Pasteurella Multocida

Etiology

Pasteurella multocida most commonly causes soft tissue infection following a bite or scratch injury. While Pasteurella infection is most commonly associated with injury from domestic animals such as dogs and cats, the bacteria may also be transmitted through other animals such as rats, horses, rabbits, and more.[6] Penetrative injury is not always necessary for the transmission of the disease, as there have been cases of Pasteurella osteitis and meningitis after only being licked by a carrier animal.[7] Respiratory and other invasive infections (i.e., bacteremia, meningitis, endocarditis) are rare and occur almost exclusively in the immunocompromised, elderly, neonates, or in those with chronic pulmonary disease.[4][8]

Epidemiology

In the United States, approximately 300,000 patients are seen annually in emergency departments for animal scratches or bites.[6] Pasteurella multocida is the pathogen most commonly associated with infection in these patients.[1] Pasteurella species are part of the normal flora of the mouth and upper respiratory tract of many animals, both wild and domestic. The animals with the highest rate of carriage are cats, with rates of 70% to 90%. Dogs have the second-highest rate of carriage at 20% to 50%.[9] Consequently, one study found that Pasteurella species can be isolated in wound cultures in 50% of injuries from dog bites and 75% of injuries from cat bites.[10] Less commonly, Pasteurella infection may occur in the absence of physical injury. While rare, there have been cases of patients suffering from serious infections after only being licked by an animal.[7]

Respiratory infections are rare and almost exclusively occur in the immunocompromised or in those with chronic pulmonary disease.[8] This is also the case for invasive infections, such as meningitis and endocarditis. These usually occur in neonates, the elderly, or in immunocompromised.[4]

Pathophysiology

Pasteurella multocida is a gram-negative coccobacillus. It is a non-motile, facultative anaerobe and is generally penicillin-sensitive.[5] There are five commonly isolated serogroups (A, B, D, E, and F), which are classified by the composition of the polysaccharide capsule. Most human infections are caused by serogroups A and D. The bacterium has a variety of factors that contribute to its virulence, including a polysaccharide capsule which deters host immune-mediated destruction, a surface lipopolysaccharide molecule, iron acquisition proteins, and the Pasteurella multocida toxin.[6] The most common mode of infection of Pasteurella multocida is via an animal bite or scratch. This infection typically has a rapid course and develops within 24 hour hours of injury. It is characterized by erythematous swelling around the area of injury, tenderness, and often purulent drainage. Cellulitis may develop within one to two days.[8] 

In rare cases, necrotizing fasciitis may also occur, presenting with rapidly progressive infection and pain out of proportion to the physical exam.[11] In addition to soft tissue infection, osteomyelitis or septic arthritis may develop distal to the injury. These types of infections are more common in patients with comorbidities such as diabetes, alcoholism, or corticosteroid use, as well as in those with previously damaged joints via degenerative disease or joint replacement.[8] Interestingly, up to one-third of cases of septic arthritis caused by Pasteurella multocida are not preceded by a bite or scratch injury.[12] 

Respiratory disease caused by Pasteurella multocida follows a relatively nonspecific course, with cough fever, shortness of breath, and chest pain being common complaints. Pneumonia is the most common type of infection, although tracheobronchitis, empyema, and lung abscesses may also occur.[8] Other invasive infections, such as endocarditis, meningitis, and sepsis, do not have any defining features specific to the Pasteurella pathogen.

History and Physical

Patients with Pasteurella multocida infection will most commonly present following an injury due to an animal scratch or bite. The presentation may be immediately after the injury and before signs of infection have had time to develop. Infection may develop from 3 to 48 hours after the initial injury. Typical signs of Pasteurella infection include rapidly progressing swelling, erythema, and tenderness around the injury site. Serosanginous or purulent drainage may be present, as well as local lymphadenopathy.[8] In rare cases, the infection may progress to necrotizing fasciitis. In these cases of unusually rapid spread, patients may present with pain out of proportion to the physical exam and crepitus of the affected tissue. Some soft tissue infections may lead to bacteremia, which often manifests as fever, tachycardia, and hypotension.

