HACEK Organisms and associated Infective Endocarditis

HACEK: The acronym HACEK refers to a grouping of gram-negative bacilli: 
  1. Haemophilusspecies (Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus paraphrophilus),
  2. Actinobacillus actinomycetemcomitans, 
  3. Cardiobacterium hominis, 
  4. Eikenella corrodens, and 
  5. Kingella species. 

These organisms share an enhanced capacity to produce endocardial infections and are responsible for approximately 3% of cases of native valve infective endocarditis (IE). They are also the most common cause of gram-negative endocarditis among persons who do not abuse intravenous drugs.
These organisms are found as part of the normal human oral flora. 
Because of their fastidious and slow growth, they are often a cause of culture-negative endocarditis.
In addition to cardiac valve infections, this group is also a cause of other infections, including 
  • periodontal infections, 
  • bacteremia, 
  • abscesses, 
  • peritonitis, 
  • otitis media, 
  • conjunctivitis, 
  • pneumonia, 
  • septic arthritis, 
  • osteomyelitis, 
  • urinary tract infections, 
  • wound infections, and 
  • brain abscess.


1. Haemophilus species are pleomorphic gram-negative coccobacilli that require X (hemin) and/or V (nicotinamide adenine dinucleotide) factors for isolation (growth in culture media). These substances are found naturally in red blood cells. They are responsible for 0.5%-1% of all cases of IE. Of those, 40% are due to H aphrophilus, followed by H parainfluenzae. H influenzae rarely causes IE. The mitral valve is involved in 67% cases, and the aortic valve is involved in 17% cases. Fifty percent of patients have underlying valvular disease.
2. A 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). 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.
3. 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.
4. 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.
5. 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.
Clinical Features:
  • Most cases of infective endocarditis (IE) caused by the HACEK organisms are subacute. Some cases have been present for as long as 18 months before the correct diagnosis is made.
  • Fever is common but may be absent in elderly individuals, immunocompromised patients, or patients taking anti-inflammatory drugs. In some series, it was present in only 50% of cases.
  • Nonspecific symptoms, such as weight loss, anorexia, nausea and vomiting, fatigue, back pain, and night sweats, are common and may lead to a delay in diagnosis.
  • Patients may have a history of prior valvular disease.
  • A history of prior dental, urologic, and other procedures should be elicited.
  • A history of intravenous drug abuse should be elicited.
  • A sentinel headache may indicate the impending rupture of a mycotic aneurysm.

Physical Findings

  • Heart: A new or changing heart murmur is the most consistent physical finding, but it may be absent, especially in right-sided endocarditis.
  • Peripheral
    • Clubbing (with or without hypertrophic osteoarthropathy), splinter hemorrhages, mucocutaneous petechiae, Osler nodes, Janeway lesions, and Roth spots may be seen.
    • Splenomegaly is common.
  • Embolic complications
    • Emboli to the CNS often presents as a focal neurological deficit or a stroke. Emboli to the frontal lobe may be more subtle, causing personality changes or loss of inhibition.
    • Emboli to the kidney may cause flank tenderness, hematuria, and/or oliguria.
    • Embolization to heart vessels can have various manifestations, including acute myocardial infarction and arrhythmia.
    • A large mesenteric embolus can cause bowel ischemia and thus manifest as abdominal pain and tenderness.
    • A right-sided vegetation can embolize to the lung and present similarly to a pulmonary embolus or focal pneumonia.


  • Appropriate antibiotic therapy is central to the management of infective endocarditis (IE) caused by the HACEK organisms (see Medications).
    • beta-lactam antibiotics were the drugs of choice for HACEK infections. However, recent data suggest that beta-lactam resistance is prevalent and that broader-spectrum agents are needed for initial therapy. Based on Infectious Diseases Society of America (IDSA)–endorsed guidelines, ceftriaxone and ampicillin-sulbactam are excellent initial choices.
    • In the case of beta-lactam allergy, a fluoroquinolone (eg, ciprofloxacin, levofloxacin, moxifloxacin) may be used.Complications that arise (eg, heart failure, embolic complications) also require supportive medical therapy.
Surgical Care: May be considered in
    • Refractory CHF
    • One or more embolic episode
    • Uncontrolled infection (persistently positive blood cultures after 1 week of therapy)
    • Physiologically significant valve dysfunction as demonstrated by echocardiography: According to the American Heart Association Committee on IE, criteria associated with an increased need for surgical intervention include (1) persistent vegetations after a major systemic embolic episode; (2) anterior mitral valve vegetations larger than 1 cm in diameter; (3) increase in size of vegetations after 1 month of therapy; (4) periannular extension of infection; and (5) valvular dysfunction, perforation, or rupture.
    • Ineffective antimicrobial therapy (usually not the case with HACEK organisms)
    • Resection of mycotic aneurysms
    • Most cases of prosthetic valve endocarditis caused by more resistant organisms (eg, methicillin-resistant S aureus [MRSA], vancomycin-resistant enterococci [VRE], enteric gram-negative bacilli)
    • Local suppurative complications including perivalvular or myocardial abscess


    • 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.

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