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Cerebral Hemorrhage in Infective Endocarditis Caused by Actinobacillus actinomycetemcomitans
Cerebral Hemorrhage in Infective Endocarditis Caused by Actinobacillus actinomycetemcomitans GEN-MIN LIN, MD; KAI-MIN CHU, MD, PHD; CHUN-JUNG JUAN, MD; FENG-YEE CHANG, MD, PHD
ABSTRACT: Cerebral hemorrhage occurs rarely in endocarditis caused by Actinobacillus actinomycetemcomitans. A 51-year-old man with a prosthetic mitral valve, who had been prophylactically treated (7 years) with warfarin, presented with intermittent fever. On admission, a Levine grade II/VI systolic cardiac murmur was detected. A transthoracic echocardiogram was negative for valve vegetation. Cefepime (1 g every 8 hours) was administered intravenously. On day 4, culturing of Gram-negative bacilli from blood and a transesophageal echocardiogram revealed a small oscillating filament attached to lateral mitral prosthetic ring on the atrial
A
ctinobacillus actinomycetemcomitans, a Gramnegative bacillus, is the most common organism of the HACEK group (Haemophilus species, A actinomycetemcomitans, Cardiobacter hominis, Eikenella corrodens, and Kingella species), which accounts for a small percentage (approximately 3%) of the total cases of infective endocarditis (IE).1– 4 Characteristics of this organism include its slow growth rate and susceptibility to antimicrobial agents. Septic embolism is the major complication but cerebral hemorrhage is rare. We report a case of cerebral hemorrhage complicating IE caused by A actinomycetemcomitans. Four more cases reported previously in the English literature1– 4 are reviewed.
From the Division of Infectious Diseases and Tropical Medicine (G-ML, F-YC), Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; the Department of Internal Medicine (G-ML), Hualien Armed Forces General Hospital, Hualien, Taiwan; the Division of Cardiology (K-MC), Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; the Department of Radiology (C-JJ), Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; and the Department of Electrical Engineering (C-JJ), National Taiwan University, Taipei, Taiwan. Submitted December 15, 2006; accepted in revised form April 27, 2007. Correspondence: Dr. Feng-Yee Chang, No. 325, Sec. 2, ChengKung Rd., Neihu, Taipei 114, Taiwan (E-mail: fychang@ ndmctsgh.edu.tw). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
side. Ceftriaxone (2 g once daily) was started. Gait instability and left-side weakness developed abruptly 2 weeks later; brain magnetic resonance imaging revealed a hematoma over the right parietal-occipital lobe. Ceftriaxone was adjusted to 2 g every 12 hours. Actinobacillus actinomycetemcomitans was identified 3 weeks later. Recovery was achieved, with significant interval improvement and resolution of the cerebral lesions evident on CT. KEY INDEXING TERMS: Infective endocarditis; Cerebral hemorrhage; Actinobacillus actinomycetemcomitans; Warfarin treatment. [Am J Med Sci 2007; 334(5):389–392.]
Case Report A 51-year-old man was admitted via the outpatient department of Tri-Service General Hospital, Taipei, Taiwan; complaining of a 10-day intermittent fever accompanied by general malaise. Seven years previously, the patient had received a mechanical prosthetic mitral valve replacement due to severe mitral valve regurgitation. Since then, he had been prophylactically treated with warfarin. On admission, the patient was alert and displayed a body temperature of 38.6°C, pulse rate of 80 beats per minute, and a blood pressure of 120/70 mm Hg. A cardiovascular examination revealed an early systolic murmur of Levine grade II/VI over the apex. Other systemic examinations were normal. A leukocyte count of 15,040/L and elevated liver enzymes were noted. The international normalized ratio of prothrombin time (PT-INR) was 1.96. Urine was sterile. There were no pulmonary infiltrates on chest radiography, and an abdominal sonography was unremarkable. A transthoracic echocardiogram (TTE) showed no visible vegetation. Blood was collected for culture, and empiric therapy consisting of intravenous cefepime (1 g every 8 hours) was commenced. Three days later, blood cultures were positive for Gram-negative bacilli. A transesophageal echocardiography (TEE) disclosed an oscillating filament measuring 0.9 cm ⫻ 0.2 cm, attached to lateral mitral prosthetic ring on the atrial side (Figure 1). This prompted a shift in antibiotic therapy to a once-daily intravenous administration of 2 g of ceftriaxone. Two weeks after the start of