Eikenella, Pasteurella, and Chromobacterium Species

Microbiology

Eikenella, Pasteurella, and Chromobacterium species display both common and contrasting characteristics of laboratory properties, epidemiology, and clinical presentations. Eikenella and Pasteurella spp. are nonmotile, whereas C. violaceum is motile and less fastidious than the others.

E. corrodens was the only recognized species within the genus Eikenella until recently. E. corradens is associated with human infections and belongs to the family Neisseriaceae along with the genera Neisseria and Kingella. E. corrodens is a small, straight rod that can appear coccobacillary . The organism is oxidase-positive and ornithine decarboxylase positive and reduces nitrates to nitrites, but it does not produce catalase, urease, or indole. E. corrodens originally was thought to be related to the strictly anaerobic bacterium Bacteroides ureolyticus (formerly Bacteroides corrodens ) because of the characteristic “corroding” or “pitting” of the surface of blood or chocolate agar by some isolates, suggesting a preference for anaerobic growth. A new species, E. exigua , has been recently recognized, and others are under investigation using sequence-based methods and may lead to distinct, new species. ^,

The genus Pasteurella contains several species of clinical significance and belongs to the family Pasteurellaceae along with the genera Aggregatibacter, Actinobacillus, Haemophilus, and Mannheimia . Most Pasteurella spp. are oxidase and catalase positive, reduce nitrates, and use glucose and a variety of other carbohydrates. Currently, P. multocida , the most important species of human significance, can be separated into the subspecies multocida , septica, and gallicida . P. canis , P dagmatis, and P stomatis are other species isolated from humans. ^{, ,} Several other Pasteurella spp. are rarely if at all associated with human disease. ^{, , ,} Organisms formerly classified as P. gallinarum now are named Avibacterium gallinarum, and some formerly classified as P. haemolytica now are named Mannheimia haemolytica. ^,

The genus Chromobacterium currently contains 2 species of human significance, C. violaceum and C. haemolyticum. The genus is placed in the family Neisseriaceae; other Chromobacterium spp. are recovered from environmental sources and are rarely associated with human infections . Most of these organisms are microaerophilic, facultatively anaerobic, somewhat fastidious, gram-negative bacilli that can appear pleomorphic or coccobacillary in direct smears or smears prepared from culture. C. violaceum is a long, gram-negative, slightly curved bacillus. C. violaceum is positive for catalase, nitrate reductase, and arginine dihydrolase; it grows on sheep blood, MacConkey, chocolate, and Mueller-Hinton agar; and it produces a deep purple pigment (violacein) that can result in black-appearing colonies. The pigment also can be produced during infection, thus resulting in violaceous cellulitis.

Pathophysiology And Epidemiology

E. corrodens is part of the normal flora of the oral cavity, upper respiratory tract, and mucosal surfaces of the gastrointestinal and genitourinary tracts of humans and some mammals. ^, From both a clinical and a laboratory diagnostic perspective, it is useful to discuss E. corrodens in the context of the so-called HACEK group organisms. This mnemonic stands for Haemophilus parainfluenzae , Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus and H. paraphrophilus ), Aggregatibacter (formerly Actinobacillus ) actinomycetemcomitans, Cardiobacterium hominis, E. corrodens, and Kingella kingae and other Kingella spp. As a group, these are slow-growing organisms that often require elevated carbon dioxide concentrations and hemin in the culture medium for optimum growth. HACEK organisms are clinically important in specific disease syndromes, including disseminated diseases, such as subacute bacterial endocarditis and pyogenic arthritis, as well as localized pyogenic diseases of the oral cavity, head, and neck. Compared with the other organisms in the HACEK group, E. corrodens is less fastidious and generally is recoverable within 24–48 hours on routine blood and chocolate agar media. Because of improvements in the composition of broth media and detection techniques, blood cultures from patients with endocarditis suspected to be caused by E. corrodens or other HACEK group organisms generally need not be incubated beyond the routine 5 days used in most laboratories. ^, E. corrodens has a lectin-like protein and multiple pilus proteins on the cell surface that may contribute to adherence to mucosal epithelial cells. Some genes coding for pilus proteins share nucleotide homology, and the pilus proteins show amino acid sequence homology with pilin genes and proteins from Moraxella spp. and Neisseria gonorrhoeae. Other cell surface proteins have the ability to agglutinate red blood cells. The cell wall possesses lipopolysaccharide, and E. corrodens can synthesize an extracellular polysaccharide or slime layer. The organism can trigger inflammation in periodontal tissue that can promote periodontitis. Such virulence factors also may play a role in inhibiting phagocytosis or modulating macrophage activity.

