CASE REPORTS
Subacute Bacterial Endocarditis Secondary to Streptococcus pneumoniae MICHAELS. GELFAND,M.D., MICHAELG. THRELKELD,M.D., Memphis, Tennessee
Pnwmococcal endocarditis characteristically presents as an acute illness, often accompanied by purulent meningitis, rapid destruction of the heart valves, congestive heart failure, and high mortality. We describe two patients with subacute pneumococcal endocarditis without a known primary source of pneumococcal bacteremia, fever, meningitis, or congestive heart failure. Both patients were cured with medical therapy. Pneumococcal endocarditis can present as an indolent illnw Mmbliug viridaus streptococcal endocarditis.
neumococcalendocarditishasbecomea rare illP nessin the antibiotic era,causing1%to 3%of all casesof native valve endocarditis [l]. Pneumococcal endocarditis characteristically presents as an acuteandsevereillnessusually accompaniedby purulent meningitis and resulting in the rapid destruction of the heart valves,congestiveheart failure, and high mortality [2]. We haverecentlytreated two patients with pneumococcalendocarditiswho presentedwith an indolent, subacute illness, without a known primary sourceof pneumococcalbacteremia,fever,meningitis, or congestiveheart failure. Both patients were cured with medical therapy. CASEREPORTS Patient 1
From the Department of internal Medicine, Methodist Hospitals of Memphis, Memphis, Tennessee. Requests for reprints should be addressed to Michael S. Gelfand, M.D., 188 South Bellevue, Suite 419, Methodist Hospitals of Memphis, Memphis, Tennessee 38104. Manuscript submitted February 14, 1991, and accepted in revised form July 5, 1991.
An 82-year-oldfemale patient was hospitalized with a 5-month history of weakness,malaise, and 20-poundweight loss. One month prior to the admission, an outpatient evaluation showeda hematocrit of 31%,erythrocyte sedimentation rate (ESR) of 65 mm/h, and microscopic hematuria. A bone marrow biopsy, serum protein electrophoresis,serum iron studies, computed tomographic scan of the abdomen, and cystoscopyfailed to reveal an etiology of the anemia or hematuria. The patient was afebrile on severaloccasions.Two setsof blood cultures were obtained and grew Streptococcus pneumoniae. The patient washospitalized.She receivedno antibiotics during the 5-month period prior to the admission.The patient was a thin elderly woman in no acutedistresswith a blood pressureof 140/92mm Hg, pulse of 82/min, and an oral temperature of 37.2OC.Lungs were clear on auscultation. A gradeIII/VI harsh holosystolicmurmur was presentat the apexwith radiation to the left lower sternal border and the left axilla. The liver and spleen were not palpable. There were no fundustopic, mucosal,or cutaneoussigns of endocarditis. Laboratory tests showeda hematocrit of 26.1%and a white blood cell count of 9,900/mm3,with 82% polymorphonuclearneutrophils, 14%lymphocytes, and 4% monocytes. The platelet count was 161,000/mm3,and the ESR was74mm/h. A urinalysis showeda trace of protein and 60 to 80 red blood cells per high-power field. No red blood cell casts were seen.Serum blood urea nitrogen (BUN) was July 1992 The American Journal of Medicine
Volume 93
91
SUBACUTE PNEUMGCOCCAL ENDOCARDITIS/ GELFAND AND THRELKELD
47 mg/dL, and serum creatinine was 3.7 mg/dL. Three more sets of blood cultures were obtained and grew cY-hemolytic, optochin-sensitive streptococci confirmed as S. pneumoniae by a biochemical panel (Pos Combo Panel, Microscan, Sacramento, CA). The organism was not serotyped. Serum rheumatoid factor assay was negative, and C3 and C4 complement component levels were within normal limits. Serum immune complexes were detected by Raji cell assay and protein A binding assay. Chest radiography showed a slight cardiomegaly and clear lung fields. An echocardiogram showed severe mitral regurgitation and left atrial dilatation. No valvular vegetations were seen. Penicillin G, 2 million units intravenously every 4 hours, was administered for 4 weeks. Blood cultures were negative at 7 days of therapy. Three months after the completion of therapy, fatigue and weakness