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MICROBIOLOGY LEGEND CYCLE 40 ORGANISM 3 Pasteurella multocida

Pasteurella multocida (P. multocida) is a small, gram-negative, nonmotile, non–spore-forming coccobacillus with bipolar staining features. The bacteria typically appear as single bacilli on Gram stain; however, pairs and short chains can also be seen. P multocida often exists as a commensal in the upper respiratory tracts of many livestock, poultry, and domestic pet species, especially cats and dogs. In fact, Pasteurella species are some of the most prevalent commensal bacteria present in domestic and wild animals worldwide. P multocida infection in humans is often associated with an animal bite, scratch, or lick, but infection without epidemiologic evidence of animal contact may occur.

Pasteurella multocida infection. Wound infections associated with animal bites usually have a polymicrobial etiology, mandating the empiric use of broad-spectrum antimicrobials targeted at both aerobic and anaerobic gram-negative bacteria. Nevertheless, Pasteurella species are commonly isolated pathogens in most animal bites, especially in dog and cat related injuries. These injuries can be aggressive, with skin manifestations typically appearing within 24 hours following a bite. These wounds can exhibit a rapidly progressive soft-tissue inflammation that may resemble group A β- hemolytic Streptococcus pyogenes infections. Deeper soft tissue can also be affected, manifesting as tenosynovitis, septic arthritis, and osteomyelitis. More-severe disseminating infections may also develop, including endocarditis or meningitis, the latter mimicking Haemophilus influenzae or Neisseria meningitides infections in young children. Fortunately, Pasteurella species are fairly sensitive organisms and can be treated with a penicillin-based regimen.

Pathophysiology  Local: P multocida infection usually presents as an infection that complicates an animal bite or injury. Complications include rapidly progressive cellulitis, abscesses, tenosynovitis, osteomyelitis, and septic arthritis. The latter two are particularly common following cat bites because of their small, sharp, penetrative teeth.  Respiratory: P multocida may cause upper respiratory tract infections, including sinusitis, otitis media, mastoiditis, epiglottitis, pharyngitis and Ludwig angina. In rare cases, P multocida may also cause lower respiratory tract infections, including pneumonia, tracheobronchitis, lung abscess and empyema, usually in individuals with underlying pulmonary disease.  Cardiovascular: P multocida has been reported to cause native-and prosthetic-valve endocarditis, pericarditis, mycotic aneurysms, vascular graft infections, central venous catheter infections, bacteremia, sepsis, septic shock, and disseminated intravascular coagulation.  Central nervous system: P multocida is an uncommon cause of meningitis, subdural empyema, and brain abscess. P multocida meningitis has been associated with cat licks and bites occurring on the face in persons at the extremes of age.

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P.O. Box 131375, Bryanston, 2074 Ground Floor, Block 5 Bryanston Gate, 170 Curzon Road Bryanston, Johannesburg, South Africa www.thistle.co.za Tel: +27 (011) 463 3260 Fax: +27 (011) 463 3036 Fax to Email: + 27 (0) 86-538-4484 e-mail : [email protected]  Gastrointestinal: P multocida rarely causes gastrointestinal problems but has been associated with appendicitis, hepatosplenic abscesses, and spontaneous bacterial peritonitis. P multocida has been isolated in patients with polymicrobial peritoneal dialysis catheter–associated peritonitis.  Ocular: P multocida periocular abscess, conjunctivitis, corneal ulcers, and endophthalmitis have been reported.  Genitourinary tract: P multocida pyelonephritis, renal abscess, epididymitis, and cervicitis have been reported in rare cases.

Mortality/Morbidity It is estimated that 10-20 human deaths per year occur following an animal bite. Infectious complications occur in approximately 15-20% of dog-related bites and more than 50% of cat-related ones. Following a bite, a rapidly progressive cellulitis may develop; deeper structures, including tendons, joints, and bones, can become affected, especially in cat-related injuries. Dissemination can occur. Degenerative joint disease, rheumatoid arthritis, and prosthetic joints have been associated with the development of P multocida septic arthritis. Chronic obstructive pulmonary disease is a risk factor for P multocida respiratory tract infection, which carries a mortality rate of approximately 30%. Diabetes mellitus and liver dysfunction are predisposing conditions associated with pasteurellosis and associated bacteremia. P multocida infections during pregnancy and in utero transmission have also been reported. Localized P multocida infections carry an excellent prognosis. Significant morbidity has been associated with musculoskeletal P multocida infections, especially those involving the hand. Disseminated P multocida infections carry a 25-30% overall mortality risk.

