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HACEK organisms are a group of fastidious, slow-growing, gram-negative bacteria whose growth requires an atmosphere of carbon dioxide. These organisms do not grow on media routinely used for enteric bacteria (e.g., MacConkey agar). Species belonging to this group include several Haemophilus species, Aggregatibacter (formerly Actinobacillus) species, Cardiobacterium species, 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. 123). HACEK bacteremia is strongly predictive of underlying infective endocarditis (overall positive predictive value, 60%). However, this association varies significantly by organism. For example, in one study, infective endocarditis was diagnosed in 100% of patients with Aggregatibacter actinomycetemcomitans bacteremia but in no patients with Eikenella bacteremia.

In large series, 0.8–6% of cases of infective endocarditis are attributable to HACEK organisms, most often Aggregatibacter species, Haemophilus species, and Cardiobacterium hominis. Invasive infection typically occurs in patients with a history of cardiac valvular disease or prosthetic valves, often in the setting of a recent dental procedure or nasopharyngeal infection. The aortic and mitral valves are most commonly affected. The clinical course of HACEK endocarditis tends to be subacute, particularly with Aggregatibacter or Cardiobacterium. However, K. kingae endocarditis may have a more aggressive presentation. Compared with non-HACEK endocarditis, HACEK endocarditis occurs in younger patients and is more frequently associated with embolic, vascular, and immunologic manifestations. Systemic 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. Aggregatibacter and Haemophilus species cause mitral valve vegetations most often; Cardiobacterium is associated with aortic valve vegetations.

The microbiology laboratory should be alerted when a HACEK organism is being considered. Most cultures that ultimately yield a HACEK organism become positive within the first week, especially with improved culture systems such as BACTEC. Studies have not shown that prolonged incubation increases laboratory recovery of clinically significant HACEK isolates. Polymerase chain reaction (PCR) techniques, such as gene amplification of 16S rRNA, can facilitate the diagnosis of HACEK infection of blood or cardiac valves. Other tools, such as matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry performed directly on agar colonies, can increase the accuracy and speed of diagnosis of HACEK infections.

Because of HACEK organisms’ slow growth, antimicrobial susceptibility testing may be difficult, and β-lactamase production may not be detected. Resistance is most commonly noted in Haemophilus and Aggregatibacter species. Etest methodology may increase the accuracy of susceptibility testing. In recent studies, ceftriaxone and levofloxacin have been active against all isolates. The overall prognosis in both native-valve and prosthetic-valve HACEK endocarditis is excellent and is significantly better than that in endocarditis caused by non-HACEK pathogens.

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