HACEK Group Infections

Updated: Sep 27, 2018
  • 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. HACEK stands for Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species. The HACEK group accounts for approximately 5%-10% of community-acquired native-valve endocarditis cases in patients who do not use intravenous drugs. [1] HACEK microorganisms grow slowly in standard blood culture media, and recovery may require prolonged incubation.

HACEK organisms are typically oropharyngeal commensals and have long been recognized as a cause of infective endocarditis (IE). [2] Eikenella and Cardiobacterium species have been recovered from the gastrointestinal tract and female genital tract. [3] In addition to infective endocarditis, these organisms have also 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 abscess formation and invasive disease. In addition, many examples produce vegetations on infected cardiac valves that are complicated by macroemboli. These vegetations are due to the intrinsic properties of the organisms themselves, the significant delay in diagnosis, or a combination of these two factors. Sixty percent of cases of HACEK IE are associated with various types of dental pathology.

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. Haemophilus species are responsible for 0.5%-1% of all cases of IE. Of those, most are due to Haemophilus aphrophilus, followed by Haemophilus parainfluenzae. Haemophilus influenzae rarely causes IE despite its frequency of being involved in bacteremias. Ten percent of cases involve a second pathogen, usually an alpha-hemolytic Streptococcus or Staphylococcus aureus. Endocarditis due to H parainfluenzae has been increasing in frequency. Of these cases, 45% are associated with oral pathology and 10% are associated with upper respiratory tract infections. In 67% of cases, the mitral valve is involved, and in 17%, the aortic valve is involved. Fifty percent of patients have underlying valvular disease.

Thirty-three percent of cases of H aphrophilus IE are due to dental disease, and 20% are due to sinusitis or otitis media. The mitral valve is involved in 56% of patients, and the aortic valve is involved in 33%. Eighty-eight percent of individuals have underlying cardiac disease. Arterial embolization occurs in 31% of cases of H aphrophilus IE.

Actinobacillus actinomycetemcomitans was first isolated in 1912 from skin lesions associated with Actinobacillus israelii. Growth of this bacillus occurs in trypticase soy broth, where it forms granules that float on top or stick to the container. It is the etiologic agent of localized juvenile periodontitis, one manifestation of early-onset periodontitis (EOP).

EOP includes a spectrum of entities in which severe periodontal attachment loss occurs in children, adolescents, and young adults. 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. A actinomycetemcomitans, on its own, can mimic most of the clinical syndromes caused by A israelii. Of patients with A actinomycetemcomitans IE, 86% have underlying heart disease and 25% have infection of a prosthetic valve (usually aortic). The aortic valve is involved in 65%, and the mitral valve is involved in 30%. Arterial embolization occurs in 43% of cases.

As opposed to the other members of the HACEK group, C hominis has been isolated almost exclusively from patients with endocarditis. In addition to being part of the normal flora of the mouth and upper airway, it is isolated from the large bowel. However, most C hominis bloodstream infections are secondary to oral pathology. They are gram-negative or gram-variable pleomorphic rods with bulbous swelling of both ends that are characteristically grouped in chains, clusters, or rosettes. Seventy-five percent of cases have underlying heart disease, with 43% involving the mitral valve and 36% the aortic valve. Arterial embolization is documented in 40% of patients.

E corrodens takes its name from its ability to corrode (or pit) the agar during growth. It is a gram-negative pleomorphic, often coccobacillary, rod that exudes a chlorine bleach odor. It is facultatively anaerobic. It is part of the oral flora and many other mucosal surfaces.

E corrodens is usually isolated with other organisms, especially strains of streptococci. This organism is a well-recognized cause of cellulitis resulting from human bites and clenched-fist injuries. It has also been found to be a common cause of soft-tissue infections and endocarditis in drug users. This association may arise from the habit of intravenous drug abusers to lick their needles for good luck. These infections are often complicated by osteomyelitis of the underlying bones. It may produce various pulmonary infections (eg, empyema, pneumonia, septic emboli) that mimic those caused by strict anaerobes. Most patients with E corrodens endocarditis have underlying valve lesions. Compared to cases of IE caused by the other members of the HACEK group, the valvular infections of E corrodens are usually due to intravenous drug abuse.

Kingella species are small gram-negative organisms whose shapes range from those of cocci to those of coccobacilli. This organism can also cause pitting of the agar. The Kingella genus includes 3 species: Kingella kingae, Kingella denitrificans, and Kingella indologenes. IE is usually caused by K kingae. Only approximately 20 cases of endocarditis have been described. Unlike with the other HACEK organisms, Kingella IE progresses quite rapidly.




United States

HACEK organisms are responsible for a small but recognizable percentage (roughly 3%) of endocarditis cases. [4] It is apparent that non-HACEK gram-negative endocarditis is likely increasing in incidence owing to the increased use of endovascular devices. [5] Reporting of these infections has increased, but this may be due simply to increased awareness of the infections among physicians and laboratory personnel, along with new laboratory techniques. Mayo Clinic data suggest the incidence of the HACEK group endocarditis to be 0.14 per 100,000 patient-years. [6]


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. [7]


Infective endocarditis (IE) caused by the HACEK organisms is typically subacute, with the exception of H parainfluenzae endocarditis, which may present more acutely. [8] At the time of presentation, large valvular vegetations are common. Embolization is common and results in significant morbidity.

Mortality rates range from 10%-40% and may vary by organism. Contemporary case series have suggested a modern mortality risk closer to 10%-15%. [6]

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. [9]


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. [10]


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. [11]

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. [12]



The prognosis is quite 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. [6]