Cardiobacterium hominis Endocarditis With Cerebral Mycotic Aneurysm Jose
\s=b\ Cardiobacterium hominis, a recently recognized Gram-negative pathogen, was recovered in blood cultures from
a
65-
year-old man with indolent endocarditis of previously normal heart valves. Despite the low virulence of the organism, major cardiac damage required valvular replacement, and there were multiple cerebral emboli with development of a mycotic aneurysm. After bacteriological cure, he died of a ruptured aneurysm. (Arch Neurol 32:638-639, 1975) hominis is a bac¬ low viru¬ in 1962.1·2 Despite the high incidence of C hominis in an upper-respiratory tract and stool sur¬ vey,3·4 by 1968, there were only 14 iso¬ lations of this agent in human dis¬ ease,5 and only eight case records have been published.1-5"7 We empha¬ size the potential of this little-known pathogen for tissue destruction, and describe endocarditis simultaneously
Cardi obacteriuapparently m lence, recognized terium of
affecting previously normal aortic and mitral valves, complicated by a cerebral mycotic aneurysm. REPORT OF A CASE A 65-year-old man had experienced the abrupt onset of aphasia with no substan¬ tial motor deficit. Hepatosplenomegaly and a normochromic, normocytic anemia were noted at that time. The patient had no pre¬ vious history of rheumatic fever. Three months later, he was readmitted to the In¬ stitute of Rehabilitation Medicine. He was pale, had moderate expressive aphasia and had a 38.44 C (101.2 P) temperature read¬ ing. The pulse rate was 100 beats per min¬ ute, respirations were 22 per minute and the blood pressure was 160/70 mm Hg. A grade 2/6 diastolic blowing heart murmur was heard at both the second and third left costal interspaces, and a grade 3/6 midsystolic ejection murmur was heard at the
Accepted for publication Nov 4, 1974. From the departments of neurology, pathology, and medicine, New York University School of Medicine.
Reprint requests to the University of Arizona, Arizona Medical Center, 1501 N Campbell Ave, Tucson, AZ 85724 (Dr. Laguna).
Laguna, MD; Bennett M. Derby, MD; Randolph Chase, MD
fourth and fifth left interspaces in the midclavicular line. Hepatosplenomegaly was present. There were no clubbing, splinter hemorrhages, or petechiae. There was a tender erythematous lesion of the skin over the right internal malleolus, and the patient had a mild, hypochromic ane¬ mia. The white blood cell (WBC) count was 8,600/cu mm with a normal differential cell count. Liver function tests and blood urea nitrogen (BUN) levels were normal. Twelve blood samples for cultures were drawn while the patient was receiving erythromycin; all were negative. On dis¬ continuation of the antibiotic therapy, three blood cultures showed positive re¬ sults for Gram-negative rods. The patient was transferred to the University Hospital where intravenously administered penicil¬ lin G sodium and intramuscularly adminis¬ tered streptomycin therapy was begun. Later, we substituted ampicillin sodium, 16 gm/day, when sensitivities became avail¬ able. The following day, the patient devel¬ oped acute respiratory distress, and he was treated for congestive heart failure. The pulse pressure widened (130/40-0) with es¬ sentially unchanged murmurs, he devel¬ oped angina, and he had episodes of agi¬ tated disorientation requiring sedation. Fifteen days later, he became unrespon¬ sive and developed a left hemiparesis. Cerebrospinal fluid (CSF) was bloody and was xanthochromic after centrifugation, with a pressure of 180 mm H20. A right ca¬ rotid angiogram showed a retrosylvian avascular mass effect, consistent with ei¬ ther hemorrhage or swelling. No aneurysm
apparent. Hemiparesis improved over hours, and the patient became respon¬
was
48 sive. Because of intractable cardiac fail¬ ure, he underwent open heart surgery four days later. A 6-mm diameter perforation
otherwise normal mitral valve was repaired. The aortic valve was disrupted along the free edge of the right coronary cusp, with a 4-mm wide edge hanging freely into the ventricular outflow tract, and was replaced with a No. 2 McGovern valve. The excised cusps were thickened and had bright yellowish areas. Microscop¬ ical examination showed fibrosis, neovascularization, myxoid change, calcifica¬ tion, and chronic inflammation with giant cells. Tissue Gram stain showed clusters of bacilli, which stained variably, but orgaof
an
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 05/24/2015
