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Fatal Streptococcus viridans (S. oralis) aortic prosthetic valve endocarditis (PVE) with paravalvular abscesses related to steroids
ISSUES IN INFECTIOUS DISEASE
Fatal Streptococcus viridans (S. oralis) aortic prosthetic valve endocarditis (PVE) with paravalvular abscesses related to steroids Laurence Turnier, PA, Sara Nausheen, MD, and Burke A. Cunha, MD
S
treptococcus viridans (ie, the viridans Streptococci) is a term for avirulent, noninvasive, commensals whose primary habitat is the oral pharynx. Because of their lack of virulence and invasive potential, S. viridans virtually causes only subacute endocarditis (SBE). To cause SBE, the viridans streptococcal species require a damaged endothelium and heart valve to adhere to for the infectious process to be initiated. The frequency distribution of viridans streptococcal strains associated with SBE is directly related to their ability to produce capsule important for adherence. Strains with capsules are more frequently associated in SBE than those species with less abundant capsules. Viridans streptococci rarely cause native prosthetic valve endocarditis (PVE). Clinically, SBE caused by viridans streptococci is characterized by temperatures of less than 102°F with a cardiac murmur and may be accompanied by splenomegaly and peripheral manifestations. S. viridans SBE rarely results in valvular destruction or perivalvular abscesses. In contrast, acute bacterial endocarditis caused by virulent pathogens (eg, Staphylococcus aureus) is capable of infecting and destroying normal heart valves and is often accompanied by congestive heart failure, septic emboli, and perivalvular abscess and leaks. PVE may involve mechanical or bioprosthetic valves and clinical presentation, and the severity depends on the pathogen and number of valves affected. The clinical course of PVE caused by relatively avirulent pathogens resembles SBE caused by viridans streptococci. There are little data on the untoward effects From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York; and State University of New York School of Medicine, Stony Brook, New York. Corresponding author: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. 0147-9563/$ – see front matter Copyright © 2009 by Mosby, Inc. doi:10.1016/j.hrtlng.2007.12.008
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of steroids in patients with S. viridans SBE. We present a case of aortic PVE caused by S. oralis, a viridans streptococcus, treated with steroids. Postmortem examination revealed aortic prosthetic valve involvement with two large periaortic valvular abscesses and a large perivalvular leak that, despite appropriate antibiotic treatment, led to the patient’s precipitous demise. We believe this is the first reported case of fatal aortic valve PVE caused by S. oralis related to steroids. Subacute bacterial endocarditis (SBE) refers to a subacute infection of the cardiac endothelium or cardiac valves. SBE is usually caused by relatively avirulent pathogens (ie, Streptococcus viridans) that require a damaged endothelium or heart valve to initiate infection. S. viridans is a misnomer and is not a single organism but rather represents a large group of “viridans streptococci” that vary in their frequency and ability to cause SBE. SBE requires an underlying cardiac abnormality within the heart and a bacteremia by the causative organism. The organisms causing bacteremia may cause SBE if they are able to attach to the damaged endothelial surface or heart valve. The ability to attach to a damaged endothelial surface or heart valve depends on the extent of capsular material produced by each viridans streptococcal species. Viridans streptococci that produce abundant capsule material are best able to adhere to a damaged endothelial surface or heart valve, and for this reason they are the most frequently implicated pathogens in SBE. The frequency and distribution regarding the ability of the viridans streptococci as pathogens in SBE relates directly to the amount of capsular material produced. In experiments, the same organisms devoid of capsules are rendered nonpathogenic because of their inability to adhere to a damaged endothelial surface or heart valve and initiate the infective process. Because of their relative avirulence, members
www.heartandlung.org