Pasteurella spp. are commensals of the upper respiratory tract, with oropharyngeal carriage found in most dogs and cats, including large cats (lions, tigers, panthers), as well as in swine, rats, opossums, rabbits, fowl, and possibly humans. Pasteurella spp. are primary pathogens of a variety of animals, and several species can cause various human infections, most commonly associated with animal bites or scratches. In a study of 159 human isolates of Pasteurella spp. recovered from dog or cat bites, P. multocida subsp . multocida accounted for 60% of isolates, P. canis for 18%, P. multocida subsp . septica for 13%, P. stomatis for 5%, and P. dagmatis for 3%. Pasteurella also can be acquired through aerosol inhalation, and there may be differences in the propensity of the 2 P. multocida subspecies to cause respiratory tract disease. Although a known animal exposure is present in most human P. multocida infections, 5%–15% of cases of these infections have none. Pasteurella spp. generally can be isolated from culture on blood or chocolate agar within 24–48 hours of incubation; most strains do not grow on MacConkey agar. Gram stain smears of growth on agar reveal small gram-negative coccobacilli. Biochemical identification of P. multocida is straightforward; however, identification of some other Pasteurella species can be difficult. ^{, , ,} Use of conventional biochemical systems such as Vitek (bioMérieux, Inc., Durham, NC) and also matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) are able to identify Pasteurella to the genus level accurately, with MALDI-TOF better able to give accurate species identification.

Studies of virulence factors of Pasteurella spp. have been focused on P. multocida , in which virulence can be associated with the production of neuraminidase and lipopolysaccharide endotoxin. A dermonecrotic toxin, a known virulence factor in animals, can be detected more commonly in strains isolated from adults with chronic bronchitis than from other sources. The best characterized potential virulence factor is P. multocida toxin (PMT), a highly potent mitogen that blocks apoptosis. PMT is thought to be a potential carcinogen, but little evidence exists for its role in human cancer. ^,

C. violaceum is a common saprophyte of soil and water, especially in tropical and subtropical areas. ^, The organism usually gains entry through the skin to cause localized wound infection, but bloodstream and disseminated infection can occur in patients with select immune dysfunction. C . violaceum can be isolated readily from blood, abscess fluid, or purulent drainage, and identification is achievable using commercial systems. C. violaceum is included in MALDI-TOF databases and in the VITEK 2 ID-GNB card. ^, Pigmented and nonpigmented strains can have similar pathogenicity and disease severity. ^, Several virulence factors have been identified including endotoxin, adhesins, invasins, and cytolytic proteins. ^, Chromobacterium haemolyticum , a species newly described in 2008, differs from C. violaceum in that it is nonpigmented and has strong β-hemolytic activity on sheep blood agar. Misidentifications of C. haemolyticum as nonpigmented C. violaceum could occur with currently available biochemical and MALDI-TOF systems; 16S rRNA sequencing is required for definitive identification.

Clinical Manifestations

Most infections caused by E. corrodens involve the head, neck, or respiratory tract or are related to human bites or fist-to-mouth injuries. ^, Localized infections generally are indolent and follow a slowly progressing course, often becoming manifest no earlier than 1 week after injury. E . corrodens is a cause in approximately 25% of infections resulting from clenched fist injuries. These slowly evolving infections can lead to complications such as a stiff joint or, rarely, even amputation. Oral contamination can lead to infection of surgical wounds, such as after craniofacial or esophageal reconstruction. E . corrodens is prevalent in subgingival plaque of adults with periodontitis. Pleuropulmonary infections also can occur, presumably as a result of aspiration of oral contents or leakage of oral secretions into the pleural space after surgical procedures. In these cases, pneumonia, empyema, or pulmonary cavitation can result. E. corrodens often is part of a polymicrobial infection, especially with viridans or β-hemolytic streptococci, staphylococci, and oral anaerobic bacteria in human bites, head and neck infections, respiratory tract infections, and hepatic abscesses. ^, E. corrodens infections occur in immunocompromised people as well as in people with normal immune function. E. corrodens can be found concurrently with Actinomyces spp. and may contribute to the pathogenesis of actinomycosis, ^, and it has also been implicated with Actinomyces spp. in a distinctive clinical infection known as chronic diffuse sclerosing osteomyelitis of the mandible.