nisms did not grow in cultures of the valve. A rash developed and, after three weeks of therapy, ampicillin was discontinued. Postoperatively, clindamycin was given in¬ travenously each day for 3Vè weeks. One week after surgery, the patient became lethargic and confused with the onset of persistent left hemiparesis. Cerebrospinal fluid was xanthochromic and showed nor¬ mal pressure. Cortical blindness was sus¬ pected. Administration of warfarin sodium was begun; two weeks later, he developed left hemiplegia involving the face. Al¬ though awake, he did not speak. His pupils and brain stem reflexes were normal. War¬ farin therapy was discontinued and vita¬ min was administered. A lumbar punc¬ ture revealed grossly bloody CSF under a pressure of 470 mm of H20. Subsequently, he showed a decreased level of conscious¬ ness, lying with his eyes shut, and with minimal spontaneous activity on the right side. A second right carotid angiogram showed a right to left shift of the anterior cerebral arteries, an aneurysm in a distal posterior parietal branch of the right middle cerebral artery, and a large avascular retrosylvian mass. The patient died one month later. Identification of the organism grown in blood culture was C hominis. At autopsy, there was no evidence of rheumatic heart disease or recurrent infec¬ tion. The brain weighed 1,500 gm. The right hemisphere showed tentorial notch¬ ing of the parahippocampal gyrus without midbrain compression. Over a distal seg¬ ment of a temporoparietal branch of the
right middle cerebral artery, a subpial an¬ eurysm was present. The adjacent gyri showed tan discoloration and softening.
Serial coronal sections revealed the aneu¬ rysm, cortical infarction, and aging hemor¬
rhage extending into central white matter, 7 cm rostrocaudally and 4 cm in largest transverse diameter (Figure). The left su¬ perior temporal gyrus showed an old cavitated infarct extending posteriorly into the occipital lobe. Microscopically, the an¬ eurysm showed a collagenized wall and an organized thrombosed lumen. Remnants of an internal elastic lamina were present. There was no evidence of active infection. COMMENT There
was no
apparent
source
for
aortic valvular destruction occurred in valves uninvolved with previous heart disease. Pathological findings at the time of surgery on the aortic cusps were consistent with partially healed endocarditis. A second em¬ bolus was lodged in a distal branch of the right middle cerebral artery. De¬ struction of the internal elastic lamina at the level of the occlusion suggests that the embolus was septic, and responsible for a clinical right hemisphere syndrome, probably due to hemorrhagic infarction. Twentyfive days later, a definite right intracerebral hemorrhage occurred be¬ cause of a mycotic aneurysm in the
must be approached with caution, since apparent or silent cerebral le¬ sions may be complicated by second¬ ary hemorrhage. In the 1940s, there was a trend to use heparin or dicumarol for anticoagulation therapy, as an adjunct to penicillin G sodium ther¬ apy, in an attempt to aid antibiotic penetration of the vegetation in en¬ docarditis. This attempt was short¬ lived, due to the high incidence of le¬ thal cerebral hemorrhage.1011 Once a cerebral wall has been struc¬ turally damaged by bacterial infec¬ tion, rupture with bleeding may occur subsequently, without regard to the effectiveness of antimicrobial agents. The effects of the right cerebral lesion were superimposed on the deficit of an earlier left cerebral infarction. Thus, hemispheric tissue loss was bi¬ lateral and severe, producing a pro¬ found pseudobulbar state with mut¬ ism, and blindness due to bilateral in¬ terruption of calcarine pathways. Al¬ though the endocarditis was cured and heart failure had been reversed, death occurred because of irreversible brain damage. The eight cases of C hominis endo¬ carditis reported earlier involved five men and three women between the ages of 33 and 65 years. In six cases, there were preexisting cardiac le¬ sions, but in two patients,1·6 there was no evidence of previous heart disease. In one patient, a femoral artery mycotic aneurysm developed after antibiotic therapy.5 This patient had also experienced a subarachnoid hem¬ orrhage a few months earlier, when splenomegaly was first noted. Al¬ though cerebral arteriography showed no definite abnormality, it is probable that bacterial cerebral arteritis was
same
present.
