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The recognition of infective endocarditis
ORIGINAL CONTRIBUTION
The Recognition of Infective Endocarditis Mark S. DeManuelle, MD* Gary F. Carroll, MDt Frederick W. Derks, MDt New Orleans, Louisiana
Patients with infective endocarditis are frequently first e v a l u a t e d in an emergency department at a time when clinical data are insufficient for a conclusive diagnosis. The records of 22 patients with proven bacterial endocarditis first seen in our emergency department were reviewed. The most common feature of the initial history was the presence of fever in 11 (50%). The most common physical finding was a heart murmur in 18 (82%). All patients had positive blood cultures. The most frequently isolated organism was Staphylococcus aureus. Pertinent clinical and laboratory data available on admission that enabled the emergency physician to suspect infective endocarditis were systemic manifestations of fever, malaise and arthralgias together with anemia, leukocytosis and hematuria. DeManuelle MS, Carroll GF, Derks FW: The recognition of infective endocarditis. JACEP 8:346-349, September 1979.
endocarditis, infective, recognition of INTRODUCTION
P a t i e n t s w i t h infective endocarditis frequently first come to medical attention in the e m e r g e n c y d e p a r t m e n t . In our i n s t i t u t i o n we have found t h a t a large n u m b e r do not have typical clinical findings and, as a result, diagnosis and t h e r a p y are frequently delayed. This led us to study f e a t u r e s of t h e clinical complex of infective e n d o c a r d i t i s which would help the e m e r g e n c y physician. A high index of suspicion is often p a r a m o u n t in recognizing atypical p r e s e n t a t i o n s of infective endocarditis.1, 2 MATERIALS AND METHODS
P a t i e n t s a t our i n s t i t u t i o n w i t h infective e n d o c a r d i t i s w e r e i d e n t i f i e d through the record l i b r a r y by c o m p u t e r coding for this diagnosis. For 22 patients with this diagnosis, the clinical record (including history, physical e x a m and l a b o r a t o r y data) was reviewed on each p a t i e n t selected. P a t i e n t s were selected because of r a p i d d e t e r i o r a t i o n and morbid complications in order to ill u s t r a t e the frequent absence of f a m i l i a r signs and s y m p t o m s and to e m p h a s i z e the importance of e a r l y diagnosis and t r e a t m e n t . A l t h o u g h we did not select p a t i e n t s because of positive blood cultures, all 22 p a t i e n t s in our study h a d a t least one positive blood culture, t h u s confirming the diagnosis. RESULTS
The incidence of selected features classically associated w i t h infective endocarditis was recorded for 22 p a t i e n t s (Table 1). The most common physical finding was the presence of a h e a r t m u r m u r , u s u a l l y systolic, seen in 18 p a t i e n t s From the Department of Emergency Medicine, .1- Charity Hospital of Louisiana, and the Department of Medicine,t Louisiana State University Medie~,! Center, New Orleans, Louisiana. Address for reprints: Gary F. Carroll, MD, Department of Emergency Medicine, CharitY Hospital of Louisiana, 1532 Tulane Avenue, New Orleans, Louisiana 70140. 8:9 (September) 1979
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Table 1 FEATURES ASSOCIATED WITH INFECTIVE ENDOCARDITIS n=22
No Positive
%
Fever Constitutional symptoms (weakness, anorexia, malaise, weight loss) Arthralgia/myalgia Pleuritic chest pain
11 8
50 36
4 3
18 14
Physical examination
Murmurs Systolic Systolic & diastolic Diastolic Congestive heart failure Pulmonary emboli Mucocutaneous signs Splenomegaly Other embolic phenomena Neurologic deficit
18 14 4 0 10 6 5 2 1 1