this regimen, the patient suddenly developed an unstable gait and weakness of the left side limbs. Magnetic resonance imaging of the brain showed a late-subacute hematoma measuring 4.5 cm ⫻ 3.1 cm ⫻ 3.7 cm over the right occipital lobe (Figure 2A). In addition, T2-weighted images disclosed the presence of several small, hyperintense lesions in the bilateral cerebellar hemispheres (Figure 2B) and a tiny focal enhancing lesion of the left occipital lobe at the cortical surface. Magnetic resonance angiography did not show evidence of vascular occlusion, stenosis, aneurysm, or malformation. A repeat TTE showed no vegetation but mild mitral regurgitation. A repeat TEE was not obtained. The above findings were suggestive of septic cerebral embolism with related hemorrhage. Accordingly, the dosage of ceftriaxone
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was adjusted to 2 g twice daily. After a further 3 weeks, the blood culture isolate was identified as A actinomycetemcomitans. The disk diffusion susceptibility test of the isolate was performed according to the guidelines of the National Committee for Clinical Laboratory Standards and showed as susceptible to ampicillin, ceftriaxone, aztreonam, cefepime, gentamicin, amikacin, trimethoprim-sulfamethoxazole, ciprofloxacin, and imipenem. Serial follow-up CT showed significant interval improvement, and the patient was discharged without neurological sequelae after an 8-week course of the ceftriaxone treatment. Follow-up contrast-enhanced CT images conducted 3 months later revealed the complete resolution of the cerebral hematoma. But focal brain tissue loss and gliosis of the right parietal lobe was noted (Figure 3). The patient remained well at the 2-year follow-up.
Discussion
Figure 1. Transesophageal echocardiography reveals an oscillating filament (arrow) measuring 0.9 ⫻ 0.2 cm, attached to lateral mitral prosthetic ring on the atrial side. It is consistent with vegetation and infective endocarditis. AO, Aorta; LA, left atrium; LV, left ventricle; VEGE, vegetation.
In addition to the present case, we identified four more cases of IE with cerebral hemorrhage caused by A actinomycetemcomitans in a Medline search of the English literature1– 4 (Table 1). All patients fulfilled the modified Duke’s criteria for IE.5 The mean age was 50 years (range, 37 to 67 years). All patients had undergone at least 1 mechanical prosthetic valve replacement because of rheumatic heart disease. Warfarin was prescribed for 3 patients. TTE
Figure 2. Axial T1-weighted image (A), fluid-attenuated inversion recovery image (B), and postcontrast T1-weighted image (C) at the level of the lateral ventricles show a late subacute hematoma of the right parietooccipital lobe. The hematoma appears hyperintense on both T1-weighted images and FLAIR images and shows a fluffy enhancing rim after intravenous injection of gadolinium. A discrete lacunar infarction of the posterior lateral border of the left cerebellar hemisphere appears hyperintense in the diffusion-weighted image (D). The discreteness of these lesions is consistent with an embolism.
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Figure 3. Follow-up contrastenhanced CT images show focal brain tissue loss and gliosis of the right parietal lobe as a consequence of prior hemorrhage.
showed no evidence of IE for 4 patients. TEE was done only in the present case (case 5) and revealed a small vegetation on the prosthetic mitral ring. Gram-negative bacteria, subsequently identified as A actinomycetemcomitans, could be detected by Gram stain from blood culture, with a mean growth time of 4.4 days (1 to 7 days). Initially prescribed antibiotics showed in vitro activity to each identified A actinomycetemcomitans. Except for case 2, the onset of a cerebrovascular accident developed after antibiotic treatment; the mean time for onset was 16 days (range, 7 to 35 days). Intracerebral hemorrhage was diagnosed by au-
topsy in case 1, cranial CT scan in cases 2, 3, and 4, and MRI in case 5. Early detection of vegetation to fulfill the criteria for IE, pending the results of microbiological examination, is important, especially in slow growing pathogens such as those that comprise the HACEK group. Since cerebral septic embolism with hemorrhage is not related to the presence of vegetation in TTE,6 and since TEE is more sensitive and specific than TTE in revealing infective vegetations in patients with a prosthetic valve,7 a decision to perform TEE in patients with a high clinical suspicion of IE should be made.