Brain
through right occipital lobe
show¬
ing hemorrhage, ruptured mycotic aneu¬ rysm (single arrowhead), distal thrombosis
of vessel (double arrowheads), and old cortical infarction (small arrowheads).
the endocarditis that appeared as em¬ bolie left cerebral infarction. Spleno¬ megaly and the anemia of chronic infection were already established. Mitral perforation and progressive
vessel. This sequence of two
separate clinical episodes involving
the same cerebral hemisphere, the first due to embolie lodgement and the second due to mycotic aneurysm hemorrhage four weeks later, was also recorded by Roach and Drake.8 In another case, results of arteriography at the time of hemorrhage were nor¬ mal, but an arteriogram two months later showed a mycotic aneurysm.9 The routine introduction of anticoagulation agents after open heart surgery in patients with endocarditis
The causative organism is fastid¬ ious, requiring increased carbon di¬ oxide and high humidity for the development of tiny, slowly-enlarg¬
ing
colonies. Identification of the
small, Gram-negative pleomorphic
depends on a positive oxidase re¬ action, positive indole production, and on the lack of catalase production and nitrate reduction that distinguishes it from the other small Gram-negative coccobacilli such as Hemophilus, Brurod
cella, Pasteurella, and Actinoba-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 05/24/2015
cillus.2·1
Although C hominis has been iso¬ lated rarely in human disease, all recorded isolates, with the exception of one, have been from blood associ¬ ated with endocarditis, and in one case associated with newborn septi¬ cemia.1 One strain was cultured from a CSF sample, but no details were available.5 Previous isolates,1·5·7 as well as the C hominis organism grown from our patient, were sensi¬ tive to the entire range of antibiotics. Antibiotic therapy in all previous pa¬ tients has centered on high-dose peni¬ cillin G sodium administered intrave¬ nously in amounts ranging between 10 and 50 million units each day, com¬ bined with 2 gm of intramuscularly administered streptomycin, given for four to six weeks. The addition of streptomycin has been suggested for L-phase variant.12 The eight cases re¬ ported earlier and the present case were all bacteriologically cured. References 1. Tucker DH, Slotnick IJ, King EO, et al: Endocarditis caused by a Pasteurella-like organism: Report of four cases. N Engl J Med 267:913-916, 1962. 2. 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 30:261-272, 1964. 3. Slotnick IJ, Mertz JA, Dougherty M: Fluorescent antibody detection of human occurrence of an unclassified bacterial group causing endocarditis. J Infect Dis 114:503-505, 1964. 4. Slotnick IJ: Cardiobacterium hominis in genitourinary specimens. J Bacteriol 95:1174, 1968. 5. Perdue GD Jr, Dorney ER, Ferrier F: Embolomycotic aneurysm associated with bacterial endocarditis due to Cardiobacterium hominis. Am Surg 34:901-904, 1968. 6. Snyder AI, Ellner PD: Cardiobacterium hominis endocarditis. NY State J Med 69:704\x=req-\ 705, 1969. 7. Midgley J, Lapage SP, Jenkins BAG, et al: Cardiobacterium hominis endocarditis. J Med Microbiol 3:91-98, 1970. 8. Roach MR, Drake CG: Ruptured cerebral aneurysms caused by microorganisms. N Engl J Med 273:240-244, 1965. 9. Cantu RC, LeMay M, Wilkinson HA: The importance of repeated angiography in the treatment of mycotic-embolic intracranial aneurysms. J Neurosurg 25:189-193, 1966. 10. Cohen SM: Massive cerebral hemorrhage following heparin therapy in subacute bacterial endocarditis: Report of two cases with a review of the literature. J Mt Sinai Hosp 16:214-230, 1949. 11. Duff IF, Shull WH: Fatal hemorrhage in Dicumarol poisoning: With report of necropsy. JAMA 139:762-766, 1949. 12. Chase RM: Infective endocarditis today. Med Clin North Am 57:1383-1393, 1973.