Laboratory findings
Leu kocytosis Anemia (Hct. less than 30%) Hematuria (micro) Azotemia
11 9 7 2
82 64 18 0 45 27 23 9 5 5 50 41 .32 9
Source
Finding
Clinical history
Table 2 ISOLATION OF ORGANISMS FROM BLOOD CULTURES n = 22
No
%
Staphylococcus aureus
8
36
Alpha-hemolytic streptococcus (viridans group)
4
18
Streptococcus faecalis
4
18
Candida albicans
2
'9
Beta-hemolytic streptococcus, Group A (pyogenes group)
1
5
Microaerophilic, alpha-hemolytic streptococcus Gamma-hemolytic streptococcus
1
5
1
5
Serratia marcescens
1
5
Organism
(enterococcus)
(82%). Four p a t i e n t s had a diastolic and a systolic m u r m u r . No p a t i e n t had a diastolic m u r m u r alone. Other common findings included fever .in 11 (50%), congestive h e a r t failure in ten (45%), and a n e m i a in n i n e (41%). AIt h o u g h we a r e a w a r e t h a t fever, a n e m i a and/or congestive h e a r t failore c a n c a u s e m u r m u r s or accent u a t e p r e - e x i s t i n g m u r m u r s in the absence of endocarditis, we saw fever
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and m u r m u r combined in 10 (45%) patients and murmur with either a n e m i a or congestive h e a r t failure in n i n e p a t i e n t s (41%). The combination of fever, a n e m i a a n d m u r m u r , the classic t r i a d of endocarditis, was detected in only six (27%) patients. Leukocytosis was present in 11 p a t i e n t s (50%) a n d h e m a t u r i a i n seven (32%). Azotemia was seen in only two (9%) of our patients.
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All 22 p a t i e n t s had one or more positive blood cultures (Table 2). The most common o r g a n i s m was Staphylococcus a u r e u s c u l t u r e d i n 8 pat i e n t s (36%). O t h e r o r g a n i s m s of h i g h v i r u l e n c e were Streptococcus pyogenes in one p a t i e n t (5%), Candida albicans i n two p a t i e n t s (9%), and Serratia marcescens in one pat i e n t (5%). The r e m a i n i n g t e n cases were associated w i t h o r g a n i s m s of relatively low virulence. Pleuritic chest pain was present in three patients (14%). Twelve patients (55%) gave a history of recent illicit i n t r a v e n o u s drug use. Of these 12, t e n had h e a r t m u r m u r s . Eleven of those 12 p a t i e n t s with a history of intravenous drug use underwent echocardiography and/or cardiac catheterization. Eight 0f these 11 pctients had evidence of left-sided endocarditis while only one p a t i e n t had tricuspid involvement. The incidence of congestive h e a r t failure was the same in addict and n o n a d d i c t groups. Mucocutaneous signs were seen i n five p a t i e n t s (23%). P e t e c h i a e were noted in three p a t i e n t s (14%). One p a t i e n t (5%) had a n Osler's node a n d one d e m o n s t r a t e d c l u b b i n g of the fingers (5%). Two of our p a t i e n t s (9%) demo n s t r a t e d splenomegaly. One had b e e n symptomatic t e n weeks a n d the other, for almost six months. Six patients ( 2 7 % ) h a d objective findings of p u l m o n a r y embolization - - i n f i l t r a t e s on c h e s t x-ray films a n d / o r p o s i t i v e p u l m o n a r y angiograms; four of these were addicts. Only one p a t i e n t i n our series (5%) presented with findings suggestive of systemic embolization, and at autopsy was found to have a mycotic a n e u r y s m of the right middle cerebral artery. Six (27%) other patients developed major embolic disease during hospitalization. In our series, a hematocrit reacli n g of less t h a n 30% was recorded in n i n e p a t i e n t s (41%). Five p a t i e n t s (23%) h a d a h e m a t o c r i t of less t h a n 26% and three of these had acute endocarditis with symptomatology for less t h a n four days.