Table 1. Cerebral Hemorrhage in Endocarditis Caused by Actinobacillus actinomycetemcomitans
Patient Ref (year)
Age (y)/Sex
Predisposing Factor for IE
[1] (1979)
37/M
[2] (1984)
47/F
[3] (1989)
67/F
[4] (1994)
48/M
[P] (2003)
51/M
Star-Edwards prosthetic mitral valve, dental abscess Mechanical prosthetic aortic and mitral valves Porcine bioprosthetic mitral, tricuspid and aortic valves Saint-Judeprosthetic aortic and mitral valves, dental procedure Carbomedics prosthetic mitral valve
Vegetation
Sites of Cerebral Day of Hemorrhage (day Positive Blood of onset after Cultures (sets) treatment)
Other Sites of Emboli
Antibiotics (duration)
Renal
Pen and Gm (5 weeks)
Died
Ceftri (7 weeks)
Cured
Outcome
Autopsy: 2 small vegetations on prosthetic valve ring Negative by TTE
7 (5/6)
Cerebral (35)
4 (NA)
Right frontalparietal lobe (0)
—
Negative by TTE
7 (9/9)
Occipital lobe (7)
Spleen
Negative by TTE
1 (3/7)
Left rolandic region (7)
—
Ceftri (7 weeks)
Negative by TTE; TEE: small vegetation on prosthetic valve ring
3 (3/3)
Right parietaloccipital lobe (14)
—
Cefep, Ceftri Cured (6 weeks)
Cefep, Ceftri Cured (6 weeks) Neurological deficits
Pen indicates penicillin; Gm, gentamicin; Ceftri, ceftriaxone; Cefep, cefepime; NA, not available; TTE, transthoracic echocardiography; TEE, transesophageal echocardiography; P, present.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
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Mechanisms of cerebral hemorrhage in IE include mycotic aneurysm, septic erosion of the arterial wall with rupture, and hemorrhagic transformation of ischemic infarcts.8,9 Other associated factors with cerebral hemorrhage in IE are anticoagulation therapy,10 host factors, and microbiology factors.11 A correlation between cerebrovascular accidents and patients with mechanical prosthetic valve receiving warfarin therapy has been noted in IE caused by A actinomycetemcomitans as well as by Staphylococcus aureus.10,11 Those patients with A actinomycetemcomitans IE had a markedly better prognosis than patients with IE caused by S aureus. Indeed, 4 of the 5 documented cases of A actinomycetemcomitans IE were resolved through the use of antibiotics. This no doubt reflects the high antibiotic susceptibility of A actinomycetemcomitans; no -lactamase production has yet been detected.12 However, cerebral septic embolism with hemorrhage still can occur when antibiotic coverage is adequate. In that regard, the drug interaction of ceftriaxone with warfarin has not been reported. In conclusion, patients with prosthetic valve endocarditis caused by A actinomycetemcomitans receiving warfarin prophylaxis may be at risk to develop cerebral hemorrhage. Yet, with a suitable antibiotic treatment regimen, their prognosis is good. References 1. Reider J, Wheat J. Endocarditis caused by Actinobacillus actinomycetemcomitans. South Med J 1979;72:1219–20.
392
2. El Khizzi NN, Kasab SA, Osoba AO. HACEK group endocarditis at the Riyadh Armed Forces Hospital. J Infect 1997; 34:69–74. 3. Hamori PJ, Slama TG. Actinobacillus prosthetic valve endocarditis. Am Heart J 1989;118:853–4. 4. Paturel L, Casalta JP, Habib G, et al. Actinobacillus actinomycetemcomitans endocarditis: Clin Microbiol Infect 2004;10:98–118. 5. Daniel WG, Mugge A, Grote J, et al. Comparison of transthoracic and transesophageal echocardiography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol 1993;1:210–5. 6. Kaplan AH, Weber DJ, Oddone EZ, et al. Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review. Rev Infect Dis 1989;11:46–63. 7. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994;96:200–9. 8. Hart RG, Kagan-Hallet K, Joerns SE. Mechanisms of intracranial hemorrhage in infective endocarditis. Stroke 1987;18:1048–56. 9. Kanter MC, Hart RG. Neurologic complications of infective endocarditis. Neurology 1991;41:1015–20. 10. Delahaye JP, Mann JM, Poncet JH. Cerebrovascular accidents in infective endocarditis: role of anticoagulation. Eur Heart J 1990;11:1074–8. 11. Roder BL, Wandall DA, Espersen F, et al. Neurologic manifestations in Staphylococcus aureus endocarditis: a review of 260 bacteremic cases in nondrug addicts. Am J Med 1997;102:379–86. 12. Madinier IM, Fosse TB, Hitzig C, et al. Resistance profile survey of 50 periodontal strains of Actinobacillus actinomycetemcomitans. J Periodontol 1999;70:888–92.
