Gonzalez, Joaquin Bernardo MD*; Woc-Colburn, Laila MD*; Schreckenberger, Paul C. PhD†; Malow, James B. MD*
*Department of Medicine, Illinois Masonic Medical Center, Department of Medicine, Chicago; and †Department of Pathology, Loyola University Medical Center, Maywood, IL 60657.
Address correspondence and reprint requests to Joaquin Bernardo Gonzalez, MD, Advocate Illinois Masonic Medical Center, Chicago, IL. E-mail: firstname.lastname@example.org.
A 29-year-old man was admitted to Advocate Illinois Masonic Medical Center on August 29, 2003, with a 1-month duration of increasing shortness of breath and left-sided chest pain. He had a documented history of bicuspid aortic valve (BAV). Two months before admission, he presented to another hospital with similar complaints associated with fever and chills. The workup at that time showed electrocardiographic changes of diffuse ST segment elevation and a transthoracic echocardiogram with a small pericardial effusion and a BAV with no vegetations. The diagnosis was viral myopericarditis, which was treated with nonsteroidal anti-inflammatory drugs. His symptoms did not show the expected improvement; hence, he was reevaluated with a follow-up echocardiogram that was essentially unchanged. Two weeks before admission, his shortness of breath increased and became associated with orthopnea, retrosternal chest pain, decreased exercise tolerance, paroxysmal nocturnal dyspnea, and fatigue. He denied weight loss, lower extremity swelling, or palpitations. There was no history of intravenous drug abuse, no recent dental work, no surgery, and no sick contacts. Thus, the patient was admitted for further evaluation.
On admission, his vital signs were as follows: blood pressure, 125/35 mmHg; heart rate, 93 bpm; respiratory rate, 24 rpm; and temperature, 37°C. On physical examination, the patient was found to be alert, diaphoretic, and in mild respiratory distress. On examination of the mouth, neither dental caries nor periodontal lesions were seen. Neck examination showed no jugular vein distention. Chest examination revealed rales in the lower one third of the lung fields bilaterally. On cardiac examination, the patient was in a normal sinus rhythm, S1 to S2 were normal, and there was no S3; a 2/6 systolic murmur was evident along the upper right sternal border along with a 2/4 diastolic murmur along the left lower sternal border. The abdominal examination was normal. No skin lesions were seen. The neurological examination was entirely within normal limits.
Laboratory evaluation showed an O2 saturation of 97% on room air, mild leukocytosis (11,300 K/μL, 72% neutrophils, 19% lymphocytes, and no bands), a normocytic normochromic anemia, and normal renal and hepatic functions. A transthoracic echocardiogram revealed dilated and hyperdynamic left-sided chambers and a disrupted aortic valve with thickening and possible vegetations on the leaflets. Doppler evaluation was consistent with severe aortic regurgitation (Fig. 1). Subsequently, a transesophageal echocardiogram showed a markedly abnormal aortic valve with vegetations and partial disruption of both cusps. The intravalvular fibrosa was found to be intact, but partial dehiscence of the superior wall of the aorta was present (Fig. 2). The patient had blood cultures drawn and was started on intravenous vancomycin, gentamicin, and ampicillin. Cardiovascular surgery evaluated the patient and planned an urgent aortic valve replacement (AVR).
Twelve hours after admission, the patient developed the acute onset of slurred speech and numbness and tingling of his tongue and left arm. Neurological examination revealed a left facial droop. Magnetic resonance imaging of the brain showed 2 acute infarcts involving the right frontal parietal lobe white matter and the right parietal occipital cortex; there was no evidence of hemorrhage. The lesions were considered embolic. Magnetic resonance angiography of the brain showed normal vasculature; no aneurysms were visualized.
On hospital day 5, the patient underwent AVR surgery. The findings at surgery consisted of a large aortic vegetation with a perivalvular abscess that was drained and closed. The valve was replaced with an Omnicarbon mechanical valve. The cultures performed on the valve that was removed ultimately showed no growth. However, blood cultures drawn previously were positive in 1 of 2 bottles. The isolate initially grew better anaerobically than aerobically and stained partially gram positive. Gas liquid chromatographic analysis of products from glucose metabolism showed that major amounts of lactic and succinic acids were formed with a minor amount of acetic acid. This led to the consideration of Actinomyces or Eubacterium as possible taxa. Further testing revealed that the organism was asaccharolytic, indole positive, and nitrate negative. The Gram stain showed short rods with terminal swellings and some gram-positive staining. Because of the combination of the absence of butyric acid formation and indole positivity, we considered the possibility of Eubacterium tenue. Because E. tenue had not previously been reported to cause endocarditis, the isolate was referred to the ARUP Laboratories, Inc (Salt Lake City, Utah) for partial 16S ribosomal RNA gene sequencing that resulted in an identification of Cardiobacterium valvarum (98.6% similarity to MicroSeq database and 98% to GenBank). A full description of the sequencing protocol is published elsewhere.1
The patient was discharged with the following intravenous antibiotics: ceftriaxone (2 g IV daily for a total of 5 weeks) and vancomycin (1 g IV every 12 hours for a total of 2 weeks). The patient tolerated the treatment well. Three-year follow-up finds him functioning normally, with no complications from the disease and/or the treatment.