have resolved, and the patient has gained 10 pounds. Hematocrit, ESR, serum BUN, and creatinine have returned to normal levels, and microscopic hematuria has resolved. Patient 2 A 68-year-old woman presented to the hospital with a l-month history of musculoskeletal pains in the right shoulder and lower back, malaise, chills, and subjective fever. Physical examination revealed a blood pressure of 150/80 mm Hg, pulse of 70 beat.s/min, and normal temperature. She did not appear acutely ill. Chest was clear on auscultation. A III/VI holosystolic murmur was audible at the cardiac apex and the left lower sternal border with radiation to the left axilla. The liver and spleen were not palpable. There were no funduscopic, mucosal, or cutaneous signs of endocarditis. Musculoskeletal examination revealed diffuse tenderness over the right shoulder joint and the lower back. The hematocrit was 34%, and the white blood cell count was 15,600/mm3 with 83% segmented neutrophils, 10% bands, and 70% lymphocytes. Urinalysis was within normal limits. ESR was 74 mm/h. Serum immunoglobulin levels were within normal limits. The chest radiograph was unremarkable. The patient remained afebrile. Four sets of blood cultures grew S. pneumoniae, serotype 38 (Tennessee Department of Public Health, Nashville, TN; Dr. Barry Gray, University of Alabama School of Medicine, Birmingham, AL). An echocardiogram showed moderate mitral regurgitation, but no vegetations. Intravenous penicillin G, 4 million units every 4 hours, was given for 4 weeks with a rapid resolution of malaise, musculoskeletal symptoms, and chills. Elevated ESR and white blood cell count returned to normal levels. The patient remained free of
92
July 1992 The American Journal of Medicine
Volume 93
symptoms therapy.
4 months
after
the completion
of
COMMENTS Pneumococcal endocarditis is an acute severe illness, resembling acute Staphylococcus aureus endocarditis [l-3]. Pneumococcal pneumonia or sinusitis is the usual source of bacteremic seeding of the cardiac valve [3]. Normal heart valves can be infected, and there is a predilection for aortic valve [ 11. Older male alcoholics constitute the majority of patients reported in the literature [4]. The clinical picture is that of an acutely ill, febrile, often comatose patient with septicemia and purulent meningitis [2]. Rapid destruction of the heart valve results in valvular insufficiency, acute congestive heart failure, and high mortality [l-4]. A subacute presentation of pneumococcal endocarditis has very rarely been described (Robert Austrian, M.D., personal communication). Powderly et al [5] reported two patients with a subacute presentation of pneumococcal endocarditis. The clinical course of our patients was remarkable for the absence of the usual characteristics of pneumococcal endocarditis. When cy-hemolytic streptococci grew from blood cultures, subacute bacterial endocarditis secondary to viridans streptococci was suspected in our patients. Both patients were female, were not alcoholics, and presented with a subacute indolent illness. Neither had a fever, pneumonia, or meningitis. The mitral valve was involved in both cases. Medical therapy alone was successful. Both of our patients were elderly. The clinical presentation of endocarditis in the elderly tends to be more indolent and with fewer symptoms than are reported in younger patients [6]. The frequent absence of a febrile response is well recognized in the elderly patients with infective endocarditis [6-8]. In elderly patients with bacterial endocarditis who do develop fever, the height of the febrile response is diminished compared with younger patients [6]. There is little doubt that both of our patients did, in fact, have pneumococcal endocarditis. The absence of valvular vegetations on transthoracic echocardiography is not unexpected. In several published series, only approximately 50% of patients with bacterial endocarditis had valvular vegetations detected by transthoracic echocardiography [9]. Transesophageal echocardiography has a higher sensitivity for valvular vegetations but was not performed in our patients [lo]. Patients with welldocumented pneumococcal endocarditis and no vegetations on echocardiography have previously been reported [5,11]. Two of seven patients report-