November 2007 Volume 334 Number 5
ABSTRACT: Cerebral hemorrhage occurs rarely in endocarditis caused by Actinobacillus actinomycetemcomitans. A 51-year-old man with a prosthetic mitral valve, who had been prophylactically treated (7 years) with warfarin, presented with intermittent fever. On admission, a Levine grade II/VI systolic cardiac murmur was detected. A transthoracic echocardiogram was negative for valve vegetation. Cefepime (1 g every 8 hours) was administered intravenously. On day 4, culturing of Gram-negative bacilli from blood and a transesophageal echocardiogram revealed a small oscillating filament attached to lateral mitral prosthetic ring on the atrial
A
ctinobacillus actinomycetemcomitans, a Gramnegative bacillus, is the most common organism of the HACEK group (Haemophilus species, A actinomycetemcomitans, Cardiobacter hominis, Eikenella corrodens, and Kingella species), which accounts for a small percentage (approximately 3%) of the total cases of infective endocarditis (IE).1– 4 Characteristics of this organism include its slow growth rate and susceptibility to antimicrobial agents. Septic embolism is the major complication but cerebral hemorrhage is rare. We report a case of cerebral hemorrhage complicating IE caused by A actinomycetemcomitans. Four more cases reported previously in the English literature1– 4 are reviewed.
From the Division of Infectious Diseases and Tropical Medicine (G-ML, F-YC), Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; the Department of Internal Medicine (G-ML), Hualien Armed Forces General Hospital, Hualien, Taiwan; the Division of Cardiology (K-MC), Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; the Department of Radiology (C-JJ), Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; and the Department of Electrical Engineering (C-JJ), National Taiwan University, Taipei, Taiwan. Submitted December 15, 2006; accepted in revised form April 27, 2007. Correspondence: Dr. Feng-Yee Chang, No. 325, Sec. 2, ChengKung Rd., Neihu, Taipei 114, Taiwan (E-mail: fychang@ ndmctsgh.edu.tw). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
side. Ceftriaxone (2 g once daily) was started. Gait instability and left-side weakness developed abruptly 2 weeks later; brain magnetic resonance imaging revealed a hematoma over the right parietal-occipital lobe. Ceftriaxone was adjusted to 2 g every 12 hours. Actinobacillus actinomycetemcomitans was identified 3 weeks later. Recovery was achieved, with significant interval improvement and resolution of the cerebral lesions evident on CT. KEY INDEXING TERMS: Infective endocarditis; Cerebral hemorrhage; Actinobacillus actinomycetemcomitans; Warfarin treatment. [Am J Med Sci 2007; 334(5):389–392.]
Case Report A 51-year-old man was admitted via the outpatient department of Tri-Service General Hospital, Taipei, Taiwan; complaining of a 10-day intermittent fever accompanied by general malaise. Seven years previously, the patient had received a mechanical prosthetic mitral valve replacement due to severe mitral valve regurgitation. Since then, he had been prophylactically treated with warfarin. On admission, the patient was alert and displayed a body temperature of 38.6°C, pulse rate of 80 beats per minute, and a blood pressure of 120/70 mm Hg. A cardiovascular examination revealed an early systolic murmur of Levine grade II/VI over the apex. Other systemic examinations were normal. A leukocyte count of 15,040/L and elevated liver enzymes were noted. The international normalized ratio of prothrombin time (PT-INR) was 1.96. Urine was sterile. There were no pulmonary infiltrates on chest radiography, and an abdominal sonography was unremarkable. A transthoracic echocardiogram (TTE) showed no visible vegetation. Blood was collected for culture, and empiric therapy consisting of intravenous cefepime (1 g every 8 hours) was commenced. Three days later, blood cultures were positive for Gram-negative bacilli. A transesophageal echocardiography (TEE) disclosed an oscillating filament measuring 0.9 cm ⫻ 0.2 cm, attached to lateral mitral prosthetic ring on the atrial side (Figure 1). This prompted a shift in antibiotic therapy to a once-daily intravenous administration of 2 g of ceftriaxone. Two weeks after the start of this regimen, the patient suddenly developed an unstable gait and weakness of the left side limbs. Magnetic resonance imaging of the brain showed a late-subacute hematoma measuring 4.5 cm ⫻ 3.1 cm ⫻ 3.7 cm over the right occipital lobe (Figure 2A). In addition, T2-weighted images disclosed the presence of several small, hyperintense lesions in the bilateral cerebellar hemispheres (Figure 2B) and a tiny focal enhancing lesion of the left occipital lobe at the cortical surface. Magnetic resonance angiography did not show evidence of vascular occlusion, stenosis, aneurysm, or malformation. A repeat TTE showed no vegetation but mild mitral regurgitation. A repeat TEE was not obtained. The above findings were suggestive of septic cerebral embolism with related hemorrhage. Accordingly, the dosage of ceftriaxone
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Cerebral Hemorrhage in Endocarditis
was adjusted to 2 g twice daily. After a further 3 weeks, the blood culture isolate was identified as A actinomycetemcomitans. The disk diffusion susceptibility test of the isolate was performed according to the guidelines of the National Committee for Clinical Laboratory Standards and showed as susceptible to ampicillin, ceftriaxone, aztreonam, cefepime, gentamicin, amikacin, trimethoprim-sulfamethoxazole, ciprofloxacin, and imipenem. Serial follow-up CT showed significant interval improvement, and the patient was discharged without neurological sequelae after an 8-week course of the ceftriaxone treatment. Follow-up contrast-enhanced CT images conducted 3 months later revealed the complete resolution of the cerebral hematoma. But focal brain tissue loss and gliosis of the right parietal lobe was noted (Figure 3). The patient remained well at the 2-year follow-up.