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of the S. viridans group are rare causes of SBE involving normal heart valves.1-3 SBE is clinically characterized by continuous bacteremia in the presence of a heart murmur. The diagnosis of SBE depends on demonstrating intracardiac vegetation and an otherwise unexplained high-grade bacteremia caused by a known endocarditis pathogen. S. viridans SBE is characterized by low-grade fevers (ⱕ102°F), and an unchanging murmur since, by definition, the infection is subacute. Shaking and chills are not a feature of S. viridans SBE. S. viridans SBE may be accompanied by a variety of peripheral manifestations (eg, splinter hemorrhages, Osler nodes, Roth’s spots) and splenomegaly. There are a variety of nonspecific laboratory findings that commonly accompany SBE: a highly elevated erythrocyte sedimentation rate (ESR), positive rheumatoid factors, and a biologically false-positive Venereal Disease Research Laboratory [test for syphilis]. Microscopic hematuria is a frequent finding in SBE and a reflection of the focal glomerular nephritis that regularly accompanies S. viridans SBE. Because of the noninvasive nature of the S. viridans, valvular destruction and heart failure are rare complications in SBE. Viridans staphylococci does not form paravalvular abscesses in the absence of immunosuppression.1-4 In contrast, acute bacterial endocarditis (ABE) is caused by virulent pathogens (ie, S. aureus). Invasive virulent pathogens (eg, S. aureus) are capable of attacking both damaged and normal heart valves. ABE is accompanied by high spiking fevers (ⱖ102°F) and a high-grade, continuous bacteremia. A heart murmur is usually not present before there is valvular destruction. A new murmur is often audible when valvular destruction begins. Septic embolic phenomena, myocardial abscesses, and valve destruction may complicate ABE. For these reasons, ABE is often a medical emergency requiring interventions, that is, cardiac valvular replacement. Virtually all of the fatalities related to complications of endocarditis are related to ABE and not SBE. ABE is accompanied by some of the nonspecific laboratory abnormalities that accompany SBE. Often the ESR is modestly elevated in the 30 to 75 mm/h range versus the highly elevated ESR rates associated with SBE, which are often ⱖ100 mm/h. Biologically falsepositive Venereal Disease Research Laboratory [test for syphilis] and positive rheumatoid factors are not usually a feature of ABE because by definition ABE is acute and there is usually insufficient time for these abnormalities to appear. It is said that all of the manifestations of SBE would be present in ABE
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if patients with ABE were left untreated for long enough. Because ABE is often caused by virulent pathogens (eg, S. aureus), ABE is frequently complicated by paravalvular abscesses and leak.1,5,6 Prosthetic valve endocarditis (PVE) involves an infection of the prosthetic cardiac valve or related supporting structures. PVE is most commonly caused by the same pathogens that cause ABE (ie, S. aureus) but may be caused by less virulent pathogens (eg, S. epidermidis, also known as the coagulasenegative staphylococci), but viridans streptococci are a rare cause of PVE. The diagnosis of PVE is made when there is a demonstrable cardiac vegetation involving the prosthetic cardiac valve and a high-grade, continuous bacteremia caused by a known endocarditis pathogen. As in SBE and ABE, PVE may be accompanied by peripheral embolic phenomenon.1,7 PVE caused by virulent pathogens (eg, S. aureus) may be complicated by paravalvular leak. It is well known that steroids may mask the symptoms of infection and promote the growth and proliferation of some microorganisms. Steroid therapy inhibits T-lymphocyte function and cell-mediated immunity. Chronic steroid use induces a leukocytosis and depletes T lymphocytes with relative lymphopenia. Steroid therapy exerts a permissive effect on intracellular pathogens usually suppressed by T lymphocytes, which mediate cell-mediated immunity. Steroid therapy has rarely been associated with adverse outcomes in patients with bacterial endocarditis with SBE. We present a case of S. oralis with aortic PVE.
ILLUSTRATIVE CASE A 42-year-old woman with a history of aortic valve replacement for rheumatic heart disease presented with chest pain and shortness of breath 1 day before admission. She had seen her physician for fever and fatigue 2 months before admission. She was diagnosed with Epstein-Barr virus and started on a course of steroids that initially provided “slight improvement” in her symptoms. One week before admission, she had a fever up to 102°F associated with chills, night sweats, and worsening fatigue. At the time of admission her prednisone dose had be tapered to 10 mg (by mouth) every 12 hours. On admission, she was afebrile with a temperature of 97.8°F, blood pressure of 130/80 mm Hg, and pulse of 85 beats/min. The physical examination results were unremarkable except for the cardiac examination, which revealed a III/VI blowing aortic
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Fatal S. viridans PVE
Fig 1 Transthoracic echocardiography showing vegetation on the aortic prosthetic valve.