SUBACUTE
ed by Powderly et al [5] and two of five patients reported by Bruyn et al [ll] had no valvular vegetations detected by transthoracic echocardiography. Elderly patients with bacterial endocarditis are less likely to have valvular vegetations detected by echocardiography than younger patients [S]. Pneumococcal bacteremia without an obvious primary focus occurs primarily in asplenic patients and in children less than 2 years old [ 121. Spitalny et al [12] reported three elderly patients with pneumococcal bacteremia without a primary focus. All three had an acute febrile illness, no clinical findings of endocarditis, and a serious underlying disease [12]. The clinical pictures in both of our patients fulfiied the strict clinical criteria for probable endocarditis, as defined by Fordham Von Reyn et al [ 131. The first patient had a total of five out of five sets of blood cultures, obtained over a 72-hour period, positive for S. pneumoniae. She had both auscultatory and echocardiographic evidence of severe mitral regurgitation. Hematuria and abnormal serum BUN and creatinine levels were suggestive of glomerulonephritis. No source of pneumococcal bacteremia, other than the heart, was found. Longstanding clinical and laboratory abnormalities resolved with penicillin G therapy. The second patient had four of four blood cultures positive for S. pneumoniae. Significant mitral regurgitation was found by both auscultation and echocardiography. No extracardiac source of pneumococcal bacteremia was apparent. The clinical and laboratory abnormalities resolved after penicillin G therapy. The majority of reported cases of pneumococcal endocarditis present with an acute, fulminant clinical picture [l-5]. Pneumococcal endocarditis can, however, present with an indolent clinical picture as exemplified by our patients. Such presentation
PNEUMDCDCCAL
ENDGCARDITIS
/ GELFAND
AND THRELKELD
of pneumococcal endocarditis is probably rare, but should be considered in the setting of subacute bacterial endocarditis secondary to a-hemolytic streptococci.
ACKNOWLEDGMENT We are indebted to Drs. Robert Austrian and Ralph Tompsett for their valuable advice and to Mrs. Pat McCullough for assistance in the preparation of the manuscript.
REFERENCES 1. Straus AL, Hamburger
M. Pneumococcal
endocarditis
in the penicillin era.
Arch Intern Med 1966; 118: 190-8. 2. Austrian R. Pneumococcal endocarditis, meningitis, and rupture of the aortic valve. Arch Intern Med 1957; 99: 539-44. 3. Wolff M. Regnier B. Witchitz S, Gilbert C, Amoudry C, Vachon F. Pneumococcal endocarditis. Eur Heart J 1984; 5 Suppl C: 77-80. 4. Buchbinder NA, Roberts WC. Alcoholism; an important but unemphasized factor predisposing to infective endocarditis. Arch Intern Med 1973; 132:
689-92. 5. Powderly WG, Stanley SL. Medoff G. Pneumococcal endocarditis: report of a series and review of the literature. Rev Infect Dis 1986; 8: 786-91. 6. Terpenning MS. Buggy BP, Kauffman CA. infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: 626-34. 7. Robbins N, DeMaria A, Miller MH. Infective endocarditis in the elderly. South Med J 1980; 73: 1335-8. 8. Applefeld MM, Hornick RB. Infective endocarditis in patients over age 60. Am Heart J 1974; 88: 90-4. 9. Steckelberg JM. Murphy JG, Ballard D. eta/. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med 1991; 114: 63640. 10. Mugge A. Daniel WG, Frank G, Lichtlen PR. Echocardiography in infectiie endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol 1989; 14: 631-8. 11. Bruyn GAW. Thompson J. Van Der Meer JWM. Pneumococcal endocarditis in adult patients. A report of five cases and review of the literature. Q J Med
1990; 74: 33-40. 12. Spitalny KC, Bromberg K. Ginsberg MB. Streptococcus pneumoniae bacteremia without an identifiable focus in adults. Johns Hopkins Med J 1982; 150:
36-7. 13. Fordham Von Reyn C, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981; 94: 506-18.
