HACEK Group Infections

Updated: Jun 28, 2023
  • Author: Zartash Zafar Khan, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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The acronym HACEK refers to a group of fastidious gram-negative coccobacillary organisms. (Haemophilus species; Actinobacillusactinomycetemcomitans [In 2006 the genus was renamed Aggregatibacter actinomycetemcomitans]; Cardiobacterium hominisikenella corrodens; and Kingella kingae). [1] HACEK microorganisms grow slowly in standard blood culture media, and recovery may require prolonged incubation. 

Identification can be performed by automated systems but performance may be suboptimal. As with many other organisms, MALDI-TOF is emerging as as potential identification technique for the HACEK group.

HACEK organisms typically are oropharyngeal commensals and have long been recognized as a cause of infective endocarditis (IE). [2, 1]  Eikenella and Cardiobacterium species have been recovered from the gastrointestinal tract and female genital tract. [3] In addition to infective endocarditis, these organisms have been known to cause wound infections (particularly of bite wounds), soft-tissue abscess, brain abscess, endophthalmitis, parotitis, periodontitis, empyema and bacteremia without endocarditis, and osteomyelitis. In addition, rare cases of endometritis and urinary tract infection have been identified. Invasive infections commonly occur in the setting of trauma, underlying structural heart disease, malignancy, and other immunocompromised states.



When introduced into healthy tissue, the HACEK group organisms have the potential for invasive disease and abscess formation. The pathogenesis of HACEK endocarditis is thought to be due to colonization of the oropharynx with bacteria that reach the vascular space following either trauma or local infection.

Haemophilus species are pleomorphic gram-negative coccobacilli that require X (hemin) and/or V (nicotinamide adenine dinucleotide) factors for isolation. These substances are found naturally in red blood cells. H parainfluenzae requires NAD (V factor) but not hemin (X factor), in contrast to H influenzae, which requires both. H parainfluenzae is capable of causing a variety of infections such as IE, otitis media, abscesses, and pneumonia, although it is an uncommon cause of these infections. [4] H influenzae on the other hand very rarely causes IE.

 Aggregatibacter actinomycetemcomitans with original genus name, "Actinobacillus," referred to the internal star shapes formed by colonies on solid media. In 2006, the genus was renamed Aggregatibacter, reflecting the propensity of organisms in this genus to grow as discrete clumps (aggregates) in broth culture. It can cause periodontal disease as well as IE. The ability of this organism to produce gingivitis is based in great part on its production of a leukotoxin and its ability to invade gingival cells. Cardiobacterium hominis is very rarely implicated in diseases other than endocarditis. C hominis is found in the oropharynx but rarely the gastrointestinal tract. [4]

Eikenella corrodens, as the name indicates, pits (or corrodes) into the surface of solid agar media. This pitting is associated with the presence of pilins, which may be important for adhesion to host tissue. It exudes a chlorine bleach odor. It is a member of the Neisseriaceae family, however can not be recovered on selective media for Neisseria spp such as Thayer-Martin agar. E corrodens can cause IE and is associated with infection following traumatic inoculation from the oral cavity and is found in up to 42% of abscesses from human bite wounds. [4]

Kingella kingae,also is a member of the Neisseriaceae but unlike Eikenella, it usually can be recovered on Thayer-Martin agar. In comparison to others in the HACEK group, K kingae is isolated from endocarditis infrequently. However, it is a significant cause of osteomyelitis/septic arthritis in children aged 6 months-3 years. The organism also may be transmitted person to person by respiratory droplets, and it caused a 2004 outbreak of septic arthritis in children attending daycare. [5]





Infective endocarditis is a rare disease with an annual incidence of 3 to 10 cases per 100,000 people. [6] The most common IE pathogens in children are gram-positive cocci, especially virulence group α-hemolytic streptococci, staphylococci and enterococci. The HACEK group are responsible for 1-3% of all infective endocarditis. [7] HACEK endocarditis mostly affects patients with underlying heart disease or prosthetic valves, and is characterized by an insidious course, with a mean diagnosis delay of 1 month (Haemophilus spp) to 3 months (Aggregatibacter and Cardiobacterium spp).

In Olmsted County, Minnesota, about 0.14 of every 100,000 people develop HACEK endocarditis each year. Twelvcases occurred in patients with prosthetic valve, and 33 cases occurred and in patients with native valve. [8]

In a prospective multinational cohort study from 64 hospitals in 28 countries, HACEK organisms were isolated in approximately 1.4% of infective endocarditis cases. [2]

For the most part, endocarditis is the focus of incidence studies of HACEK infections, but other infections can be caused by these organisms. By the mid-1980s,132 cases of H aphrophilus infection had been reported: 55% endocarditis, 15% brain abscess, and the remainder sinusitis, meningitis, pneumonitis, bacteremia, and empyema.

Nineteen cases of Eikenella brain infections were reported through 1983. [9]


Infective endocarditis (IE) caused by the HACEK organisms typically is subacute, with the exception of H parainfluenzae endocarditis, which may present more acutely. [10] At the time of presentation, large valvular vegetations are common. Embolization is common and results in significant morbidity.

Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of patients with HACEK endocarditis (HE) were compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs 61 years; p< 0.001), a higher prevalence of immunologic/vascular manifestations (32% vs 20%; p< 0.008) and stroke (25% vs 17% p=0.05) but a lower prevalence of congestive heart failure (15% vs 30%; p=0.004), death in-hospital (4% vs 18%; p=0.001) or after 1 year follow-up (6% vs 20%; p=0.01) than IE due to other pathogens (n=5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34–9.65; p< 0.01) and younger age (OR 0.62; CI 0.49–0.90; p< 0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p< 0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). [11]  

Mortality rates range from 10-40% and may vary by organism. Contemporary case series have suggested a modern mortality risk closer to 10-15%. [8]

The morbidity of IE caused by the HACEK group is similar to that of other types of endocarditis and includes embolization, local extension into the perivalvular area, congestive heart failure (CHF), and regurgitant valve lesions. Compared with all causes of IE, these organisms may be associated with an increased risk of embolization. [12]


No racial differences have been reported in endocarditis caused by the HACEK organisms.


Older data suggest that HACEK endocarditis has a male predominance. However, there is not enough data available to say that, in the modern era, there is a predilection toward either sex. [13]


The great majority of IE cases caused by HACEK organisms have been reported in older adults. HACEK IE in children with congenital heart disease has been reported.

In children, 70% of Kingella infections involve the skeletal system, predominantly septic arthritis. In a study of K kingae infections in children from southern Israel, Yagupsky and Dagan found that 45% of affected children were aged 13-24 months, with an attack rate of 27 cases per 100,000 children younger than 24 months. Almost 90% of all children with invasive K kingae infections have been younger than 5 years. [14]

Actinobacillus is highly associated with dental disease, being found in 50% of adults with periodontitis and 97% of children with juvenile periodontal disease. In a series of 57 cases of A actinomycetemcomitans endocarditis, poor dentition (46%) and abnormal cardiac valves (60%) were found to be predisposing factors. [15]



The prognosis is variable depending on many factors, such as delay in diagnosis, age of the patient, and occurrence of complications. Patients with uncomplicated IE caused by HACEK organisms generally respond well to therapy and have an excellent prognosis. [8]