DISCUSSION Infective e n d o c a r d i t i s is ciassically 1-4 associated with bacteremia, fever, cardiac m u r m u r s , splenomegaly, embolic p h e n o m e n a , neurologic and r e n a l manifestations, and various signs of microvascular involvem e n t . A l t h o u g h t h e o n s e t of end o c a r d i t i s is u s u a l l y i n s i d i o u s , it often presents d r a m a t i c a l l y with
8i9 (September) 1979
high fever, p u l m o n a r y edema, major emboli or subarachnoid hemorrhage, especially when associated with virulent .organisms. 2,5 In his review of the c u r r e n t literature, J o h n s o n ~ states t h a t fever is the most common finding in infective endocarditis and is u s u a l l y p r e s e n t at some time d u r i n g the course of the illness. This was borne out in our patients where a t e m p e r a t u r e elevation was ,found i n I1 p a t i e n t s (50%). Of the 12 patients who admitted recent illicit i n t r a v e n o u s drug use, o n l y two c o m p l a i n e d of p l e u r i t i c chest pain. According to C a n n o n and Cobbs, 6 pleuritic chest pain suggesting embolization from a right-sided endocarditis is the a d m i t t i n g comp l a i n t in 30% of addicts. A n isolated systolic m u r m u r was heard in 18 patients (82%). Several of these had a history of a cardiac m u r m u r since childhood; documentation was i n s u f f i c i e n t to determine if the m u r m u r was changed. M u r m u r s are f r e q u e n t l y a b s e n t i n p a t i e n t s w i t h a c u t e e n d o c a r d i t i s , a n d are especially u n c o m m o n i n those with tricuspid valve involvement.7,s The diagnosis of t r i c u s p i d insufficiency m a y be v e r y difficult to e s t a b l i s h w i t h o u t echocardiography or cardiac c a t h e t e r i z a t i o n . 9 O u r f i n d i n g s regarding left-sided endocarditis in addicts are i n a g r e e m e n t with two earlier studiesT, 1° of endocarditis in illicit drug users in which the mitral and/or aortic valves were far more f~equently involved t h a n the tricuspid valve. On the other hand, the recent l i t e r a t u r e indicates t h a t tricuspid i n v o l v e m e n t is being recognized with i n c r e a s i n g frequency. 6,~1,~2 H e a r t f a i l u r e o c c u r s at some t i m e d u r i n g h o s p i t a l i z a t i o n i n at least one t h i r d of addicts w i t h endocarditis, is u s u a l l y associated with left-sided lesions, a n d is the most c o m m o n c a u s e of d e a t h in addicts with endocarditis. 5 Surprisingly, the incidence of congestive heart failure in our study was equal in addict and nonaddict groups. Mucocutaneous signs of infective endocarditis include splinter hemorrhages, clubbing, petechiae, J a n e w a y lesions, a n d Osler's nodes. Petechiae are seen in 20% to 70% of cases of infectious e n d o c a r d i t i s but u s u a l l y occur in p a t i e n t s with prolonged illness and are exacerbated after specific therapy. 2 Petechiae probably represent e x t r a v a s a t i o n of blood associated w i t h a superficial vasculitis. Osler's nodes are also felt to be seco n d a r y to v a s c u l i t i s a n d occur in most series i n 10% to 50% of pa-
8:9 (Septem bet) 1979
tients, the same frequency as clubbing of the digits. 8 Splenomegaly has been observed i n 10% to 60% of p a t i e n t s with infective endocarditis, and is most comm o n i n l o n g - s t a n d i n g disease. 4,13 O n l y two of our p a t i e n t s (9%) dem o n s t r a t e d this finding. Symptoms related to p u l m o n a r y embolic p h e n o m e n a are f r e q u e n t l y the p r e s e n t i n g symptoms in narcotic addicts w i t h infective endocarditis. R e c u r r e n t episodes of ~'pneumonia" in these patients should strongly suggest the possibility of infective endocarditis.5,7, 9 B a n k s and Fletcher ~ noted t h a t 5 2 ~ of addicts i n t h e i r series had septic p u l m o n a r y emboli s i m u l a t i n g pneumonia. In our series of 22 patients, only six (27%) presented with objective findings of p u l m o n a r y e m b o l i z a t i o n ; four of these were narcotic addicts. Major e m b o l i to o r g a n s o t h e r t h a n the l u n g have been recognized i n 35% Of p a t i e n t s with infective endocarditis and are seen with increasing frequency as the disease progresses. 