HACEK is an acronym consisting of the first initial of  each genus represented in the group: Haemophilus spp., especially H. aphrophilus

Actinobacillus actinomycetemcomitans

Cardiobacterium hominis

Eikenella corrodens

Kingella spp.

Members of this group of gram-negative bacilli have in common the need for an environment with increased CO2(capnophilic). Unlike Haemophilus spp., the latter four members of the HACEKgroup are considered to be more dysgonic (slower or poorer growing).

Their predilection for attachment to heart valves, usually damaged or prosthetic, makes many of them

an important cause of endocarditis. Endocarditis most commonly involves the heart valves; the lesion (referred

to as vegetation) is composed of fibrin, platelets, polymorphonuclear cells, monocytes, and microorganisms.

Additional organisms that make up the majority of cases of endocarditis are the viridans group of streptococci (most common after 1 year of age), S. aureus, S. pneumoniae, the coagulase-negative staphylococci, the so-called “nutritionally variant streptococci” (Abiotrophia spp.), and enterococci.

Members of the HACEK group include both fermentative and nonfermentative, gram-negative bacilli. All of the members can be normal flora of the oral cavity, allowing for their introduction in the bloodstream and resultant infections. All members are opportunists and generally require a compromised host. Risk factors for infective (bacterial) endocarditis include tooth extraction, history of endocarditis, gingival surgery, heart valve surgery, and mitral valve prolapse. Table 19-4 summarizes the key reactions and characteristics of HACEK and Capnocytophaga spp.


Haemophilus aphrophilus

Haemophilus aphrophilus (Gr aphros: “foam loving” or needing high concentration of CO2) is described in the

beginning of this chapter and is not further discussed here. Figures 19-12 and 19-13 illustrate the colonial and

microscopic morphology of H. aphrophilus

Actinobacillus actinomycetemcomitans

Actinobacillus actinomycetemcomitans is a member of a genus that includes animal pathogens or animal endogenous flora that in general does not routinely cause infections in humans. The organism was given

the name actinomycetemcomitans because it was isolated with Actinomyces in a polymicrobic infection.

Six species of Actinobacillus have been recovered from humans. Human tissue infections attributed to cattle,

sheep, pig, and horse bites, or through contact with these animals have occurred. All members of the genus are small rods to coccoid gram-negative bacilli (Figure 19-14) that are nonmotile

A. actinomycetemcomitans is divided into five serotypes based on its surface polysaccharides, of which a, b, and c are the most common. A. actinomycetemcomitans is found as normal oral flora in humans. Clinically it has been isolated from blood, lung tissue, abscesses of the mouth and brain, and sinuses. However, it has been isolated from the blood as the causative agent of subacute bacterial endocarditis with an insidious and protracted presentation. In fact, of the HACEK group, it is the most common cause of endocarditis. Individuals with juvenile periodontal disease or other dental disease harbor the organism where it can cause destruction of the

alveolar bone that supports the teeth. Major virulence factors include collagenase and a leukotoxin that is toxic to polymorphonuclear cells and monocytes.

A. actinomycetemcomitans is fastidious, as are all members of the HACEK group, requiring increased CO2 at least for initial isolation from clinical specimens.

It is a fermenter, although the addition of serum to the carbohydrate containing tubes is often necessary to demonstrate fermentation. The isolates may require more than 24 hours for visible growth; a distinctive “star shape” in the center of the colonies is often seen at 48 hours. The star shape is best observed after 48 hours by using lOOx magnification under a light microscope, when subcultured to a clear medium,

or a stereo microscope at the highest magnification  available. Figure 19-15 depicts the colony morphology  In broth, the organism is granular and may adhere to the sides of the tube. Isolates are catalase positive and oxidase variable, do not grow on MacConkey agar, and are negative for urease, indole, esculin, and citrate. A. actinomycetemcomitans is the only species in the genus that is typically urease negative. Glucose fermentation is positive (with or without gas), and fermentation of xylose, mannitol, and maltose are variable. The isolates do not ferment lactose or sucrose.

A. actinomycetemcomitans demonstrates sensitivity to penicillin in vitro, although this agent is not always successful clinically. In addition, isolates are susceptible to aminoglycosides, third-generation cephalosporins, quinolones, chloramphenicol, and tetracycline. Resistance is common to vancomycin and erythromycin.

Usual treatment for endocarditis is with penicillin and an aminoglycoside.


Cardiobacterium hominis

Cardiobacterium hominis, a pleomorphic, nonmotile, fastidious, gram-negative bacillus, is normal flora of FIGURE 19-16 . The 48-hour growth of colonies of Cardiobacterium hominis on sheep blood agar.