July 1992
The American
Journal
of Medicine
Volume
93
93
Subacute Bacterial Endocarditis Secondary to Streptococcus pneumoniae MICHAELS. GELFAND,M.D., MICHAELG. THRELKELD,M.D., Memphis, Tennessee
Pnwmococcal endocarditis characteristically presents as an acute illness, often accompanied by purulent meningitis, rapid destruction of the heart valves, congestive heart failure, and high mortality. We describe two patients with subacute pneumococcal endocarditis without a known primary source of pneumococcal bacteremia, fever, meningitis, or congestive heart failure. Both patients were cured with medical therapy. Pneumococcal endocarditis can present as an indolent illnw Mmbliug viridaus streptococcal endocarditis.
neumococcalendocarditishasbecomea rare illP nessin the antibiotic era,causing1%to 3%of all casesof native valve endocarditis [l]. Pneumococcal endocarditis characteristically presents as an acuteandsevereillnessusually accompaniedby purulent meningitis and resulting in the rapid destruction of the heart valves,congestiveheart failure, and high mortality [2]. We haverecentlytreated two patients with pneumococcalendocarditiswho presentedwith an indolent, subacute illness, without a known primary sourceof pneumococcalbacteremia,fever,meningitis, or congestiveheart failure. Both patients were cured with medical therapy. CASEREPORTS Patient 1
From the Department of internal Medicine, Methodist Hospitals of Memphis, Memphis, Tennessee. Requests for reprints should be addressed to Michael S. Gelfand, M.D., 188 South Bellevue, Suite 419, Methodist Hospitals of Memphis, Memphis, Tennessee 38104. Manuscript submitted February 14, 1991, and accepted in revised form July 5, 1991.
An 82-year-oldfemale patient was hospitalized with a 5-month history of weakness,malaise, and 20-poundweight loss. One month prior to the admission, an outpatient evaluation showeda hematocrit of 31%,erythrocyte sedimentation rate (ESR) of 65 mm/h, and microscopic hematuria. A bone marrow biopsy, serum protein electrophoresis,serum iron studies, computed tomographic scan of the abdomen, and cystoscopyfailed to reveal an etiology of the anemia or hematuria. The patient was afebrile on severaloccasions.Two setsof blood cultures were obtained and grew Streptococcus pneumoniae. The patient washospitalized.She receivedno antibiotics during the 5-month period prior to the admission.The patient was a thin elderly woman in no acutedistresswith a blood pressureof 140/92mm Hg, pulse of 82/min, and an oral temperature of 37.2OC.Lungs were clear on auscultation. A gradeIII/VI harsh holosystolicmurmur was presentat the apexwith radiation to the left lower sternal border and the left axilla. The liver and spleen were not palpable. There were no fundustopic, mucosal,or cutaneoussigns of endocarditis. Laboratory tests showeda hematocrit of 26.1%and a white blood cell count of 9,900/mm3,with 82% polymorphonuclearneutrophils, 14%lymphocytes, and 4% monocytes. The platelet count was 161,000/mm3,and the ESR was74mm/h. A urinalysis showeda trace of protein and 60 to 80 red blood cells per high-power field. No red blood cell casts were seen.Serum blood urea nitrogen (BUN) was July 1992 The American Journal of Medicine
Volume 93
91
SUBACUTE PNEUMGCOCCAL ENDOCARDITIS/ GELFAND AND THRELKELD
47 mg/dL, and serum creatinine was 3.7 mg/dL. Three more sets of blood cultures were obtained and grew cY-hemolytic, optochin-sensitive streptococci confirmed as S. pneumoniae by a biochemical panel (Pos Combo Panel, Microscan, Sacramento, CA). The organism was not serotyped. Serum rheumatoid factor assay was negative, and C3 and C4 complement component levels were within normal limits. Serum immune complexes were detected by Raji cell assay and protein A binding assay. Chest radiography showed a slight cardiomegaly and clear lung fields. An echocardiogram showed severe mitral regurgitation and left atrial dilatation. No valvular vegetations were seen. Penicillin G, 2 million units intravenously every 4 hours, was administered for 4 weeks. Blood cultures were negative at 7 days of therapy. Three months after the completion of therapy, fatigue and