murmur in the third left intercoastal space radiating along the left sternal border. Her lungs were clear to auscultation. There was no hepatosplenomegaly on abdominal examination. There were no peripheral manifestations of endocarditis. Admission laboratory tests included a white blood cell count of 16.5 K/mm3, hemoglobin/hematocrit of 10.1/29.3 g/dL, and platelet count of 241 K/mm3. Renal and liver function test results were within normal limits. The ESR was 100 mm/h, and C-reactive protein was 357 mg/dL. Her ferritin serum level was 785 ng/mL. Cardiac enzymes on admission were unremarkable (creatine phosphokinase of 42, MB of 1.0, and troponin level of 0.3 ng/dL). Three days later, troponin levels peaked at 6.2 ng/dL. Blood cultures from admission were positive for S. viridans subspeciated as S. oralis. The patient was allergic to penicillin and was initially treated with vancomycin and gentamicin. After a negative penicillin skin test, vancomycin was discontinued and ceftriaxone 2 g (intravenously) every 24 hours was started. Initial chest, abdomen, and pelvis computed tomography scans showed splenomegaly with a single splenic hypodensity. Transthoracic echocardiography performed 1 day after admission was negative for vegetations, but transesophageal echocardiography 1 day later showed multiple, mobile, prolapsing vegetations on
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the bioprosthetic aortic valve leaflets. Also noted on transesophageal echocardiography were two large aortic paravalvular abscesses and a severe paravalvular leak. (Figures 1, 2) Four days later, the patient’s condition rapidly deteriorated and she was intubated for severe respiratory distress. She was taken for urgent aortic root and valve replacement but did not survive surgery. There was evidence of a recent acute myocardial infarction, which was not considered the cause of death. At postmortem, the organisms were present on stained preparations of the aortic valve prosthesis and paravalvular abscesses.
DISCUSSION Steroids in SBE may lead to a delay in diagnosis.8-11 In this case the patient received steroids from her primary care physician who thought that she had Epstein-Barr virus infection to explain the symptoms of fatigue and low-grade fevers. Steroids masked the patient’s symptoms for weeks, leading to a delay in diagnosis and resulting in treatment failure. Steroids mask the symptoms of SBE and have also been shown in experimental models to prolong bacteremia and inhibit sterilization of vegetations
www.heartandlung.org
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Turnier, Nausheen, and Cunha
Fig 2 Transthoracic echocardiography showing two large paravalvular abscesses on the aortic prosthetic valve.
by directly inhibiting phagocytosis indirectly by inhibiting cell-mediated immunity. Francioli and Freedman8 showed that artificially induced Streptococcus sanguis vegetations in experimental rabbit models were sterilized in all parts of the vascular system except the left side of the heart by host defense mechanisms and that these defense mechanisms were inhibited by steroids.8 Butler and colleagues9 showed that the severity of endocarditis was enhanced by steroids in dysgonic fermenter 2 (DF-2) endocarditis in rabbit models.9 Because SBE is often accompanied by muscular skeletal symptoms, rheumatic diseases often mimic endocarditis.1,12-18 Steroids are often used to treat various rheumatic disorders because of their immunosuppressive effects. However, patients with SBE who have muscular skeletal systems misdiagnosed as rheumatic disorders may be inappropriately treated with steroids. Steroids may have a definite negative adverse effect in patients with endocarditis. Furthermore, clinicians may be misled by the presence of laboratory tests, which are usually associated with rheumatic disorders but have also been associated with SBE, that is, antineutrophilic cytoplasmic antibodies. Clinicians must also be aware that antineutrophilic cytoplasmic antibody
170
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positivity may occur with rheumatic diseases but also may be a nonspecific laboratory finding of SBE.19,20 Clinicians must be vigilant not to ascribe all patients with low-grade fevers, malaise, and muscular skeletal symptoms to a rheumatic process, particularly patients with prosthetic heart valves. The teaching lesson from this case is that the diagnosis of SBE should be considered in patients presenting with nonspecific constitutional symptoms and low-grade fever, particularly if they have prosthetic valves, before using systemic steroids. Steroids not only mask symptoms but also delay the diagnosis and worsen outcomes in SBE, altering host defenses.
REFERENCES 1. Brusch JL. Infective endocarditis. New York, NY: Informa Healthcare; 2007. 2. Watanakunakorn C, Burket T. Infectious endocarditis at a large community teaching hospital, 1980-1990. Medicine (Baltimore) 1993;72-90. 3. Pelletier LL, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 19631972. Medicine (Baltimore) 1977;56:287-8. 4. Kurland S, Enghoff E, Landelius J, et al. A 10-year retrospective study of infective endocarditis at a university hospital
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5. 6. 7. 8.
9.