E. corrodens also can be recovered from peritoneal cultures after ruptured appendix, gastric operations, traumatic duodenal rupture, gastric cancer, and abscesses of the spleen, liver, and pancreas. Other serious E. corrodens infections include bloodstream infection (BSI), endocarditis, pyogenic arthritis, spondyloarthritis, chorioamnionitis, neonatal sepsis, neonatal conjunctivitis, orbital infections, meningitis, sinusitis, submandibular abscess, thyroiditis, thyroid abscess, renal abscess, and brain abscess. ^, Invasion of the central nervous system can occur by extension from periodontal, middle ear, or sinus infections ( Fig. 152.1 ). BSI and endocarditis most often occur in immunocompromised hosts, intravenous drug abusers, and patients with previous cardiac valve damage. Osteomyelitis of the calcaneus has been reported subsequent to penetration of the heel by a toothpick. Injection and fingerstick site abscesses caused by E. corrodens have been reported in adolescents with insulin-dependent diabetes mellitus; licking or biting skin or nails could provide an opportunity for the organism to contaminate traumatized skin. E. exigua has been isolated from brain abscess, blood, parotid gland, bone, and soft tissue cultures.

Infection with Pasteurella spp., most commonly P. multocida, generally occurs after an animal bite. P. multocida is the pathogen in >50%–75% of infections following a cat bite and in up to 50% of infections following a dog bite ( Fig. 152.2 ). Cat scratches also can be complicated by P. multocida infection. Infection can occur after bite injuries from lions, tigers, or other large cats, as well as rats, rabbits, and other animals. Wound infections caused by P. multocida typically develop rapidly, within 12–24 hours after injury, and manifest with warmth, swelling, redness, and tenderness and with serosanguineous-to-purulent discharge at the site. Regional lymphadenopathy, chills, and fever are common. In a review spanning 10 years, the highest rate of infection occurred in children <5 years of age and in adults >55 years of age. Tenosynovitis and tendon sheath abscess formation, osteomyelitis, and pyogenic arthritis are complications related to the deep penetration by the teeth or claws of the animal. ^, Preexisting joint disease and joint prosthesis can predispose patients to pyogenic arthritis.

Some cases of infection with Pasteurella spp. occur in people with frequent animal exposure but without a bite or scratch injury. These cases include infections of the upper respiratory tract, soft tissue infection secondary to accidental injury, intra-abdominal infections, meningitis, and bone and joint infections. Pneumonia with or without empyema is rare and occurs chiefly in adults with underlying chronic bronchopulmonary disease. P. multocida can cause BSI and meningitis in infants and children, with most cases occurring in infants <12 months of age. Exposure to animals was frequently nontraumatic and typically subsequent to a pet dog or cat licking the infant’s face. The symptoms of central nervous system infection and abnormalities of cerebrospinal fluid in infected children are typical of bacterial meningitis; however, a mononuclear cell predominance in cerebrospinal fluid has been reported. ^{, , ,} BSI is documented in approximately 50% of patients with meningitis. Neurologic sequelae are uncommon. Other P. multocida central nervous system infections include brain abscess secondary to direct penetration of the brain parenchyma after a dog bite, subdural empyema, and ventriculoperitoneal shunt infections. ^,

P. multocida is a rare cause of fetal infection secondary to maternal BSI and invasion through the placenta, although ascending infection also has been postulated. ^, This situation is in contrast to fetal infections in animals, in which Pasteurella spp. are well-documented causes of septic abortion. Neonatal systemic infection with P. multocida has been reported only rarely. The presentation is similar to that of early-onset group B streptococcal disease and is characterized by fulminant septicemia with or without meningitis. Neonatal infection usually occurs in the setting of a maternal obstetric complication, including chorioamnionitis, premature onset of labor, prolonged rupture of membranes, postpartum fever, or premature delivery. ^, The mortality rate is high, particularly in infants who acquire infection in utero and who are symptomatic at birth. The maternal genital tract is the source of the infection for both infant and mother. Genital colonization is thought to occur as a result of hand inoculation after animal contact. ^, Late-onset meningitis and cervical spine osteomyelitis were reported in a 20-day-old infant from a household with 2 pet cats. The infection occurred without an obvious history of cat bites, scratches, or licks. Systemic infections are rare in older children and adults. ^,

