Pasteurella Multocida Infection

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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. 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. See the image below.


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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.[1] The latter two are particularly common following cat bites because of their small, sharp, penetrative teeth.[2]

Respiratory: P multocida may cause upper respiratory tract infections, including sinusitis, otitis media, mastoiditis, epiglottitis,[3] pharyngitis, and Ludwig angina.[4] In rare cases, P multocida may also cause lower respiratory tract infections, including pneumonia, tracheobronchitis, lung abscess,[5] and empyema,[6] usually in individuals with underlying pulmonary disease.

Cardiovascular: P multocida has been reported to cause native-[7] and prosthetic-valve endocarditis,[8] pericarditis, mycotic aneurysms,[9] vascular graft infections,[10] central venous catheter infections, bacteremia, sepsis, septic shock,[11] and disseminated intravascular coagulation.[12]

Central nervous system: P multocida is an uncommon cause of meningitis,[13] subdural empyema, and brain abscess.[14] P multocida meningitis has been associated with cat licks and bites occurring on the face in persons at the extremes of age.[15]

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.[16]

Ocular: P multocida periocular abscess,[17] conjunctivitis, 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.[18]

Chronic obstructive pulmonary disease is a risk factor for P multocida respiratory tract infection,[19] which carries a mortality rate of approximately 30%. Diabetes mellitus[20] and liver dysfunction[21] are predisposing conditions associated with pasteurellosis and associated bacteremia.

P multocida infections during pregnancy and in utero transmission have also been reported.[22, 23, 24]

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

Physical

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

Causes

Causes of P multocida infection include the following:

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Medical 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.

Consultations

Activity

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 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.

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.

Amoxicillin and clavulanate (Augmentin)

Clinical Context:  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)

Clinical Context:  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)

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

Penicillin G (Pfizerpen)

Clinical Context:  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)

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

Ticarcillin and clavulanate (Timentin)

Clinical Context:  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)

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

Amoxicillin (Trimox, Amoxil)

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

Levofloxacin (Levaquin)

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

Ampicillin (Principen, Omnipen)

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

Piperacillin and tazobactam sodium (Zosyn)

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

Ertapenem (Invanz)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

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

Azithromycin (Zithromax)

Clinical Context:  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)

Clinical Context:  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.

Class Summary

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

Further Outpatient Care

Complications

Prognosis

Author

Sara L Cross, MD, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Assistant Professor, Department of Medical Education, University of Tennessee Health Science Center College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Michael Gelfand, MD, FACP, Chief, Professor, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis, University of Tennessee Health Science Center College of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Larry I Lutwick, MD, Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Aaron Glatt, MD, Chief Administrative Officer, Executive Vice President, Mercy Medical Center, Catholic Health Services of Long Island

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Disclosure: Nothing to disclose.

Additional Contributors

J Robert Cantey, MD Professor, Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina

J Robert Cantey, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Investigation, American Society for Microbiology, Infectious Diseases Society of America, International Society of Travel Medicine, Musculoskeletal Infection Society, Phi Beta Kappa, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Alexandre Lacasse, MD, MSc Internal Medicine Faculty, Assistant Director, Medicine Clinic, Infectious Disease Consultant, St Mary's Health Center

Alexandre Lacasse, MD, MSc is a member of the following medical societies: American College of Physicians, American Medical Association, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose. Thomas Lafeber, MD Consulting Staff, Wellstar Infectious Disease LLC

Thomas Lafeber, MD is a member of the following medical societies: American Medical Association, American Society of Transplantation, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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Pasteurella multocida infection.

Pasteurella multocida infection.