\s=b\ Cardiobacterium hominis, a recently recognized Gram-negative pathogen, was recovered in blood cultures from
a
65-
year-old man with indolent endocarditis of previously normal heart valves. Despite the low virulence of the organism, major cardiac damage required valvular replacement, and there were multiple cerebral emboli with development of a mycotic aneurysm. After bacteriological cure, he died of a ruptured aneurysm. (Arch Neurol 32:638-639, 1975) hominis is a bac¬ low viru¬ in 1962.1·2 Despite the high incidence of C hominis in an upper-respiratory tract and stool sur¬ vey,3·4 by 1968, there were only 14 iso¬ lations of this agent in human dis¬ ease,5 and only eight case records have been published.1-5"7 We empha¬ size the potential of this little-known pathogen for tissue destruction, and describe endocarditis simultaneously
Cardi obacteriuapparently m lence, recognized terium of
affecting previously normal aortic and mitral valves, complicated by a cerebral mycotic aneurysm. REPORT OF A CASE A 65-year-old man had experienced the abrupt onset of aphasia with no substan¬ tial motor deficit. Hepatosplenomegaly and a normochromic, normocytic anemia were noted at that time. The patient had no pre¬ vious history of rheumatic fever. Three months later, he was readmitted to the In¬ stitute of Rehabilitation Medicine. He was pale, had moderate expressive aphasia and had a 38.44 C (101.2 P) temperature read¬ ing. The pulse rate was 100 beats per min¬ ute, respirations were 22 per minute and the blood pressure was 160/70 mm Hg. A grade 2/6 diastolic blowing heart murmur was heard at both the second and third left costal interspaces, and a grade 3/6 midsystolic ejection murmur was heard at the
Accepted for publication Nov 4, 1974. From the departments of neurology, pathology, and medicine, New York University School of Medicine.
Reprint requests to the University of Arizona, Arizona Medical Center, 1501 N Campbell Ave, Tucson, AZ 85724 (Dr. Laguna).
Laguna, MD; Bennett M. Derby, MD; Randolph Chase, MD
fourth and fifth left interspaces in the midclavicular line. Hepatosplenomegaly was present. There were no clubbing, splinter hemorrhages, or petechiae. There was a tender erythematous lesion of the skin over the right internal malleolus, and the patient had a mild, hypochromic ane¬ mia. The white blood cell (WBC) count was 8,600/cu mm with a normal differential cell count. Liver function tests and blood urea nitrogen (BUN) levels were normal. Twelve blood samples for cultures were drawn while the patient was receiving erythromycin; all were negative. On dis¬ continuation of the antibiotic therapy, three blood cultures showed positive re¬ sults for Gram-negative rods. The patient was transferred to the University Hospital where intravenously administered penicil¬ lin G sodium and intramuscularly adminis¬ tered streptomycin therapy was begun. Later, we substituted ampicillin sodium, 16 gm/day, when sensitivities became avail¬ able. The following day, the patient devel¬ oped acute respiratory distress, and he was treated for congestive heart failure. The pulse pressure widened (130/40-0) with es¬ sentially unchanged murmurs, he devel¬ oped angina, and he had episodes of agi¬ tated disorientation requiring sedation. Fifteen days later, he became unrespon¬ sive and developed a left hemiparesis. Cerebrospinal fluid (CSF) was bloody and was xanthochromic after centrifugation, with a pressure of 180 mm H20. A right ca¬ rotid angiogram showed a retrosylvian avascular mass effect, consistent with ei¬ ther hemorrhage or swelling. No aneurysm
apparent. Hemiparesis improved over hours, and the patient became respon¬
was
48 sive. Because of intractable cardiac fail¬ ure, he underwent open heart surgery four days later. A 6-mm diameter perforation
otherwise normal mitral valve was repaired. The aortic valve was disrupted along the free edge of the right coronary cusp, with a 4-mm wide edge hanging freely into the ventricular outflow tract, and was replaced with a No. 2 McGovern valve. The excised cusps were thickened and had bright yellowish areas. Microscop¬ ical examination showed fibrosis, neovascularization, myxoid change, calcifica¬ tion, and chronic inflammation with giant cells. Tissue Gram stain showed clusters of bacilli, which stained variably, but orgaof
an
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 05/24/2015
