Actinobacillus, Aggregatibacter, Kingella, Cardiobacterium, Capnocytophaga, and Similar Organisms

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Actinobacillus, Aggregatibacter, Kingella, Cardiobacterium, Capnocytophaga, and Similar Organisms

Genera and Species to Be Considered

Current Name Previous Name
Actinobacillus spp., including  
A. suis (pigs)  
A. lignieresii (sheep and cattle)  
A. hominis  
A. equuli (horses and pigs)  
A. ureae  
Aggregatibacter sp. (newly proposed)  
A. actinomycetemcomitans Formerly Actinobacillus actinomycetemcomitans
A. aphrophilus Formerly Haemophilus aphrophilus, H. paraphrophilus
A. segnis Formerly Haemophilus segnis
Capnocytophaga canimorsus (dogs and cats) CDC group DF-2
Capnocytophaga cynodegmi (dogs and cats) CDC group DF-2
Capnocytophaga haemolytica  
Capnocytophaga granulosa  
Capnocytophaga leadbetteri  
Capnocytophaga genospecies AHN8471  
Cardiobacterium hominis  
Cardiobacterium valvarum  
Dysgonomonas gadei  
Dysgonomonas mossii  
Dysgonomonas hofstadii  
Dysgonomonas capnocytophagoides CDC group DF-3
Kingella denitrificans  
Kingella kingae  
Kingella oralis  
Kingella potus  

General Characteristics

The organisms discussed in this chapter are dysgonic—that is, they grow slowly (48 hours at 35° to 37° C) or poorly. Although they all ferment glucose, their fastidious nature requires that serum be added to the basal fermentation medium to enhance growth and detect fermentation byproducts. These bacteria are capnophiles—that is, they require additional carbon dioxide (5% to 10% CO2) for growth, and most species will not grow on MacConkey agar. Actinobacillus actinomycetemcomitans has been reclassified to be included in the Aggregatibacter genus based on 16sRRNA sequencing. Haemophilus aphrophilus and Haemophilus paraphrophilus have been reclassified as a single species based on multilocus sequence analysis. Aggregatibacter aphrophilus now includes both the hemin-dependent and hemin-independent isolates. Haemophilus segnis has been reclassified as Aggregatibacter segnis. A. segnis requires V-factor, but does not require X-factor.

Epidemiology, Pathogenesis, and Spectrum of Disease, and Antimicrobial Therapy

The organisms listed in Table 31-1 are part of the normal flora of the nasopharynx or oral cavity of humans and other animals and are parasitic. Species associated with animals are specifically indicated in the table at the beginning of the chapter. As such, they generally are of low virulence and, except for those species associated with periodontal infections, usually only cause infections in humans after introduction into sterile sites following trauma such as bites, droplet transmission from human to human, sharing paraphernalia, or manipulations in the oral cavity. Cardiobacterium spp. are not only associated with the human oropharynx and oral cavity, but they may also be identified in the gastrointestinal and urogenital tract. The natural habitat for Dysgonomonas is unknown. Rare isolates have been identified in the feces of immunocompromised patients.

TABLE 31-1


Organism Habitat (Reservoir) Mode of Transmission
Aggregatibacter actinomycetemcomitans Normal flora of human oral cavity Endogenous; enters deeper tissues by minor trauma to mouth, such as during dental procedures
Actinobacillus spp. Normal oral flora of animals such as cows, sheep, and pigs; not part of human flora Rarely associated with human infection; transmitted by bite wounds or contamination of preexisting wounds during exposure to animals
Kingella spp. Normal flora of human upper respiratory and genitourinary tracts Infections probably caused by patient’s endogenous strains
Cardiobacterium hominis and Cardiobacterium valvarum Normal flora of human upper respiratory tract Infections probably caused by patient’s endogenous strains
Capnocytophaga gingivalis, Capnocytophaga ochracea, Capnocytophaga sputigena, and other species Subgingival surfaces and other areas of human oral cavity Infections probably caused by patient’s endogenous strains
Capnocytophaga canimorsus and Capnocytophaga cynodegmi Oral flora of dogs Dog bite or wound (scratch), long exposure to dogs Capnocytophaga cynodegmi
Dysgonomonas capnocytophagoides and other species Uncertain; possibly part of human gastrointestinal flora Uncertain; possibly endogenous