People with underlying abnormalities of host defense, especially liver disease, are predisposed to BSI caused by P. multocida infection. ^, Direct trauma from an animal bite or scratch has occurred in some patients, but oropharyngeal colonization secondary to contact with secretions of a pet also can be the source of invasive infection. Septic shock develops in approximately 50% of patients, and the mortality rate approaches 40%. Contiguous spread of infection from liver to lung with involvement of the diaphragm has been reported. P. multocida also has been associated with peritonitis secondary to a ruptured appendix or peritoneal dialysis, endophthalmitis after a cat scratch, prosthetic vascular graft infection, and granulomatous hepatitis. Urinary tract infection caused by P. multocida is rare but has been reported in children with underlying renal disease. ^, Repeated catheterization and skin contamination with P. multocida can contribute to the introduction of the organism into the urinary tract. Possible horizontal transmission has been reported. A case of P. multocida BSI in a patient with Kikuchi disease has been reported, but the relationship between Kikuchi disease and P. multocida infection could not be established. Another case with central line infection was reported in a young adult with a history of cat bite to a dialysis catheter. Several other Pasteurella spp. have been reported as human pathogens. P. canis, P. dagmatis, and P. stomatis have been associated with wound infections and osteomyelitis after cat or dog bites, as well as with endocarditis, peritonitis, and sepsis in a patient with cirrhosis and with septicemia in a diabetic patient. The reservoir of P. canis is the oral cavity of dogs, whereas the latter 2 species have been recovered from the oral cavity of both dogs and cats. P. aerogenes has been associated with animal bite wounds, urinary tract infection, and peritonitis in humans. ^, P. bettyae has been recovered from amniotic fluid, blood (usually in the neonatal period), finger lesions, abscesses, wounds following rectal surgical procedures, and genitourinary lesions, particularly Bartholin gland abscesses. ^, Peritonitis caused by P. aerogenes and P. pneumotropica was reported in a patient undergoing peritoneal dialysis following bites by hamsters. ^,

C. violaceum is a rare human pathogen but is a common soil and water inhabitant in tropical and subtropical areas; most infections are reported from Southeast Asia. ^{, ,} All cases of infection reported in the US have been in the southeast, especially Florida, Georgia, Louisiana, and South Carolina. A review of 106 reported cases between 1952 and 2009 showed that 42% of the patients were <10 years of age, and most patients did not have any predisposing factors. Infections occur primarily in boys or men during the summer months and usually involve injury to the skin in association with exposure to soil or water. Most infections have a short incubation time, but symptoms can occur 60 days after a specific exposure. The initial symptom typically is pain at the wound site. Infection can be limited to the wound, or it can disseminate rapidly, causing overwhelming septicemia with a high mortality rate. ^{, ,} Rapid progression to sepsis with metastatic abscesses to liver, lung, and spleen is striking. Fever, nausea, vomiting, abdominal pain, and diarrhea frequently are noted. Septic shock, pneumonia, osteomyelitis, lymphadenitis, diarrhea, urinary tract infection, conjunctivitis, orbital cellulitis, and abscesses of spleen, lung, brain, and liver have been described. ^, Pneumonia after aspiration of fresh warm water was reported in 2 cases of near drowning. Multiple sites of abscesses tend to occur, especially in the liver, spleen, and lungs. Healthcare-associated infections and pneumonia have been reported. Infections can recur. Although most infections have occurred in people presumed to be immunologically competent, chronic granulomatous disease predisposes to C. violaceum infection. One review suggested that patients with chronic granulomatous disease may have lower rates of bacteremia and death than patients without chronic granulomatous disease. Similarities have been observed in clinical presentations of C. violaceum infection and the septicemic form of melioidosis caused by Burkholderia pseudomalleii , which is also seen mostly in Southeast Asia. Diagnosis is made by culture of wound exudate, biopsy specimen, blood, or abscess fluid.

C. haemolyticum has been reported to cause pediatric bacteremia, proctocolitis in children, pneumonia, and necrotizing fasciitis. ^{, ,}

Treatment And Prevention