FIGURE 19-17 . Gramstain of Cardiobacteriumshowing typical “rosettes” (1 OOOx). Hominis the nose, mouth, and throat and may be present in the gastrointestinal tract. Oral infections or dental procedures usually precede the endocarditis. The usual clinical manifestation is that of endocarditis, often presenting with very large vegetations and no demonstrable fever. It infects the aortic valve more frequently than the other HACEKs. Rarely, C. hominis has been associated with meningitis.

Gram stains of the bacilli often show false grampositive reactions. The organisms tend to form rosettes, swellings, and, in yeast extract, sticklike structures.

They grow on SBA and CHOC but not on MacConkey agar. Figures 19-16 and 19-17 illustrate the colonial and

microscopic morphology. On agar, pitting may be produced. C. hominis is a fermenter, but as with A. actinomycetemcomitans, reactions may be weak, and serum may be needed to enhance them. C. hominis

ferments glucose, mannitol, sucrose (unlike A. actinomycetemcom, itans) and maltose. Isolates are oxidase

positive, catalase negative, and indole positive, the latter two traits helping to further differentiate them from Actinobacillus spp. They are negative for urease, nitrate, gelatin, and esculin. Sensitivity can be seen to f) Iactams, chloramphenicol, and tetracycline with variable response to aminoglycosides, erythromycin, clindamycin, and vancomycin. Usual modes of therapy include penicillin and an aminoglycoside.


Eikenella corrodens

Eikenella corrodens is a member of the usual flora of the oral and bowel cavities. Most infections associated with this organism have been mixed and often occur as a result of trauma, especially after human bites or

fights (Le., “clenched fist wounds,” or after the skin has been broken by human teeth). Poor dental hygiene or

oral surgery has also been associated with infections.

£. corrodens has been reported as the cause of meningitis, empyema, pneumonia, osteomyelitis, arthritis, and postoperative tissue infections. In drug addicts, it has been implicated in cellulitis as a result of direct inoculation of the organisms into the skin after oral contamination of needle paraphernalia (because of licking the needle clean instead of sterilizing).

E. corrodens shows a predilection for attachment to heart valves and thus cause endocarditis, although it is the least common isolate of the HACEK group in adult infectious endocarditis.

£. corrodens isolates are fastidious, gram-negative coccobacilli that grow best under conditions of increased CO2 with hemin. They are nonmotile, oxidase positive, and asaccharolytic and therefore are very similar to the Moraxella spp. Unlike the latter, however, they are catalase negative and often produce a yellow pigment.

About 45‘X, of the isolates of £. corrodens pit or corrode the surface of the agar. Figures 19-18 and 19-19

illustrate the colonial and microscopic morphology.

In broth medium, they may adhere to the sides of the tube and produce granules. A bleachlike odor from the agar surface may be obvious. They do not usually grow on MacConkey or eosin-methylene blue agar, and they are lysine and ornithine decarboxylase positive and arginine dehydrolase negative. Typically, they are resistant to clindamycin and the aminoglycosides.

In vitro, isolates demonstrate sensitivity to penicillin, ampicillin, cefoxitin, chloramphenicol, carbenicillin,

and imipenem.



Members of the genus Kingella are coccobacillary to short rods with squared ends that occur in pairs or short chains (Figure 19-20). They are typically nonmotile but may demonstrate “twitching” motility. They are nutritionally fastidious, oxidase-positive, catalasenegative fermenters of glucose and other sugars. They colonize the upper respiratory tract, especially the tonsils. Viral infections can be a precursor to infections by these organisms. Poor dental hygiene or oral surgery is associated with infection. The genus consists of three species: Kingella den itrificans , Kingella kingae, and Kingella ora/is.

K. denitrificans may grow on Thayer-Martin medium and, if it does not pit the agar as many strains do, may resemble Neisseria gonorrhoeae. Gram stain morphology of a rod with square ends and in chains

should aid in distinguishing Kingella spp. from N. gonorrhoeae. K. denitrificans is positive for glucose fermentation and nitrate reduction and may grow at 42° C. Unlike Neisseria, K. denitrificans is both catalase and superoxol negative. It is negative for urease, indole, esculin, gelatin, and citrate and does not grow on MacConkey agar. This species is rarely isolated as a pathogen but has been associated with bacteremia and abscesses.

K. kingae weakly ferments glucose and maltose but is negative for sucrose. Unlike other Kingella spp., it may produce a yellow-brown pigment. K. kingae has two types of colony morphologies: a spreading, corroding colony or a smooth, convex, and (3-hemolyticcolony. It is biochemically inactive. Isolates have been obtained clinically from blood, bone, joint fluid, urine, and wounds. Most isolates are from joint and bone infections in children younger than 5 years old; in adults, endocarditis predominates. Isolates of Kingella are usually susceptible to most agents, including penicillin.

figure 19-18 figure 19-19 figure 19-20 table 19-4 figure 19-12 figure 19-13 figure 19-14 figure 19-15 figure 19-16 figure 19-17