REVIEW OF LITERATURE
The BAV is the most common congenital cardiac malformation with an incidence of 1% to 2% in the general population.2 The pathogenesis of this congenital aortic valve malformation is unknown. The association of BAV with aortic stenosis, aortic regurgitation, and infective endocarditis has been known for over a century.3
Infective endocarditis due to fastidious microorganisms is common. Some of these fastidious organisms include the following group of bacteria: Haemophilus parainfluenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium species, Eikenella corrodens, and Kingella kingae (HACEK) that account for 3% of the cases.4 Other risk factors for developing infection by the HACEK group include previous dental procedures, young and middle-aged adults, previous underlying heart disease, and preference for the mitral valve. Valvular vegetations detected by echocardiography are thought to be characteristically large, perhaps the result of delayed diagnosis.4
The genus Cardiobacterium was established in 1964 as a fastidious pleomorphic gram-negative bacteria isolated from patients with endocarditis.5 Members of this genus are known to produce rods of varying length with rounded or teardrop-shaped ends. They are described as gram negative, but retention of crystal violet may occur in the swollen ends or central portions of the cell. They are facultative anaerobes that grow poorly in air unless the humidity is increased; they grow optimally in atmospheres containing 3% to 5% CO2.5 Cardiobacterium species are part of the normal oral flora, and prior dental procedures or a history of oral infections was found in 44% of patients with endocarditis.6,7 There are 76 reported cases of endocarditis caused by Cardiobacterium hominis.6 As opposed to the rest of the HACEK organisms, C. hominis infects the aortic valve more frequently than the other valves.6 The mortality associated with this organism is approximately 13%, with 30% of patients requiring valve replacement.6
Compared with C. hominis, there have only been 3 previously reported cases of endocarditis due to C. valvarum.7-40 Cardiobacterium valvarum is a newly described bacterial species from this genus. It was first isolated in 2001 by Han et al7 from a patient with endocarditis. The name is derived from its assumed preference for cardiac valves.7 The organism is a fastidious pleomorphic gram-negative bacillus, presumably of human origin. It can be found in the oral cavity and may be associated with periodontal disease.10 The fact that it is infrequent and fastidious could explain why the organism has been underrecognized for so long. We believe that some cases of endocarditis caused by C. hominis described in the past11,12 could have been erroneously identified and, in reality, were C. valvarum. This issue is clinically important because C. valvarum could represent a more destructive microorganism, producing a higher rate of complications. However, some of the complications may also be related to the indolent nature of the infection combined with the organism's destructive tendencies.
The characteristics of our case and of the 3 other cases of C. valvarum endocarditis (Table 1) already in the literature include the following: mean age of presentation of 40 years; all of the cases were male subjects, and all had a history of BAV; and the presentation in all was insidious. Two of the cases had prior dental procedures and presented with fever. All required AVR. The reasons for valve replacement included either heart failure or signs of a perivalvular abscess on noninvasive diagnostic testing. Two of the 4 cases were complicated by neurological events: one of them by a subarachnoid hemorrhage secondary to a mycotic aneurysm and the other by multiple embolic ischemic strokes. All patients were treated with β-lactam antibiotics; 3 received therapy for 4 to 6 weeks, whereas the duration for the fourth was not defined.
In summary, patients presenting with clinical findings consistent with endocarditis of insidious onset, with a history of BAV, should have C. valvarum considered strongly in the differential diagnosis as a possible etiologic agent. The antibiotic regimen would be geared empirically for the treatment of endocarditis with an extended spectrum β-lactam and vancomycin until final identification and susceptibilities are available. Early diagnosis and surgical consultation should be considered to minimize the risk of complications based on the destructive nature of this microbe.
The authors thank Dr John N. Sheagren for helpful advice and editorial assistance.
1. Petti CA, Polage CR, Schreckenberger P. The role of 16S rRNA gene sequencing in identification of microorganisms misidentified by conventional methods. J Clin Microbiol. 2005;43:6123-6125.
2. Fedak PW, Verma S, David TE, et al. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation. 2002;106:900-904.
3. Ward C. Clinical significance of the bicuspid aortic valve. Heart. 2000;83:81-85.
4. Berbari EF, Cockerill FR, Steckelberg JM. Infective endocarditis due to unusual or fastidious microorganisms. Mayo Clin Proc. 1997;72(6):532-542.
5. Slotnick IJ, Dougherty M. Further characterization of an unclassified group of bacteria causing endocarditis in man: Cardiobacterium hominis gen. et sp. n. Antonie Van Leeuwenhoek. 1964;30:261-272.
6. Brouqui P, Raoult D. Endocarditis due to rare and fastidious bacteria. Clin Microbiol Rev. 2001;14(1):177-207.
7. Han XY, Meltzer MC, Woods JT, et al. Endocarditis with ruptured cerebral aneurysm caused by Cardiobacterium valvarum sp. nov. J Clin Microbiol. 2004;4:1590-1595.
8. Hoover SE, Fischer SH, Shaffrer R, et al. Endocarditis due to a novel Cardiobacterium species. Ann Intern Med. 2005;142:229-230.
9. Bothelo E, Gouriet F, Fournier PE, et al. Endocarditis caused by Cardiobacterium valvarum. J Clin Microbiol. 2006;44:657-658.
10. Han XY, Falsen E. Characterization of oral strains of Cardiobacterium valvarum and emended description of the organism. J Clin Microbiol. 2005;43:2370-2374.
11. Currie PF, Codispoti M, Mankad PS, et al. Late aortic homograft valve endocarditis caused by Cardiobacterium hominis: a case report and review of the literature. Heart. 2000;83:579-581.
12. Lamas CC, Eykyn SJ. Bicuspid aortic valve-a silent danger: analysis of 50 cases of infective endocarditis. Clin Infect Dis. 2000;30:336-341.
© 2007 Lippincott Williams & Wilkins, Inc.