14 Neurologic m a n i f e s t a t i o n s are seen i n 20% to 40% of patients and major cerebral embolization is seen is 10% to 30%. 1~ We saw only one pat i e n t w i t h f i n d i n g s s u g g e s t i v e of cerebral embolization and on autopsy found to have a mycotic aneurysm. Six o t h e r s (27%) developed m a j o r embolic disease d u r i n g hospitalization. Laboratory findings in cases of infective endocarditis are extremely variable d e p e n d i n g on the series rev i e w e d . 16 I n m o s t series,l,13,16 leukocytosis is not a p r o m i n e n t feature and a white blood cell count of 13,000/cu m m or greater is rare ex'cept i n acute e n d o c a r d i t i s . I n our series which included acute or especially severe cases, a white blood cell c o u n t g r e a t e r t h a n 12,000/cu m m was seen in 11 p a t i e n t s (50%). A n e m i a has b e e n r e g a r d e d as one of t h e c l a s s i c f i n d i n g s i n endocarditis, especially if the disease has been of long duration. 17 The severe a n e m i a in our series could not be explained by other causes and we speculate t h a t the pathogenesis must i n c l u d e c o n s i d e r a b l e h e m o l y s i s as well as marrow suppression. H e m a t u r i a is a frequent finding in infective endocarditis. It h a s been reported 13 in up to 50% of cases and is due to embolic p h e n o m e n a involving the k i d n e y a n d / o ~ a glomerulitis of a n immune-cofi~plex n a t u r e . H e m a t u r i a was seen in seven of our p a t i e n t s (32%) a n d was most sign i f i c a n t in t h o s e p a t i e n t s w i t h a
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c o m p l i c a t e d course a n d / o r a f a t a l outcome. In general, most cases of infective e n d o c a r d i t i s of a s u b a c u t e or chronic n a t u r e are associated with n o n v i r u l e n t organisms, p a r t i c u l a r l y the a l p h a - h e m o l y t i c streptococcus ( v i r i d a n s group) and e n t e r o c o c c u s (Streptococcus faecalis).4,13,17 Occasionally, micro-aerophilic, alphahemolytic streptococci and nonh e m o l y t i c (or g a m m a - h e m o l y t i c ) streptococci as well as other members of Group D (besides enterococcus) are involved. 4,13 On the other hand, acute cases of infective endocarditis (including patients w i t h history of illicit i n t r a v e n ous drug use as well as those fulmina n t cases not associated with drug usage) are generally associated with v i r u l e n t organisms.4,6,7,1°-12 In most series, S aureus is thee organism most frequently isolated from drug users with infective endocarditis.~,7,1°-~2 In recent years, Candida albicans has emerged as a p r o m i n e n t cause of infective endocarditis in drug users. 4 In o u r s e r i e s , w h i c h i n c l u d e d only acute or f u l m i n a n t cases of infective e n d o c a r d i t i s , S aureus was most f r e q u e n t l y isolated (eight pat i e n t s or 35%) and seven of the eight cases of staphylococcal endocarditis were seen in drug users. Eight of our cases (36%) were associated with relatively n o n v i r u l e n t organisms and C a n d i d a albicans was c u l t u r e d in two patients. In c o n t r a s t to some reports of a high percentage of negative blood c u l t u r e s , up to 28% in some series,l~, is all of our 22 patients had at least one positive blood culture. A l t h o u g h t h i s is a r e t r o s p e c t i v e study, our p a t i e n t s were identified by computer coding for a diagnosis of infective endocarditis and selected for rapid deterioration and morbid complications. They were not selected for positive blood cultures. Perhaps the high percentage of positive blood cult u r e s in our series is due not only to the q u a l i t y of our clinical microbiology laboratory, which is e x t r e m e l y m e t i c u l o u s in the processing of all blood cultures, b u t also to the high index of suspicion m a i n t a i n e d at our i n s t i t u t i o n . Multiple blood cultures from various sites are obtained in all drug users admitted to the hospital with a suspected diagnosis of infective endocarditis.
