HACEK organisms are a group of fastidious, slow-growing, gram-negative bacteria the growth of which requires an atmosphere of carbon dioxide. Species belonging to this group include several Haemophilus species, Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. HACEK bacteria normally reside in the oral cavity and have been associated with local infections in the mouth. They are also known to cause severe systemic infections—most often bacterial endocarditis, which can develop on either native or prosthetic valves (Chap. 124).
In large series, up to 3% of cases of infective endocarditis are attributable to HACEK organisms, most often A. actinomycetemcomitans, Haemophilus species, and C. hominis. Invasive infection typically occurs in patients with a history of cardiac valvular disease, often in the setting of a recent dental procedure, nasopharyngeal infection, or tongue piercing or scraping. The aortic and mitral valves are most commonly affected. The clinical course of HACEK endocarditis tends to be subacute; however, embolization is common. The overall prevalence of major emboli associated with HACEK endocarditis ranges from 28% to 71% in different series. On echocardiography, valvular vegetations are seen in up to 85% of patients. The vegetations are frequently large, although vegetation size has not been directly correlated with the risk of embolization. Cultures of blood from patients with suspected HACEK endocarditis may require up to 30 days to become positive, and the microbiology laboratory should be alerted when a HACEK organism is being considered. However, most cultures that ultimately yield a HACEK organism become positive within the first week, especially with improved culture systems such as BACTEC. In addition, polymerase chain reaction techniques (e.g., of cardiac valves) are facilitating the diagnosis of HACEK infections. Because of the organisms' slow growth, antimicrobial testing may be difficult, and β-lactamase production may not be detected. E-test methodology may increase the accuracy of susceptibility testing.
Haemophilus species are differentiated by their in vitro growth requirements for X factor (hemin) and V factor (nicotinamide adenine dinucleotide). H. aphrophilus requires only X factor for growth, while species designated para- require only V factor. H. aphrophilus and H. parainfluenzae are the Haemophilus species most commonly isolated from cases of HACEK endocarditis; H. paraphrophilus is less common. Of patients with HACEK endocarditis due to Haemophilus species, 60% have been ill for <2 months before presentation, and 19–50% develop congestive heart failure. Mortality rates as high as 30–50% were reported in older series; however, more recent studies have documented mortality rates of <5%. H. aphrophilus also causes invasive bone and joint infections, and H. parainfluenzae has been isolated from other infections, such as meningitis; brain, dental, and liver abscess; pneumonia; and septicemia.
A. actinomycetemcomitans can be isolated from soft tissue infections and abscesses in association with Actinomyces israelii. Typically, patients who develop endocarditis with A. actinomycetemcomitans have severe periodontal disease or have recently undergone dental procedures in the setting of underlying cardiac valvular damage. The disease is insidious; patients may be sick for several months before diagnosis. Frequent complications include embolic phenomena, congestive heart failure, and renal failure. A. actinomycetemcomitans has been isolated from patients with brain abscess, meningitis, endophthalmitis, parotitis, osteomyelitis, urinary tract infection, pneumonia, and empyema, among other infections.
C. hominis primarily causes endocarditis in patients with underlying valvular heart disease or with prosthetic valves. This organism most frequently affects the aortic valve. Many patients have signs and symptoms of long-standing infection before diagnosis, with evidence of arterial embolization, vasculitis, cerebrovascular accidents, immune complex glomerulonephritis, or arthritis at presentation. Embolization, mycotic aneurysms, and congestive heart failure are common complications. A second species, C. valvarum, has now been described in association with endocarditis.
E. corrodens is most frequently recovered from sites of infection in conjunction with other bacterial species. Clinical sources of E. corrodens include sites of human bite wounds (clenched-fist injuries), endocarditis, soft tissue infections, osteomyelitis, head and neck infections, respiratory infections, chorioamnionitis, gynecologic infections associated with intrauterine devices, meningitis and brain abscesses, and visceral abscesses.
Because of improved microbiologic methodology, isolation of K. kingae is increasingly common. Inoculation of clinical specimens (e.g., synovial fluid) into aerobic blood culture bottles enhances recovery of this organism. Specific real-time PCR studies of joint fluid can identify K. kingae in culture-negative cases. Invasive K. kingae infections with bacteremia are associated with upper respiratory tract infections and stomatitis in 80% of cases. Rates of oropharyngeal colonization with K. kingae are highest in the first 3 years of life, coinciding with increased incidence of skeletal infections due to this organism. K. kingae bacteremia can present with a petechial rash similar to that seen in Neisseria meningitidis sepsis.
Infective endocarditis, unlike other infections with K. kingae, occurs in older children and adults. The majority of patients have preexisting valvular disease. There is a high incidence of complications, including arterial emboli, cerebrovascular accidents, tricuspid insufficiency, and congestive heart failure with cardiovascular collapse.
Treatment: Endocarditis Caused by HACEK Organisms
See Table 146-1. Native-valve endocarditis should be treated for 4 weeks with antibiotics, whereas prosthetic-valve endocarditis requires 6 weeks of therapy. The cure rates for HACEK prosthetic-valve endocarditis appear to be high. Unlike prosthetic-valve endocarditis caused by other gram-negative organisms, HACEK endocarditis is often cured with antibiotic treatment alone—i.e., without surgical intervention.
Table 146-1 Treatment of Endocarditis Caused by HACEK Group Organismsa
| Save Table
Table 146-1 Treatment of Endocarditis Caused by HACEK Group Organismsa
|Organism||Initial Therapy||Alternative Agents||Comments|
|Haemophilus species, Aggregatibacter actinomycetemcomitans||Ceftriaxone (2 g/d)||Ampicillin/sulbactam (3 g of ampicillin q6h) or fluoroquinolonesb||Ampicillin ± ...|
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