weakness have resolved, and the patient has gained 10 pounds. Hematocrit, ESR, serum BUN, and creatinine have returned to normal levels, and microscopic hematuria has resolved. Patient 2 A 68-year-old woman presented to the hospital with a l-month history of musculoskeletal pains in the right shoulder and lower back, malaise, chills, and subjective fever. Physical examination revealed a blood pressure of 150/80 mm Hg, pulse of 70 beat.s/min, and normal temperature. She did not appear acutely ill. Chest was clear on auscultation. A III/VI holosystolic murmur was audible at the cardiac apex and the left lower sternal border with radiation to the left axilla. The liver and spleen were not palpable. There were no funduscopic, mucosal, or cutaneous signs of endocarditis. Musculoskeletal examination revealed diffuse tenderness over the right shoulder joint and the lower back. The hematocrit was 34%, and the white blood cell count was 15,600/mm3 with 83% segmented neutrophils, 10% bands, and 70% lymphocytes. Urinalysis was within normal limits. ESR was 74 mm/h. Serum immunoglobulin levels were within normal limits. The chest radiograph was unremarkable. The patient remained afebrile. Four sets of blood cultures grew S. pneumoniae, serotype 38 (Tennessee Department of Public Health, Nashville, TN; Dr. Barry Gray, University of Alabama School of Medicine, Birmingham, AL). An echocardiogram showed moderate mitral regurgitation, but no vegetations. Intravenous penicillin G, 4 million units every 4 hours, was given for 4 weeks with a rapid resolution of malaise, musculoskeletal symptoms, and chills. Elevated ESR and white blood cell count returned to normal levels. The patient remained free of
92
July 1992 The American Journal of Medicine
Volume 93
symptoms therapy.
4 months
after
the completion
of
COMMENTS Pneumococcal endocarditis is an acute severe illness, resembling acute Staphylococcus aureus endocarditis [l-3]. Pneumococcal pneumonia or sinusitis is the usual source of bacteremic seeding of the cardiac valve [3]. Normal heart valves can be infected, and there is a predilection for aortic valve [ 11. Older male alcoholics constitute the majority of patients reported in the literature [4]. The clinical picture is that of an acutely ill, febrile, often comatose patient with septicemia and purulent meningitis [2]. Rapid destruction of the heart valve results in valvular insufficiency, acute congestive heart failure, and high mortality [l-4]. A subacute presentation of pneumococcal endocarditis has very rarely been described (Robert Austrian, M.D., personal communication). Powderly et al [5] reported two patients with a subacute presentation of pneumococcal endocarditis. The clinical course of our patients was remarkable for the absence of the usual characteristics of pneumococcal endocarditis. When cy-hemolytic streptococci grew from blood cultures, subacute bacterial endocarditis secondary to viridans streptococci was suspected in our patients. Both patients were female, were not alcoholics, and presented with a subacute indolent illness. Neither had a fever, pneumonia, or meningitis. The mitral valve was involved in both cases. Medical therapy alone was successful. Both of our patients were elderly. The clinical presentation of endocarditis in the elderly tends to be more indolent and with fewer symptoms than are reported in younger patients [6]. The frequent absence of a febrile response is well recognized in the elderly patients with infective endocarditis [6-8]. In elderly patients with bacterial endocarditis who do develop fever, the height of the febrile response is diminished compared with younger patients [6]. There is little doubt that both of our patients did, in fact, have pneumococcal endocarditis. The absence of valvular vegetations on transthoracic echocardiography is not unexpected. In several published series, only approximately 50% of patients with bacterial endocarditis had valvular vegetations detected by transthoracic echocardiography [9]. Transesophageal echocardiography has a higher sensitivity for valvular vegetations but was not performed in our patients [lo]. Patients with welldocumented pneumococcal endocarditis and no vegetations on echocardiography have previously been reported [5,11]. Two of seven patients report-
