Pasteurella Multocida Infection


Background

Pasteurella 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. [1P multocida infection in humans is often associated with an animal bite, scratch, or lick, but infection without epidemiologic evidence of animal contact may occur. See the image below.


Pasteurella multocida infection. 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 tenosynovitisseptic 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.

Patients with P multocida infection who present without evidence of an animal bite are more likely to have invasive infection such as respiratory or bloodstream infection. [2]

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. [3The latter two are particularly common following cat bites because of their small, sharp, penetrative teeth. [4Non-native septic arthritis can also occur. [5]

Respiratory: P multocida may cause upper respiratory tract infections, including sinusitis, otitis media, mastoiditis, epiglottitis, [6pharyngitis, and Ludwig angina. [7In rare cases, P multocida may also cause lower respiratory tract infections, including pneumonia, tracheobronchitis, lung abscess, [8and empyema, [9usually in individuals with underlying pulmonary disease.

Cardiovascular: P multocida has been reported to cause native- [10and prosthetic-valve endocarditis, [11pericarditis, mycotic aneurysms, [12vascular graft infections, [13central venous catheter infections, bacteremia, sepsisseptic shock, [14and disseminated intravascular coagulation. [15]

Central nervous system: P multocida is an uncommon cause of meningitis, [16subdural empyema, and brain abscess. [17P multocida meningitis has been associated with cat licks and bites occurring on the face in persons at the extremes of age. [18]

Gastrointestinal: P multocida rarely causes gastrointestinal problems but has been associated with appendicitis, hepatosplenic abscesses, and spontaneous bacterial peritonitisP multocida has been isolated in patients with polymicrobial peritoneal dialysis catheter–associated peritonitis. [19]

Ocular: P multocida periocular abscess, [20conjunctivitis, corneal ulcers, and endophthalmitis have been reported.

Genitourinary tract: P multocida pyelonephritis, renal abscess, epididymitis, and cervicitis have been reported in rare cases.

Epidemiology

Frequency

United States

According to the American Pet Products Association, approximately 180 million dogs and cats live in the United States, cats currently outnumbering dogs by 12 million. Animal bites account for 1% (300,000) of annual emergency department visits. The estimated cost in health care expenditures has been reported to be $30 million per year. Approximately 10% of animal bites require medical attention; 1-2% eventually require hospitalization.

Approximately 5 million animal bites are reported annually. The vast majority of animal bites involve dogs (85-90%), followed by cats (5-10%).

Infectious complications occur in approximately 15-20% of dog-related bites and more than 50% of cat-related ones. Dog bites are associated with younger animals engaging in playful activities, mostly with children. German shepherd, pit bull, Staffordshire terrier, and mixed breeds are most commonly involved with human bites, while the golden retriever and Labrador retriever are least. Cat bites are usually provoked, typically by female felines, and occurring on the upper extremities or face. Sharp and long teeth of cats can easily penetrate human skin and create a deep puncture wound and even inoculate the periosteum component of bones. Indeed, cat-related wounds more commonly progress to more serious and deeper-tissue infections, including osteomyelitis and meningitis.

International

P multocida infections occur worldwide. Cats are involved in 60-80% of human P multocida infections. Moreover, P multocida is isolated in 50% of dog bites.

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. [21]

Chronic obstructive pulmonary disease is a risk factor for P multocida respiratory tract infection, [22which carries a mortality rate of approximately 30%. Diabetes mellitus [23and liver dysfunction [24are predisposing conditions associated with pasteurellosis and associated bacteremia.

P multocida infections during pregnancy and in utero transmission have also been reported. [252627]

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.

CLINICAL PRESENTATION


History

A history of animal exposure, whether occupational or recreational, should alert the physician to the possibility of a zoonosis. [28]

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.

Physical

Physical findings of P multocida infection relate to the site of infection, as follows:

  • Local - Erythema, warmth, pain and tenderness, purulent discharge, lymphangitis, joint swelling, decreased range of motion

  • Respiratory - Sinus tenderness, hoarseness, pharyngeal erythema, rales and rhonchi upon chest auscultation, dullness to percussion, changes in vocal fremitus

  • CNS - Focal neurologic deficits, signs of meningeal irritation (eg, nuchal rigidity, Brudzinski sign, Kernig sign)

  • Abdominal - Abdominal tenderness, guarding and rebound, hepatosplenomegaly, costovertebral angle tenderness

  • Ocular - Corneal ulcer, conjunctival injection, decreased visual acuity

  • Cardiovascular - Hypotension, tachycardia, new cardiac murmur, embolic phenomenon

  • Lymph nodes - Regional adenopathy

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

Differential Diagnoses

TREATMENT & MANAGEMENT

Medical Care

Because P multocida infection is mostly encountered in the setting of an injury following an animal bite, physicians must be familiar with the associated microbiological oral flora of certain animals, especially dogs and cats.