10. 11.
with special regard to the timing of surgical evaluation in S. viridans endocarditis. Scand J Infect Dis 1999;87-91. Cunha BA, Gill MV, Lazar J. Acute infective endocarditis. Infect Dis Clin North Am 1996;10:811-34. Kim N, Lazar J, Cunha BA. Temperatures ⱖ102°F as a prognostic feature of acute bacterial endocarditis. Infect Dis Pract 1999;23:90-2. Horstkotte D, Piper C, Niehues R, et al. Late prosthetic valve endocarditis. Eur Heart J 1995;B:39-47. Francioli PB, Freedman LR. Streptococcal infection of endocardial and other intravascular vegetations in rabbits: natural history and effect of dexamethasone. Infect Immun 1979; 24:483-91. Butler T, Johnston KH, Gutierrez Y, et al. Enhancement of experimental bacteremia and endocarditis caused by dysgenic fermenter (DF-2) bacterium after treatment with methylprednisolone and after splenectomy. Infect Immun 1985;47: 294-300. Maglioni E, Garosi M, Marchetti L, et al. Infectious endocarditis due to Staphylococcus aureus involving 3 cardiac valves. Minerva Anestesiol 2003;69:583-90. Butler T, Johnston KH, Gutierrez Y, et al. Enhancement of experimental bacteremia and endocarditis caused by dysgenic fermenter (DF-2 bacterium after treatment with methylprednisolone and after splenectomy. Infect Immun 1985; 47:294-300.
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Fatal S. viridans PVE 12. Iqbal MB, Fisher NG, Fox KM. Vasculitis masquerading as aortic valve endocarditis: Heart 2005;91:e37. 13. Spomer A, Ho G Jr. Bacterial endocarditis and septic arthritis presenting as polymyalgia rheumatica. Arch Intern Med 1997; 157:162-8. 14. Agarwas A, Clements S, Sedmak D, et al. Subacute bacterial endocarditis masqueriding at Type III essential mixed cryoglobulinemia. J Am Soc Nephrol 1997;8:1971-6. 15. Churchill MA Jr, Geraci JE, Hunder GG. Musculoskeletal manifestations of bacterial endocarditis. Ann Intern Med 1977; 87:754-9. 16. Meyers OL, Commerford PJ. Musculoskeletal manifestations of bacterial endocarditis. Ann Rheum Dis 1977;36:517-9. 17. Levo Y, Nashif M. Musculoskeletal manifestations of bacterial endocarditis. Clin Exp Rheumatol 1983;1:49-52. 18. Llinas L, Harrington T. Musculoskeletal manifestations as the initial presentation of infective endocarditis. South Med J 2005;98:127-8. 19. Choi HK, Lamprecht P, Niles JL, et al. Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies. Arthritis Rheum 2000;430:226-31. 20. deCorla-Souza A, Cunha BA. Streptococcal viridans bacterial endocarditis associated with anti-neutrophil cytoplasmic autoantibodies (ANCA). Heart Lung 2003;32:140-3.
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Fatal Streptococcus viridans (S. oralis) aortic prosthetic valve endocarditis (PVE) with paravalvular abscesses related to steroids Laurence Turnier, PA, Sara Nausheen, MD, and Burke A. Cunha, MD
S
treptococcus viridans (ie, the viridans Streptococci) is a term for avirulent, noninvasive, commensals whose primary habitat is the oral pharynx. Because of their lack of virulence and invasive potential, S. viridans virtually causes only subacute endocarditis (SBE). To cause SBE, the viridans streptococcal species require a damaged endothelium and heart valve to adhere to for the infectious process to be initiated. The frequency distribution of viridans streptococcal strains associated with SBE is directly related to their ability to produce capsule important for adherence. Strains with capsules are more frequently associated in SBE than those species with less abundant capsules. Viridans streptococci rarely cause native prosthetic valve endocarditis (PVE). Clinically, SBE caused by viridans streptococci is characterized by temperatures of less than 102°F with a cardiac murmur and may be accompanied by splenomegaly and peripheral manifestations. S. viridans SBE rarely results in valvular destruction or perivalvular abscesses. In contrast, acute bacterial endocarditis caused by virulent pathogens (eg, Staphylococcus aureus) is capable of infecting and destroying normal heart valves and is often accompanied by congestive heart failure, septic emboli, and perivalvular abscess and leaks. PVE may involve mechanical or bioprosthetic valves and clinical presentation, and the severity depends on the pathogen and number of valves affected. The clinical course of PVE caused by relatively avirulent pathogens resembles SBE caused by viridans streptococci. There are little data on the untoward effects From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York; and State University of New York School of Medicine, Stony Brook, New York. Corresponding author: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. 0147-9563/$ – see front matter Copyright © 2009 by Mosby, Inc. doi:10.1016/j.hrtlng.2007.12.008