Discussion
Figure 1. Transesophageal echocardiography reveals an oscillating filament (arrow) measuring 0.9 ⫻ 0.2 cm, attached to lateral mitral prosthetic ring on the atrial side. It is consistent with vegetation and infective endocarditis. AO, Aorta; LA, left atrium; LV, left ventricle; VEGE, vegetation.
In addition to the present case, we identified four more cases of IE with cerebral hemorrhage caused by A actinomycetemcomitans in a Medline search of the English literature1– 4 (Table 1). All patients fulfilled the modified Duke’s criteria for IE.5 The mean age was 50 years (range, 37 to 67 years). All patients had undergone at least 1 mechanical prosthetic valve replacement because of rheumatic heart disease. Warfarin was prescribed for 3 patients. TTE
Figure 2. Axial T1-weighted image (A), fluid-attenuated inversion recovery image (B), and postcontrast T1-weighted image (C) at the level of the lateral ventricles show a late subacute hematoma of the right parietooccipital lobe. The hematoma appears hyperintense on both T1-weighted images and FLAIR images and shows a fluffy enhancing rim after intravenous injection of gadolinium. A discrete lacunar infarction of the posterior lateral border of the left cerebellar hemisphere appears hyperintense in the diffusion-weighted image (D). The discreteness of these lesions is consistent with an embolism.
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November 2007 Volume 334 Number 5
Lin et al
Figure 3. Follow-up contrastenhanced CT images show focal brain tissue loss and gliosis of the right parietal lobe as a consequence of prior hemorrhage.
showed no evidence of IE for 4 patients. TEE was done only in the present case (case 5) and revealed a small vegetation on the prosthetic mitral ring. Gram-negative bacteria, subsequently identified as A actinomycetemcomitans, could be detected by Gram stain from blood culture, with a mean growth time of 4.4 days (1 to 7 days). Initially prescribed antibiotics showed in vitro activity to each identified A actinomycetemcomitans. Except for case 2, the onset of a cerebrovascular accident developed after antibiotic treatment; the mean time for onset was 16 days (range, 7 to 35 days). Intracerebral hemorrhage was diagnosed by au-
topsy in case 1, cranial CT scan in cases 2, 3, and 4, and MRI in case 5. Early detection of vegetation to fulfill the criteria for IE, pending the results of microbiological examination, is important, especially in slow growing pathogens such as those that comprise the HACEK group. Since cerebral septic embolism with hemorrhage is not related to the presence of vegetation in TTE,6 and since TEE is more sensitive and specific than TTE in revealing infective vegetations in patients with a prosthetic valve,7 a decision to perform TEE in patients with a high clinical suspicion of IE should be made.