nisms did not grow in cultures of the valve. A rash developed and, after three weeks of therapy, ampicillin was discontinued. Postoperatively, clindamycin was given in¬ travenously each day for 3Vè weeks. One week after surgery, the patient became lethargic and confused with the onset of persistent left hemiparesis. Cerebrospinal fluid was xanthochromic and showed nor¬ mal pressure. Cortical blindness was sus¬ pected. Administration of warfarin sodium was begun; two weeks later, he developed left hemiplegia involving the face. Al¬ though awake, he did not speak. His pupils and brain stem reflexes were normal. War¬ farin therapy was discontinued and vita¬ min was administered. A lumbar punc¬ ture revealed grossly bloody CSF under a pressure of 470 mm of H20. Subsequently, he showed a decreased level of conscious¬ ness, lying with his eyes shut, and with minimal spontaneous activity on the right side. A second right carotid angiogram showed a right to left shift of the anterior cerebral arteries, an aneurysm in a distal posterior parietal branch of the right middle cerebral artery, and a large avascular retrosylvian mass. The patient died one month later. Identification of the organism grown in blood culture was C hominis. At autopsy, there was no evidence of rheumatic heart disease or recurrent infec¬ tion. The brain weighed 1,500 gm. The right hemisphere showed tentorial notch¬ ing of the parahippocampal gyrus without midbrain compression. Over a distal seg¬ ment of a temporoparietal branch of the
right middle cerebral artery, a subpial an¬ eurysm was present. The adjacent gyri showed tan discoloration and softening.
Serial coronal sections revealed the aneu¬ rysm, cortical infarction, and aging hemor¬
rhage extending into central white matter, 7 cm rostrocaudally and 4 cm in largest transverse diameter (Figure). The left su¬ perior temporal gyrus showed an old cavitated infarct extending posteriorly into the occipital lobe. Microscopically, the an¬ eurysm showed a collagenized wall and an organized thrombosed lumen. Remnants of an internal elastic lamina were present. There was no evidence of active infection. COMMENT There
was no
apparent
source
for
aortic valvular destruction occurred in valves uninvolved with previous heart disease. Pathological findings at the time of surgery on the aortic cusps were consistent with partially healed endocarditis. A second em¬ bolus was lodged in a distal branch of the right middle cerebral artery. De¬ struction of the internal elastic lamina at the level of the occlusion suggests that the embolus was septic, and responsible for a clinical right hemisphere syndrome, probably due to hemorrhagic infarction. Twentyfive days later, a definite right intracerebral hemorrhage occurred be¬ cause of a mycotic aneurysm in the
must be approached with caution, since apparent or silent cerebral le¬ sions may be complicated by second¬ ary hemorrhage. In the 1940s, there was a trend to use heparin or dicumarol for anticoagulation therapy, as an adjunct to penicillin G sodium ther¬ apy, in an attempt to aid antibiotic penetration of the vegetation in en¬ docarditis. This attempt was short¬ lived, due to the high incidence of le¬ thal cerebral hemorrhage.1011 Once a cerebral wall has been struc¬ turally damaged by bacterial infec¬ tion, rupture with bleeding may occur subsequently, without regard to the effectiveness of antimicrobial agents. The effects of the right cerebral lesion were superimposed on the deficit of an earlier left cerebral infarction. Thus, hemispheric tissue loss was bi¬ lateral and severe, producing a pro¬ found pseudobulbar state with mut¬ ism, and blindness due to bilateral in¬ terruption of calcarine pathways. Al¬ though the endocarditis was cured and heart failure had been reversed, death occurred because of irreversible brain damage. The eight cases of C hominis endo¬ carditis reported earlier involved five men and three women between the ages of 33 and 65 years. In six cases, there were preexisting cardiac le¬ sions, but in two patients,1·6 there was no evidence of previous heart disease. In one patient, a femoral artery mycotic aneurysm developed after antibiotic therapy.5 This patient had also experienced a subarachnoid hem¬ orrhage a few months earlier, when splenomegaly was first noted. Al¬ though cerebral arteriography showed no definite abnormality, it is probable that bacterial cerebral arteritis was
same
present.
