis of Veterinary Clinical Pharmacology. Blackwell Science; 2001.

[35] Katz L, Lamport AI, Smit JA. Effects of penicillin on the rabbit cecal flora. Lab Anim Sci. 1978;28(4):423-427.

[36] Salmon SA, Watts JL. In vitro activity of ceftiofur against Pasteurella multocida. J Vet Pharmacol Ther. 1996;19(5):395-397.

[37] Prescott JF, Baggot JD, Walker RD. Antimicrobial Therapy in Veterinary Medicine. 3rd ed. Iowa State University Press; 2000.

[38] Boothe DM. Small Animal Clinical Pharmacology and Therapeutics. 2nd ed. Elsevier; 2012.

[39] Giguere S, Prescott JF, Dowling PM. Antimicrobial Therapy in Veterinary Medicine. 5th ed. Wiley-Blackwell; 2013.

[40] Fekete S, Bokori J. The effect of antibiotic therapy on the intestinal microflora of rabbits. J Appl Rabbit Res. 1985;8(3):115-118.

[41] Paul-Murphy J. Critical care of the rabbit. Vet Clin North Am Exot Anim Pract. 2007;10(2):437-461.

[42] Bennett RA. Soft tissue surgery in rabbits. J Exot Pet Med. 2007;16(4):231-240.

[43] Lennox AM. Management of abscesses in rabbits. Vet Clin North Am Exot Anim Pract. 2006;9(3):597-610.

[44] Harcourt-Brown F. Abscesses in rabbits. In: Proceedings of the British Small Animal Veterinary Association Congress; 2001:345-346.

[45] Ethell MT, Bennett RA, Brown MP, et al. In vitro elution of gentamicin from polymethylmethacrylate beads in rabbits. Vet Surg. 2000;29(5):468-473.

[46] Jenkins JR. Soft tissue surgery in rabbits. In: Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. 3rd ed. Elsevier; 2012:267-278.

[47] Chow EP, Bennett RA, Della Ratta M. Ventral bulla osteotomy for treatment of otitis media in rabbits. J Am Vet Med Assoc. 1993;202(10):1665-1668.

[48] King AM, Weinstein NM, Bennett RA. Surgical treatment of otitis media in rabbits. Vet Surg. 2004;33(5):511-516.

[49] Deeb BJ. Respiratory disease and pasteurellosis. In: Quesenberry KE, Carpenter JW, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. 3rd ed. Elsevier; 2012:205-213.

[50] Glisson JR, Hofacre CL, Christensen JP. Fowl cholera. In: Saif YM, ed. Diseases of Poultry. 12th ed. Blackwell Publishing; 2008:739-758.