Table 1. Cerebral Hemorrhage in Endocarditis Caused by Actinobacillus actinomycetemcomitans
Patient Ref (year)
Age (y)/Sex
Predisposing Factor for IE
[1] (1979)
37/M
[2] (1984)
47/F
[3] (1989)
67/F
[4] (1994)
48/M
[P] (2003)
51/M
Star-Edwards prosthetic mitral valve, dental abscess Mechanical prosthetic aortic and mitral valves Porcine bioprosthetic mitral, tricuspid and aortic valves Saint-Judeprosthetic aortic and mitral valves, dental procedure Carbomedics prosthetic mitral valve
Vegetation
Sites of Cerebral Day of Hemorrhage (day Positive Blood of onset after Cultures (sets) treatment)
Other Sites of Emboli
Antibiotics (duration)
Renal
Pen and Gm (5 weeks)
Died
Ceftri (7 weeks)
Cured
Outcome
Autopsy: 2 small vegetations on prosthetic valve ring Negative by TTE
7 (5/6)
Cerebral (35)
4 (NA)
Right frontalparietal lobe (0)
—
Negative by TTE
7 (9/9)
Occipital lobe (7)
Spleen
Negative by TTE
1 (3/7)
Left rolandic region (7)
—
Ceftri (7 weeks)
Negative by TTE; TEE: small vegetation on prosthetic valve ring
3 (3/3)
Right parietaloccipital lobe (14)
—
Cefep, Ceftri Cured (6 weeks)
Cefep, Ceftri Cured (6 weeks) Neurological deficits
Pen indicates penicillin; Gm, gentamicin; Ceftri, ceftriaxone; Cefep, cefepime; NA, not available; TTE, transthoracic echocardiography; TEE, transesophageal echocardiography; P, present.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
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Cerebral Hemorrhage in Endocarditis
Mechanisms of cerebral hemorrhage in IE include mycotic aneurysm, septic erosion of the arterial wall with rupture, and hemorrhagic transformation of ischemic infarcts.8,9 Other associated factors with cerebral hemorrhage in IE are anticoagulation therapy,10 host factors, and microbiology factors.11 A correlation between cerebrovascular accidents and patients with mechanical prosthetic valve receiving warfarin therapy has been noted in IE caused by A actinomycetemcomitans as well as by Staphylococcus aureus.10,11 Those patients with A actinomycetemcomitans IE had a markedly better prognosis than patients with IE caused by S aureus. Indeed, 4 of the 5 documented cases of A actinomycetemcomitans IE were resolved through the use of antibiotics. This no doubt reflects the high antibiotic susceptibility of A actinomycetemcomitans; no -lactamase production has yet been detected.12 However, cerebral septic embolism with hemorrhage still can occur when antibiotic coverage is adequate. In that regard, the drug interaction of ceftriaxone with warfarin has not been reported. In conclusion, patients with prosthetic valve endocarditis caused by A actinomycetemcomitans receiving warfarin prophylaxis may be at risk to develop cerebral hemorrhage. Yet, with a suitable antibiotic treatment regimen, their prognosis is good. References 1. Reider J, Wheat J. Endocarditis caused by Actinobacillus actinomycetemcomitans. South Med J 1979;72:1219–20.
392
2. El Khizzi NN, Kasab SA, Osoba AO. HACEK group endocarditis at the Riyadh Armed Forces Hospital. J Infect 1997; 34:69–74. 3. Hamori PJ, Slama TG. Actinobacillus prosthetic valve endocarditis. Am Heart J 1989;118:853–4. 4. Paturel L, Casalta JP, Habib G, et al. Actinobacillus actinomycetemcomitans endocarditis: Clin Microbiol Infect 2004;10:98–118. 5. Daniel WG, Mugge A, Grote J, et al. Comparison of transthoracic and transesophageal echocardiography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions. Am J Cardiol 1993;1:210–5. 6. Kaplan AH, Weber DJ, Oddone EZ, et al. Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review. Rev Infect Dis 1989;11:46–63. 7. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994;96:200–9. 8. Hart RG, Kagan-Hallet K, Joerns SE. Mechanisms of intracranial hemorrhage in infective endocarditis. Stroke 1987;18:1048–56. 9. Kanter MC, Hart RG. Neurologic complications of infective endocarditis. Neurology 1991;41:1015–20. 10. Delahaye JP, Mann JM, Poncet JH. Cerebrovascular accidents in infective endocarditis: role of anticoagulation. Eur Heart J 1990;11:1074–8. 11. Roder BL, Wandall DA, Espersen F, et al. Neurologic manifestations in Staphylococcus aureus endocarditis: a review of 260 bacteremic cases in nondrug addicts. Am J Med 1997;102:379–86. 12. Madinier IM, Fosse TB, Hitzig C, et al. Resistance profile survey of 50 periodontal strains of Actinobacillus actinomycetemcomitans. J Periodontol 1999;70:888–92.
November 2007 Volume 334 Number 5