HEART & LUNG
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of steroids in patients with S. viridans SBE. We present a case of aortic PVE caused by S. oralis, a viridans streptococcus, treated with steroids. Postmortem examination revealed aortic prosthetic valve involvement with two large periaortic valvular abscesses and a large perivalvular leak that, despite appropriate antibiotic treatment, led to the patient’s precipitous demise. We believe this is the first reported case of fatal aortic valve PVE caused by S. oralis related to steroids. Subacute bacterial endocarditis (SBE) refers to a subacute infection of the cardiac endothelium or cardiac valves. SBE is usually caused by relatively avirulent pathogens (ie, Streptococcus viridans) that require a damaged endothelium or heart valve to initiate infection. S. viridans is a misnomer and is not a single organism but rather represents a large group of “viridans streptococci” that vary in their frequency and ability to cause SBE. SBE requires an underlying cardiac abnormality within the heart and a bacteremia by the causative organism. The organisms causing bacteremia may cause SBE if they are able to attach to the damaged endothelial surface or heart valve. The ability to attach to a damaged endothelial surface or heart valve depends on the extent of capsular material produced by each viridans streptococcal species. Viridans streptococci that produce abundant capsule material are best able to adhere to a damaged endothelial surface or heart valve, and for this reason they are the most frequently implicated pathogens in SBE. The frequency and distribution regarding the ability of the viridans streptococci as pathogens in SBE relates directly to the amount of capsular material produced. In experiments, the same organisms devoid of capsules are rendered nonpathogenic because of their inability to adhere to a damaged endothelial surface or heart valve and initiate the infective process. Because of their relative avirulence, members
www.heartandlung.org
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Fatal S. viridans PVE
of the S. viridans group are rare causes of SBE involving normal heart valves.1-3 SBE is clinically characterized by continuous bacteremia in the presence of a heart murmur. The diagnosis of SBE depends on demonstrating intracardiac vegetation and an otherwise unexplained high-grade bacteremia caused by a known endocarditis pathogen. S. viridans SBE is characterized by low-grade fevers (ⱕ102°F), and an unchanging murmur since, by definition, the infection is subacute. Shaking and chills are not a feature of S. viridans SBE. S. viridans SBE may be accompanied by a variety of peripheral manifestations (eg, splinter hemorrhages, Osler nodes, Roth’s spots) and splenomegaly. There are a variety of nonspecific laboratory findings that commonly accompany SBE: a highly elevated erythrocyte sedimentation rate (ESR), positive rheumatoid factors, and a biologically false-positive Venereal Disease Research Laboratory [test for syphilis]. Microscopic hematuria is a frequent finding in SBE and a reflection of the focal glomerular nephritis that regularly accompanies S. viridans SBE. Because of the noninvasive nature of the S. viridans, valvular destruction and heart failure are rare complications in SBE. Viridans staphylococci does not form paravalvular abscesses in the absence of immunosuppression.1-4 In contrast, acute bacterial endocarditis (ABE) is caused by virulent pathogens (ie, S. aureus). Invasive virulent pathogens (eg, S. aureus) are capable of attacking both damaged and normal heart valves. ABE is accompanied by high spiking fevers (ⱖ102°F) and a high-grade, continuous bacteremia. A heart murmur is usually not present before there is valvular destruction. A new murmur is often audible when valvular destruction begins. Septic embolic phenomena, myocardial abscesses, and valve destruction may complicate ABE. For these reasons, ABE is often a medical emergency requiring interventions, that is, cardiac valvular replacement. Virtually all of the fatalities related to complications of endocarditis are related to ABE and not SBE. ABE is accompanied by some of the nonspecific laboratory abnormalities that accompany SBE. Often the ESR is modestly elevated in the 30 to 75 mm/h range versus the highly elevated ESR rates associated with SBE, which are often ⱖ100 mm/h. Biologically falsepositive Venereal Disease Research Laboratory [test for syphilis] and positive rheumatoid factors are not usually a feature of ABE because by definition ABE is acute and there is usually insufficient time for these abnormalities to appear. It is said that all of the manifestations of SBE would be present in ABE