SUBACUTE
ed by Powderly et al [5] and two of five patients reported by Bruyn et al [ll] had no valvular vegetations detected by transthoracic echocardiography. Elderly patients with bacterial endocarditis are less likely to have valvular vegetations detected by echocardiography than younger patients [S]. Pneumococcal bacteremia without an obvious primary focus occurs primarily in asplenic patients and in children less than 2 years old [ 121. Spitalny et al [12] reported three elderly patients with pneumococcal bacteremia without a primary focus. All three had an acute febrile illness, no clinical findings of endocarditis, and a serious underlying disease [12]. The clinical pictures in both of our patients fulfiied the strict clinical criteria for probable endocarditis, as defined by Fordham Von Reyn et al [ 131. The first patient had a total of five out of five sets of blood cultures, obtained over a 72-hour period, positive for S. pneumoniae. She had both auscultatory and echocardiographic evidence of severe mitral regurgitation. Hematuria and abnormal serum BUN and creatinine levels were suggestive of glomerulonephritis. No source of pneumococcal bacteremia, other than the heart, was found. Longstanding clinical and laboratory abnormalities resolved with penicillin G therapy. The second patient had four of four blood cultures positive for S. pneumoniae. Significant mitral regurgitation was found by both auscultation and echocardiography. No extracardiac source of pneumococcal bacteremia was apparent. The clinical and laboratory abnormalities resolved after penicillin G therapy. The majority of reported cases of pneumococcal endocarditis present with an acute, fulminant clinical picture [l-5]. Pneumococcal endocarditis can, however, present with an indolent clinical picture as exemplified by our patients. Such presentation
PNEUMDCDCCAL
ENDGCARDITIS
/ GELFAND
AND THRELKELD
of pneumococcal endocarditis is probably rare, but should be considered in the setting of subacute bacterial endocarditis secondary to a-hemolytic streptococci.
ACKNOWLEDGMENT We are indebted to Drs. Robert Austrian and Ralph Tompsett for their valuable advice and to Mrs. Pat McCullough for assistance in the preparation of the manuscript.
REFERENCES 1. Straus AL, Hamburger
M. Pneumococcal
endocarditis
in the penicillin era.
Arch Intern Med 1966; 118: 190-8. 2. Austrian R. Pneumococcal endocarditis, meningitis, and rupture of the aortic valve. Arch Intern Med 1957; 99: 539-44. 3. Wolff M. Regnier B. Witchitz S, Gilbert C, Amoudry C, Vachon F. Pneumococcal endocarditis. Eur Heart J 1984; 5 Suppl C: 77-80. 4. Buchbinder NA, Roberts WC. Alcoholism; an important but unemphasized factor predisposing to infective endocarditis. Arch Intern Med 1973; 132:
689-92. 5. Powderly WG, Stanley SL. Medoff G. Pneumococcal endocarditis: report of a series and review of the literature. Rev Infect Dis 1986; 8: 786-91. 6. Terpenning MS. Buggy BP, Kauffman CA. infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: 626-34. 7. Robbins N, DeMaria A, Miller MH. Infective endocarditis in the elderly. South Med J 1980; 73: 1335-8. 8. Applefeld MM, Hornick RB. Infective endocarditis in patients over age 60. Am Heart J 1974; 88: 90-4. 9. Steckelberg JM. Murphy JG, Ballard D. eta/. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med 1991; 114: 63640. 10. Mugge A. Daniel WG, Frank G, Lichtlen PR. Echocardiography in infectiie endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach. J Am Coll Cardiol 1989; 14: 631-8. 11. Bruyn GAW. Thompson J. Van Der Meer JWM. Pneumococcal endocarditis in adult patients. A report of five cases and review of the literature. Q J Med
1990; 74: 33-40. 12. Spitalny KC, Bromberg K. Ginsberg MB. Streptococcus pneumoniae bacteremia without an identifiable focus in adults. Johns Hopkins Med J 1982; 150:
36-7. 13. Fordham Von Reyn C, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981; 94: 506-18.
July 1992
The American
Journal
of Medicine
Volume
93
93