Most animal bites are polymicrobial, with both aerobic and anaerobic bacteria. Several species can be isolated at once.

Several Pasteurella species are associated with dog and cat bites, including P multocida subspecies multocida,P multocida subspecies septica, Pasteurella stomatis, and Pasteurelladogmatis. Pasteurella canis is associated only with dog bites.

Other fastidious gram-negative organisms that have been associated with dog and cat bites include Capnocytophaga canimorsus and Capnocytophaga cynodegmi, especially in patients who had undergone previous splenectomy. C canimorsus infection can cause fulminant sepsis and meningitis, whereas C cynodegmi infection usually causes a milder localized inflammation.

Several other organisms are associated with cat bites, including Bartonella henselae, Francisella tularensis, and cowpox virus.

Medical management of animal bite wounds includes local wound care, standard-protocol tetanus prophylaxis, standard-protocol rabies prophylaxis, and either oral or intravenous empiric antimicrobial treatment.

Antimicrobial treatment is discussed in Medication.

Local care of bite wounds includes cleansing and removing nonviable tissue. Gently cleanse the skin surrounding the bite wound with an antiseptic solution. To prevent further tissue injury, do not scrub the wound directly. Soaking is of no benefit, but copious irrigation with a small-gauge catheter on a syringe helps remove debris and decreases the concentration of bacteria in contaminated wounds. Debridement and closure are discussed in Surgical Care.

Surgical Care

The initial assessment of an animal bite includes an estimation of the infection risk. Bites to the head and neck, to the distal extremities, and near joints carry the highest risk of infection. In general, persons with animal bite wounds are at a high risk for infection, especially those who present to medical attention more than 8-10 hours after the injury occurred.

Persons with underlying medical diseases, such as diabetes mellitus, chronic liver disease, asplenia, alcoholism, HIV infection, or other immunodeficiency conditions (including chronic steroid exposure), are at increased risk of infection.

After irrigation and cleansing, sharply débride nonviable tissue to reduce the risk of infection and to allow easier suturing by providing a more even edge.

Primary suturing of bite wounds is reserved for minor injuries, those at low risk for infection, and those that have been treated within 8-10 hours of injury.

Leave all other wounds open until the risk of infection is reduced by cleansing, debridement, and prophylactic antibiotics.

Consultations

See the list below:

  • General surgeon

  • Orthopedic surgeon

Activity

Elevation is of great importance in the management of limb injuries. Lack of elevation may result in excessive edema, which may produce compartment syndrome and compromise local circulation, to the extent of threatening the viability of the limb.

Wounds on extremities should be immobilized and elevated with a sling to reduce edema, which may hamper normal activities.

MEDICATION


Medication Summary

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 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.

The duration of therapy for P multocida infections has not been well established and can be tailored to clinical response. Milder soft-tissue infections usually require 7-10 days of oral therapy. More-severe cases can be treated for 10-14 days. Deep-tissue infections often require 4-6 weeks of treatment, usually with intravenous therapy initially.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Amoxicillin and clavulanate (Augmentin)

Drug combination treats bacteria resistant to beta-lactam antibiotics. For children >3 mo, base dosing protocol on amoxicillin content. Because of different ratios of amoxicillin to clavulanic acid in 250-mg tab (250:125) vs 250-mg chewable tab (250:62.5), do not use 250-mg tab until child weighs >40 kg.

Cefuroxime (Ceftin, Zinacef)

Second-generation cephalosporin that maintains gram-positive activity of first-generation cephalosporins; adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration.

Doxycycline (Vibra-Tabs, Bio-Tab, Doryx, Vibramycin)

Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Penicillin G (Pfizerpen)

Inhibits biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached. Most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Use penicillin VK for PO or penicillin G for IV.

Ampicillin and sulbactam (Unasyn)

Drug combination of beta-lactamase inhibitor with ampicillin. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.

Ticarcillin and clavulanate (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.

Ciprofloxacin (Cipro)

Mode of action of all quinolones involves inhibition of bacterial DNA synthesis by blocking the enzyme DNA gyrase

Amoxicillin (Trimox, Amoxil)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Levofloxacin (Levaquin)

For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

Ampicillin (Principen, Omnipen)

Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication PO.

Piperacillin and tazobactam sodium (Zosyn)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.

Ertapenem (Invanz)

Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by various beta-lactamases including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.

Imipenem and cilastatin (Primaxin)

For treatment of multi-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity.

Minocycline (Dynacin, Minocin)

Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.

Cefoxitin (Mefoxin)

Second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death.

Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Septra, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

Tigecycline (Tygacil)

A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Complicated intra-abdominal infections caused by C freundii, E cloacae, E coli, K oxytoca, K pneumoniae, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible isolates only), S anginosus group (includes S anginosus, S intermedius, and S constellatus), B fragilis, B thetaiotaomicron, B uniformis, B vulgatus, C perfringens, and P micros.