Age All age groups can be affected by P multocida infections. Young children seem to be frequently involved in nonfatal dog bites. P multocida meningitis typically occurs in persons at the extremes of age.

History A history of animal exposure, whether occupational or recreational, should alert the physician to the possibility of a zoonosis. A detailed pet history, including exposure to pets owned by friends or strangers, should reveal the possibility of Pasteurella infection. However, cases of Pasteurella infection occur in the total absence of an epidemiological link.

Causes Causes of P multocida infection include the following:  Dog bite or lick  Cat bite, lick, or scratch  Idiopathic (no history of pet exposure)  Immunosuppression

Laboratory Studies Gram stain of purulent material or other fluid specimens including blood, sputum, and cerebrospinal fluid may show small, gram-negative, nonmotile, non–spore-forming pleomorphic coccobacilli. Haemophilus species, N meningitides, Moraxella species, and Acinetobacter species have a morphology that is similar to that of P multocida infection and can therefore be easily confused with Pasteurella species. Wright, Giemsa, and Wayson stains enhance bipolar staining. Some P multocida strains exhibit a mucous capsule. Pasteurella species are highly sensitive to several penicillins and cephalosporins. Susceptibility testing is indicated in immunocompromised patients and in the setting of treatment failure or drug allergies.

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P.O. Box 131375, Bryanston, 2074 Ground Floor, Block 5 Bryanston Gate, 170 Curzon Road Bryanston, Johannesburg, South Africa www.thistle.co.za Tel: +27 (011) 463 3260 Fax: +27 (011) 463 3036 Fax to Email: + 27 (0) 86-538-4484 e-mail : [email protected]

Culture growing Pasteurella multocida Pasteurella multocida shown with Gram stain of culture growth

Treatment Antimicrobial resistance among Pasteurella isolates is rarely reported in humans. Tetracyclines, erythromycin, and penicillin are most commonly associated with resistance. Penicillin-resistant strains have been isolated only from respiratory tract infections. Most animal-bite injuries can be treated with oral antimicrobials on an outpatient basis. Severe or partially responding infections may necessitate hospitalization and parenteral antimicrobial administration, along with surgical intervention. Most Pasteurella isolates are susceptible to oral antimicrobials such as amoxicillin, amoxicillin/clavulanic acid, minocycline, fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin), and trimethoprim-sulfamethoxazole. Based on in vitro susceptibility data, several antimicrobials should not be used empirically for P multocida infections, including dicloxacillin, vancomycin, cephalexin, cefaclor, cefadroxil, erythromycin, and clindamycin. Macrolide resistance is usually encountered with erythromycin. Other macrolides, including azithromycin, clarithromycin, and telithromycin (in order of decreasing susceptibility), retain in vitro activity against most Pasteurella strains. Aminoglycosides have poor activity against P multocida.

More-severe infections may require parenteral antibiotics. Intravenous ampicillin-sulbactam, ticarcillin- clavulanate, piperacillin-tazobactam, cefoxitin, and carbapenems (imipenem-cilastatin, meropenem & ertapenem) are excellent empiric options for animal-bite injuries, providing gram-positive, gram-negative, and anaerobic coverage. The new tetracycline-derivative tigecycline also has excellent in vitro activity against P multocida and other pathogens encountered in animal and bite injuries. If P multocida is the only isolated organism, therapy may be changed to intravenous penicillin G. Once clinical improvement is noted, oral penicillin VK is an option. Patients with penicillin allergies can receive minocycline, doxycycline, fluoroquinolones, trimethoprim-sulfamethoxazole, or azithromycin.

Prognosis Soft-tissue P multocida infections carry an excellent prognosis. Deeper wounds, especially hand infections, may be associated with prolonged morbidity. P multocida pulmonary infections, CNS involvement, bacteremia, and endocarditis carry a mortality rate of approximately 30%.

References 1. http://emedicine.medscape.com/article/224920 2. http://www.idimages.org/images/organismdetail/?imageid=1726&altimageid=122

Questions 1. Discuss the morphological characteristics of P. multocida. 2. Discuss the lab findings of P. multocida. 3. Discuss the pathophysiology of P. multocida.

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