168
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if patients with ABE were left untreated for long enough. Because ABE is often caused by virulent pathogens (eg, S. aureus), ABE is frequently complicated by paravalvular abscesses and leak.1,5,6 Prosthetic valve endocarditis (PVE) involves an infection of the prosthetic cardiac valve or related supporting structures. PVE is most commonly caused by the same pathogens that cause ABE (ie, S. aureus) but may be caused by less virulent pathogens (eg, S. epidermidis, also known as the coagulasenegative staphylococci), but viridans streptococci are a rare cause of PVE. The diagnosis of PVE is made when there is a demonstrable cardiac vegetation involving the prosthetic cardiac valve and a high-grade, continuous bacteremia caused by a known endocarditis pathogen. As in SBE and ABE, PVE may be accompanied by peripheral embolic phenomenon.1,7 PVE caused by virulent pathogens (eg, S. aureus) may be complicated by paravalvular leak. It is well known that steroids may mask the symptoms of infection and promote the growth and proliferation of some microorganisms. Steroid therapy inhibits T-lymphocyte function and cell-mediated immunity. Chronic steroid use induces a leukocytosis and depletes T lymphocytes with relative lymphopenia. Steroid therapy exerts a permissive effect on intracellular pathogens usually suppressed by T lymphocytes, which mediate cell-mediated immunity. Steroid therapy has rarely been associated with adverse outcomes in patients with bacterial endocarditis with SBE. We present a case of S. oralis with aortic PVE.
ILLUSTRATIVE CASE A 42-year-old woman with a history of aortic valve replacement for rheumatic heart disease presented with chest pain and shortness of breath 1 day before admission. She had seen her physician for fever and fatigue 2 months before admission. She was diagnosed with Epstein-Barr virus and started on a course of steroids that initially provided “slight improvement” in her symptoms. One week before admission, she had a fever up to 102°F associated with chills, night sweats, and worsening fatigue. At the time of admission her prednisone dose had be tapered to 10 mg (by mouth) every 12 hours. On admission, she was afebrile with a temperature of 97.8°F, blood pressure of 130/80 mm Hg, and pulse of 85 beats/min. The physical examination results were unremarkable except for the cardiac examination, which revealed a III/VI blowing aortic
MARCH/APRIL 2009
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Turnier, Nausheen, and Cunha
Fatal S. viridans PVE
Fig 1 Transthoracic echocardiography showing vegetation on the aortic prosthetic valve.
murmur in the third left intercoastal space radiating along the left sternal border. Her lungs were clear to auscultation. There was no hepatosplenomegaly on abdominal examination. There were no peripheral manifestations of endocarditis. Admission laboratory tests included a white blood cell count of 16.5 K/mm3, hemoglobin/hematocrit of 10.1/29.3 g/dL, and platelet count of 241 K/mm3. Renal and liver function test results were within normal limits. The ESR was 100 mm/h, and C-reactive protein was 357 mg/dL. Her ferritin serum level was 785 ng/mL. Cardiac enzymes on admission were unremarkable (creatine phosphokinase of 42, MB of 1.0, and troponin level of 0.3 ng/dL). Three days later, troponin levels peaked at 6.2 ng/dL. Blood cultures from admission were positive for S. viridans subspeciated as S. oralis. The patient was allergic to penicillin and was initially treated with vancomycin and gentamicin. After a negative penicillin skin test, vancomycin was discontinued and ceftriaxone 2 g (intravenously) every 24 hours was started. Initial chest, abdomen, and pelvis computed tomography scans showed splenomegaly with a single splenic hypodensity. Transthoracic echocardiography performed 1 day after admission was negative for vegetations, but transesophageal echocardiography 1 day later showed multiple, mobile, prolapsing vegetations on
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the bioprosthetic aortic valve leaflets. Also noted on transesophageal echocardiography were two large aortic paravalvular abscesses and a severe paravalvular leak. (Figures 1, 2) Four days later, the patient’s condition rapidly deteriorated and she was intubated for severe respiratory distress. She was taken for urgent aortic root and valve replacement but did not survive surgery. There was evidence of a recent acute myocardial infarction, which was not considered the cause of death. At postmortem, the organisms were present on stained preparations of the aortic valve prosthesis and paravalvular abscesses.