Brain
through right occipital lobe
show¬
ing hemorrhage, ruptured mycotic aneu¬ rysm (single arrowhead), distal thrombosis
of vessel (double arrowheads), and old cortical infarction (small arrowheads).
the endocarditis that appeared as em¬ bolie left cerebral infarction. Spleno¬ megaly and the anemia of chronic infection were already established. Mitral perforation and progressive
vessel. This sequence of two
separate clinical episodes involving
the same cerebral hemisphere, the first due to embolie lodgement and the second due to mycotic aneurysm hemorrhage four weeks later, was also recorded by Roach and Drake.8 In another case, results of arteriography at the time of hemorrhage were nor¬ mal, but an arteriogram two months later showed a mycotic aneurysm.9 The routine introduction of anticoagulation agents after open heart surgery in patients with endocarditis
The causative organism is fastid¬ ious, requiring increased carbon di¬ oxide and high humidity for the development of tiny, slowly-enlarg¬
ing
colonies. Identification of the
small, Gram-negative pleomorphic
depends on a positive oxidase re¬ action, positive indole production, and on the lack of catalase production and nitrate reduction that distinguishes it from the other small Gram-negative coccobacilli such as Hemophilus, Brurod
cella, Pasteurella, and Actinoba-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 05/24/2015
cillus.2·1
Although C hominis has been iso¬ lated rarely in human disease, all recorded isolates, with the exception of one, have been from blood associ¬ ated with endocarditis, and in one case associated with newborn septi¬ cemia.1 One strain was cultured from a CSF sample, but no details were available.5 Previous isolates,1·5·7 as well as the C hominis organism grown from our patient, were sensi¬ tive to the entire range of antibiotics. Antibiotic therapy in all previous pa¬ tients has centered on high-dose peni¬ cillin G sodium administered intrave¬ nously in amounts ranging between 10 and 50 million units each day, com¬ bined with 2 gm of intramuscularly administered streptomycin, given for four to six weeks. The addition of streptomycin has been suggested for L-phase variant.12 The eight cases re¬ ported earlier and the present case were all bacteriologically cured. References 1. Tucker DH, Slotnick IJ, King EO, et al: Endocarditis caused by a Pasteurella-like organism: Report of four cases. N Engl J Med 267:913-916, 1962. 2. 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 30:261-272, 1964. 3. Slotnick IJ, Mertz JA, Dougherty M: Fluorescent antibody detection of human occurrence of an unclassified bacterial group causing endocarditis. J Infect Dis 114:503-505, 1964. 4. Slotnick IJ: Cardiobacterium hominis in genitourinary specimens. J Bacteriol 95:1174, 1968. 5. Perdue GD Jr, Dorney ER, Ferrier F: Embolomycotic aneurysm associated with bacterial endocarditis due to Cardiobacterium hominis. Am Surg 34:901-904, 1968. 6. Snyder AI, Ellner PD: Cardiobacterium hominis endocarditis. NY State J Med 69:704\x=req-\ 705, 1969. 7. Midgley J, Lapage SP, Jenkins BAG, et al: Cardiobacterium hominis endocarditis. J Med Microbiol 3:91-98, 1970. 8. Roach MR, Drake CG: Ruptured cerebral aneurysms caused by microorganisms. N Engl J Med 273:240-244, 1965. 9. Cantu RC, LeMay M, Wilkinson HA: The importance of repeated angiography in the treatment of mycotic-embolic intracranial aneurysms. J Neurosurg 25:189-193, 1966. 10. Cohen SM: Massive cerebral hemorrhage following heparin therapy in subacute bacterial endocarditis: Report of two cases with a review of the literature. J Mt Sinai Hosp 16:214-230, 1949. 11. Duff IF, Shull WH: Fatal hemorrhage in Dicumarol poisoning: With report of necropsy. JAMA 139:762-766, 1949. 12. Chase RM: Infective endocarditis today. Med Clin North Am 57:1383-1393, 1973.