In addition to soft tissue infection, septic arthritis and osteomyelitis are also possible sequelae of Pasteurella infection. Septic joints are not typically a result of direct inoculation and are located distal to the site of initial skin penetration. Patients that are more likely to suffer from a septic joint are those with comorbidities such as diabetes, alcoholism, or chronic corticosteroid use. A previous history of joint damage due to joint replacement or chronic degenerative disease also puts patients at a higher risk for septic arthritis. The most common joint affected is the knee.

One-third of patients suffering from septic arthritis secondary to Pasteurella multocida infection will not report a history of injury due to a bite or scratch, so it is important to obtain a detailed history of possible animal exposure. Patients that suffer from deep, penetrating wounds (typically cat bites) may also develop osteomyelitis. Wounds that penetrate the periosteum are more likely to lead to osteomyelitis, but direct inoculation is unnecessary. Localized extension of a soft tissue infection may eventually involve the bone itself. There is a particularly high risk of combined osteomyelitis and septic arthritis in patients suffering from cat bites to the hand.[5]

Respiratory or invasive infections (i.e., endocarditis, meningitis) caused by Pasteurella multocida are not characterized by any specific features which might aid in definitive diagnosis. A thorough history that reveals animal exposure in the context of an immunocompromised state or other risk factors may raise suspicion for Pasteurella infection in these patients.

Evaluation

Patients presenting with an animal bite or scratch should receive an X-ray of the affected area to evaluate for any fractures, retained foreign body, signs of osteomyelitis, or signs of necrotizing infection. A complete blood count (CBC) can be ordered to look for evidence of immune response to infection. Erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) may also be ordered to assess for inflammatory response and osteomyelitis risk. Wound cultures can be collected to identify local infection and blood cultures if there is a concern for systemic infection. In cases of suspected osteomyelitis, a magnetic resonance imaging scan (MRI) can be ordered to further evaluate. If septic arthritis is a concern, arthrocentesis should be performed for confirmation. For those presenting with respiratory complaints, a sputum culture may aid in a definitive diagnosis. Patients presenting with symptoms of meningitis should undergo lumbar puncture, and a cerebrospinal fluid (CSF) culture should be sent to determine the ultimate pathogen.

The recommended medium on which to grow Pasteurella multocida is 5% sheep's blood agar at 37 degrees celsius. The bacteria are gram-negative, non-motile coccobacilli that are facultative anaerobes. Most strains are penicillin-sensitive and test positive for catalase, oxidase, indole, sucrose, and decarboxylate ornithine.[6]

Treatment / Management

Management of Uncomplicated Animal Bite/Scratch

As with any traumatic injury, the patient's airway, breathing, and circulation must be evaluated and secured before moving on to treating the injury. Once the patient is hemodynamically stable, the wound should be flushed with copious amounts of sterile water (under local anesthesia if necessary). An x-ray of the affected area should be obtained to evaluate for underlying fracture or retained foreign body. Primary closure of the wound should be done only if necessary, as this increases the risk of developing an infection. If closure is performed, space should be left between sutures to allow for drainage. Tetanus prophylaxis should be given if indicated. Consider rabies prophylaxis for all animal-related injuries. 

Prophylactic antibiotics are not currently recommended universally for animal bites or scratches. High-risk patients include those that are immunosuppressed or immunocompromised (i.e., patients with diabetes mellitus, asplenia, or cirrhosis) as well as patients with degenerative joint disease or prosthetic joint replacements. Injuries that are classified as high-risk include any injury to the hand, injuries to the face or genitals, any injury that requires surgical repair or primary closure, deep puncture wounds or lacerations (more common in cat bites), wounds with associated crush injury (more common in dog bites), and wounds that are close to the bone or joint (especially prosthetic joints).[13][14][15](A1)

Barring any complications associated with their injuries, these patients are generally safe for discharge home with close follow-up. If antibiotic prophylaxis is given, an oral treatment for 3 to 5 days is sufficient. Specific regimens are discussed below. The patient should be advised to seek re-evaluation for any sign of developing an infection.