DISCUSSION Steroids in SBE may lead to a delay in diagnosis.8-11 In this case the patient received steroids from her primary care physician who thought that she had Epstein-Barr virus infection to explain the symptoms of fatigue and low-grade fevers. Steroids masked the patient’s symptoms for weeks, leading to a delay in diagnosis and resulting in treatment failure. Steroids mask the symptoms of SBE and have also been shown in experimental models to prolong bacteremia and inhibit sterilization of vegetations
www.heartandlung.org
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Turnier, Nausheen, and Cunha
Fig 2 Transthoracic echocardiography showing two large paravalvular abscesses on the aortic prosthetic valve.
by directly inhibiting phagocytosis indirectly by inhibiting cell-mediated immunity. Francioli and Freedman8 showed that artificially induced Streptococcus sanguis vegetations in experimental rabbit models were sterilized in all parts of the vascular system except the left side of the heart by host defense mechanisms and that these defense mechanisms were inhibited by steroids.8 Butler and colleagues9 showed that the severity of endocarditis was enhanced by steroids in dysgonic fermenter 2 (DF-2) endocarditis in rabbit models.9 Because SBE is often accompanied by muscular skeletal symptoms, rheumatic diseases often mimic endocarditis.1,12-18 Steroids are often used to treat various rheumatic disorders because of their immunosuppressive effects. However, patients with SBE who have muscular skeletal systems misdiagnosed as rheumatic disorders may be inappropriately treated with steroids. Steroids may have a definite negative adverse effect in patients with endocarditis. Furthermore, clinicians may be misled by the presence of laboratory tests, which are usually associated with rheumatic disorders but have also been associated with SBE, that is, antineutrophilic cytoplasmic antibodies. Clinicians must also be aware that antineutrophilic cytoplasmic antibody
170
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positivity may occur with rheumatic diseases but also may be a nonspecific laboratory finding of SBE.19,20 Clinicians must be vigilant not to ascribe all patients with low-grade fevers, malaise, and muscular skeletal symptoms to a rheumatic process, particularly patients with prosthetic heart valves. The teaching lesson from this case is that the diagnosis of SBE should be considered in patients presenting with nonspecific constitutional symptoms and low-grade fever, particularly if they have prosthetic valves, before using systemic steroids. Steroids not only mask symptoms but also delay the diagnosis and worsen outcomes in SBE, altering host defenses.
REFERENCES 1. Brusch JL. Infective endocarditis. New York, NY: Informa Healthcare; 2007. 2. Watanakunakorn C, Burket T. Infectious endocarditis at a large community teaching hospital, 1980-1990. Medicine (Baltimore) 1993;72-90. 3. Pelletier LL, Petersdorf RG. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 19631972. Medicine (Baltimore) 1977;56:287-8. 4. Kurland S, Enghoff E, Landelius J, et al. A 10-year retrospective study of infective endocarditis at a university hospital
MARCH/APRIL 2009
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Turnier, Nausheen, and Cunha
5. 6. 7. 8.
9.
10. 11.
with special regard to the timing of surgical evaluation in S. viridans endocarditis. Scand J Infect Dis 1999;87-91. Cunha BA, Gill MV, Lazar J. Acute infective endocarditis. Infect Dis Clin North Am 1996;10:811-34. Kim N, Lazar J, Cunha BA. Temperatures ⱖ102°F as a prognostic feature of acute bacterial endocarditis. Infect Dis Pract 1999;23:90-2. Horstkotte D, Piper C, Niehues R, et al. Late prosthetic valve endocarditis. Eur Heart J 1995;B:39-47. Francioli PB, Freedman LR. Streptococcal infection of endocardial and other intravascular vegetations in rabbits: natural history and effect of dexamethasone. Infect Immun 1979; 24:483-91. Butler T, Johnston KH, Gutierrez Y, et al. Enhancement of experimental bacteremia and endocarditis caused by dysgenic fermenter (DF-2) bacterium after treatment with methylprednisolone and after splenectomy. Infect Immun 1985;47: 294-300. Maglioni E, Garosi M, Marchetti L, et al. Infectious endocarditis due to Staphylococcus aureus involving 3 cardiac valves. Minerva Anestesiol 2003;69:583-90. Butler T, Johnston KH, Gutierrez Y, et al. Enhancement of experimental bacteremia and endocarditis caused by dysgenic fermenter (DF-2 bacterium after treatment with methylprednisolone and after splenectomy. Infect Immun 1985; 47:294-300.
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