The types of infections caused by these bacteria vary from periodontitis to endocarditis (Table 31-2). Actinobacillus spp. cause granulomatous disease in animals and have been associated with soft tissue infection in humans following animal bites. Additionally, A. equuli and A. suis have been isolated from the human respiratory tract. Additional species have been isolated from patients that have developed meningitis following trauma or surgery. Actinobacillus spp. may harbor a pore-forming protein toxin known as an RTX toxin that is cytotoxic and hemolytic. A. actinomycetemcomitans is often associated with periodontitis. Virulence factors include the RTX leukotoxin, cytotoxic distending toxin, and the EmaA adhesin. Three of these organisms, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, and Kingella spp., are the A, C, and K, respectively, of the HACEK group of organisms that cause slowly progressive (i.e., subacute) bacterial endocarditis, soft tissue infections, and other infections. Capnocytophaga are associated with septicemia and endogenous infections in immunocompromised patients. Infections with C. canimorsus and C. cynodegmi following a dog or cat bat can result in serious illness including disseminated intravascular coagulation, renal failure, shock, and hemolytic-uremic syndrome. Kingella spp. can also be involved in other serious infections involving children, especially osteoarthritic infections. The pathogenic mechanisms are unknown, and disease associated with Dysgonomonas spp. is quite variable and includes diarrhea, bacteremia, blood, and wound infections.

TABLE 31-2

Pathogenesis and Spectrum of Diseases

Organism Virulence Factors Spectrum of Diseases and Infections
Aggregatibacter spp. Unknown; probably of low virulence; an opportunistic pathogen A. actinomycetemcomitans has been associated with destructive periodontitis that may cause bone loss or endocarditis; endocarditis, often following dental manipulations; soft tissue and human bite infections, often mixed with anaerobic bacteria and Actinomyces spp.; A. aphrophilus is an uncommon cause of endocarditis and is the H member of the HACEK group of bacteria associated with slowly progressive (subacute) bacterial endocarditis
Actinobacillus spp. Unknown for human disease; probably of low virulence Rarely cause infection in humans but may be found in animal bite wounds, such as meningitis or bacteremia; association with other infections, such as meningitis or bacteremia, is extremely rare and involves compromised patients
Kingella spp. Unknown; probably of low virulence; opportunistic pathogens Endocarditis and infections in various other sites, especially in immunocompromised patients; K. kingae associated with blood, bone, and joint infections of young children; periodontitis and wound infections
Cardiobacterium hominis Unknown; probably of low virulence Infections in humans are rare; most commonly associated with endocarditis, especially in persons with anatomic heart defects
Capnocytophaga gingivalis, Capnocytophaga ochracea, and Capnocytophaga sputigena Unknown; produce wide variety of enzymes that may mediate tissue destruction Most commonly associated with periodontitis and other types of periodontal disease; less commonly associated with bacteremia in immunocompromised patients
Capnocytophaga canimorsus and Capnocytophaga cynodegmi Unknown Range from mild, local infection at bite site to bacteremia culminating in shock and disseminated intravascular coagulation; most severe in splenectomized or otherwise debilitated (e.g., alcoholism) patients but can occur in healthy people; miscellaneous other infections such as pneumonia, endocarditis, and meningitis may also occur
Dysgonomonas capnocytophagoides and other species Unknown; probably of low virulence Role in disease is uncertain; may be associated with diarrheal disease in immunocompromised patients; rarely isolated from other clinical specimens, such as urine, blood, and wounds

Infections are frequently treated using β-lactam antibiotics, occasionally in combination with an aminoglycoside (Table 31-3). β-lactamase production has been described in Kingella spp., but the impact of this resistance mechanism on the clinical efficacy of beta-lactams is uncertain. When in vitro susceptibility testing is required, Clinical and Laboratory Standards Institute (CLSI) document M45 does provide guidelines for testing A. actinomycetemcomitans, Cardiobacterium spp., and Kingella spp.

TABLE 31-3

Antimicrobial Therapy and Susceptibility Testing

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Organism Therapeutic Options Potential Resistance to Therapeutic Options Validated Testing Methods*
Aggregatibacter actinomycetemcomitans No definitive guidelines; for periodontitis, debridement of affected area; potential agents include ceftriaxone, ampicillin, amoxicillin-clavulanic acid, fluoroquinolone, or trimethoprim-sulfamethoxazole; for endocarditis, penicillin, ampicillin, or a cephalosporin (perhaps with an aminoglycoside) may be used Some strains appear resistant to penicillin and ampicillin, but clinical relevance of resistance is unclear See CLSI document M45
Actinobacillus spp. No guidelines (susceptible to extended-spectrum cephalosporins and fluoroquinolones) Unknown (same as Aggregatibacter) Not available
Kingella denitrificans, Kingella kingae A beta-lactam with or without an aminoglycoside; other active agents include erythromycin, trimethoprim/ sulfamethoxazole, and ciprofloxacin