Management of Complicated Infected Injury

Complications of infected injury include systemic illness (fever, hypotension, tachycardia) and spread to deeper soft tissues. Rapid progression of symptoms may also occur despite oral antibiotic therapy. Parenteral antibiotics should be considered in these patients, as well as in those previously identified as high-risk. If parenteral antibiotics are used, they should be continued until the patient shows clear signs of resolving infection, at which point the transition to an oral regimen for an additional 5-14 days is suggested.

Surgical management may be indicated for deeper soft tissue infections, including wounds with devitalized tissue, evidence of abscess formation, or developing characteristics of necrotizing infection. If debridement is necessary, it should be performed before the initiation of antibiotics so that wound samples can be sent for culture. If possible, wound closure should be avoided following debridement to allow for adequate drainage. In patients that require superficial wound debridement or abscess drainage without other signs of systemic infection, discharge with 5-14 days of oral antibiotics is a reasonable treatment option. The length of the regimen can be extended if the patient shows a slow response. Patients with complicated deep infections, such as osteomyelitis, tenosynovitis, or septic arthritis, may require a prolonged course of antibiotics. Specific regimens are discussed below.[16](B3)

Management of Other Pasteurella Infection

There are no changes in the management of respiratory or systemic Pasteurella infection (such as pneumonia, meningitis, endocarditis, bacteremia, etc.) that are specific to the Pasteurella pathogen. These patients should be managed in a manner appropriate to their specific disease process.

Antibiotic Therapy or Prophylaxis

The first-line antibiotic for prophylaxis or active local infection is oral amoxicillin-clavulanate. Alternative therapy may include any combination of an antibiotic with anti-Pasteurella activity (such as doxycycline, trimethoprim/sulfamethoxazole, penicillin V, cefuroxime, ciprofloxacin, or levofloxacin) as well as an anti-anaerobic agent (such as metronidazole or clindamycin) to cover other oral flora.

First-line parenteral antibiotic treatment includes monotherapy with ampicillin-sulbactam, piperacillin-tazobactam, or a carbapenem (imipenem-cilastatin, meropenem, ertapenem). Ceftriaxone or a fluoroquinolone plus an anti-anaerobic agent (such as metronidazole or clindamycin) is also acceptable.

Antibiotic regimens should always be targeted based on cultures and sensitivities when appropriate.

Antibiotics that have been shown to have inadequate anti-Pasteurella activity (including cephalexin, dicloxacillin, and erythromycin) should be avoided.[15](A1)

Differential Diagnosis

While Pasteurella multocida is the most common pathogen isolated from animal bites or scratches, these other pathogens should also be considered:

• Bartonella henselae
• Clostridium tetani
• Staphylococcus aureus
• Rabies lyssavirus

Prognosis

Soft-tissue infections associated with Pasteurella multocida generally have an uncomplicated course and resolve with appropriate treatment. Infections in the hand, however, have a worse prognosis due to high rates of complication. Possible complications that may lead to long-term morbidity include tenosynovitis, osteomyelitis, and septic arthritis.[2] 

In more serious presentations such as bacteremia, meningitis, and endocarditis, the prognosis is significantly worse. Mortality is 25% to 30% in these conditions.[6]

Complications

If prompt treatment is not initiated for an infected animal bite, complications may occur. In the worst cases, systemic illness (bacteremia, endocarditis, meningitis) may develop. Local complications include abscess formation, septic arthritis, osteomyelitis, and tenosynovitis. These local complications occur most commonly in injuries to the hand.