CONCLUSION Many patients with infective endocarditis lack the classical clinical features u s u a l l y associated with dis-
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ease, e s p e c i a l l y w h e n t h e y p r e s e n t i n a n a c u t e or f u l m i n a n t m a n n e r . O u r s e r i e s d e s c r i b e s t h e p r e s e n t a t i o n s of 22 p a t i e n t s e v e n t u a l l y d i a g n o s e d as having infective endocarditis. The v a r i e t y of p r e s e n t a t i o n s d e m a n d s a h i g h i n d e x of s u s p i c i o n to r e c o g n i z e t h e s e cases.
E n d o c a r d i t i s . N e w York, G r u n e a n d Stratton, Inc, 1978, pp 125-148.
endocarditis in heroin addicts. A m J Med 55:444-451, 1973.
4. Lerner PI, Weinstein L: Infective endocarditis in the antibiotic era. N Engl J Med 274:259-266, 388-393, 1966.
12. Menda KB, Gorbach KL: Major medical complications of heroin addicts. A n n Intern Med 78:25-32, 1973.
5. Curtis J, Richman BL, Feinstein MA: Infective endocarditis in narcotic addicts. South Med J 67:4-9, 1974.
13. B l u m e r G: S u b a c u t e b a c t e r i a l endocarditis. Medicine 2:105-170, 1923.
The authors wish to express t h e i r gratw itude to Harry E. Dascomb, MD, of the D e p a r t m e n t of Medicine, Louisiana State University Medical Center, for his con~ tributions in p r e p a r a t i o n of t h i s manuscript and also to Ms. S a r a h Robinson for her technical assistance.
6. C a n n o n NJ, Cobbs G: Infective endocarditis in drug addicts, in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 111-127.
REFERENCES 1. J o h n s o n WD J r : T h e c l i n i c a l syndrome, in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 87-100. 2. Weinstein L, Rubin RH: Infective endocarditis. Prog Cardiovasc Dis 16:239302, 1973. 3. McAnulty JH, Rahimtoola SH, DeMots H, et al: Clinical features of infective endocarditis. Rahimtoola SH (ed): Infective
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7. Ramsey RG, G u n n a r RM, Tobin J R Jr: Endocarditis in the drug addict. A m J Cardiol 25:608-618, 1970. 8. MacGregor GA: Murmurless bacterial endocarditis. Br Med J 1:1011-1013, 1956. 9. Stimmel B, Dack S: Infective endocarditis in narcotic addicts, in Rahimtoola SH (ed): I n f e c t i v e E n d o c a r d i t i s . New York, Grune and Stratton, 1978, pp 195209. 10. C h e r u b i n CE, Baden M, Kavaler F, et al: Infective e n d o c a r d i t i s in h e r o i n addicts. A n n I n t e r n M e d 69:1091-1098, 1968. 11. Banks T, Fletcher R, Ali N: Infective
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14. Weinstein L, Schlesinger JJ: Pathoanatomic, pathophysiologic and chemical c o r r e l a t i o n s in endocarditis. N E n g l J Med 291:832-837, 1122-1126, 1974. 15. J o n e s JR, S i e k e r t RH, Geraci JE: Neurologic m a n i f e s t a t i o n s of b a c t e r i a l endocarditis. A n n Intern Med !7:21-28, 1969. 16. Mendell GL: The laboratory in diagnosis and m a n a g e m e n t , in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 155-156. 17. Mendell GL, Kaye D, Levison ME, et al: Enterecoccal endocarditis: A n analysis of 38 patients observed at the New York Hospital - - Cornell Medical Center. Arch Intern Med 125:258-264, 1975. 18. Louria DB, Stiff DP, B e n n e t t R: Dis. s e m i n a t e d m o n i l i a s i s in t h e adult. Medicine 41:307-337, 1962.
8.9 (September) 1979
The Recognition of Infective Endocarditis Mark S. DeManuelle, MD* Gary F. Carroll, MDt Frederick W. Derks, MDt New Orleans, Louisiana
Patients with infective endocarditis are frequently first e v a l u a t e d in an emergency department at a time when clinical data are insufficient for a conclusive diagnosis. The records of 22 patients with proven bacterial endocarditis first seen in our emergency department were reviewed. The most common feature of the initial history was the presence of fever in 11 (50%). The most common physical finding was a heart murmur in 18 (82%). All patients had positive blood cultures. The most frequently isolated organism was Staphylococcus aureus. Pertinent clinical and laboratory data available on admission that enabled the emergency physician to suspect infective endocarditis were systemic manifestations of fever, malaise and arthralgias together with anemia, leukocytosis and hematuria. DeManuelle MS, Carroll GF, Derks FW: The recognition of infective endocarditis. JACEP 8:346-349, September 1979.
endocarditis, infective, recognition of INTRODUCTION
P a t i e n t s w i t h infective endocarditis frequently first come to medical attention in the e m e r g e n c y d e p a r t m e n t . In our i n s t i t u t i o n we have found t h a t a large n u m b e r do not have typical clinical findings and, as a result, diagnosis and t h e r a p y are frequently delayed. This led us to study f e a t u r e s of t h e clinical complex of infective e n d o c a r d i t i s which would help the e m e r g e n c y physician. A high index of suspicion is often p a r a m o u n t in recognizing atypical p r e s e n t a t i o n s of infective endocarditis.1, 2 MATERIALS AND METHODS
P a t i e n t s a t our i n s t i t u t i o n w i t h infective e n d o c a r d i t i s w e r e i d e n t i f i e d through the record l i b r a r y by c o m p u t e r coding for this diagnosis. For 22 patients with this diagnosis, the clinical record (including history, physical e x a m and l a b o r a t o r y data) was reviewed on each p a t i e n t selected. P a t i e n t s were selected because of r a p i d d e t e r i o r a t i o n and morbid complications in order to ill u s t r a t e the frequent absence of f a m i l i a r signs and s y m p t o m s and to e m p h a s i z e the importance of e a r l y diagnosis and t r e a t m e n t . A l t h o u g h we did not select p a t i e n t s because of positive blood cultures, all 22 p a t i e n t s in our study h a d a t least one positive blood culture, t h u s confirming the diagnosis. RESULTS
The incidence of selected features classically associated w i t h infective endocarditis was recorded for 22 p a t i e n t s (Table 1). The most common physical finding was the presence of a h e a r t m u r m u r , u s u a l l y systolic, seen in 18 p a t i e n t s From the Department of Emergency Medicine, .1- Charity Hospital of Louisiana, and the Department of Medicine,t Louisiana State University Medie~,! Center, New Orleans, Louisiana. Address for reprints: Gary F. Carroll, MD, Department of Emergency Medicine, CharitY Hospital of Louisiana, 1532 Tulane Avenue, New Orleans, Louisiana 70140. 8:9 (September) 1979
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Table 1 FEATURES ASSOCIATED WITH INFECTIVE ENDOCARDITIS n=22
No Positive
%
Fever Constitutional symptoms (weakness, anorexia, malaise, weight loss) Arthralgia/myalgia Pleuritic chest pain
11 8
50 36
4 3
18 14
Physical examination
Murmurs Systolic Systolic & diastolic Diastolic Congestive heart failure Pulmonary emboli Mucocutaneous signs Splenomegaly Other embolic phenomena Neurologic deficit
18 14 4 0 10 6 5 2 1 1
Laboratory findings
Leu kocytosis Anemia (Hct. less than 30%) Hematuria (micro) Azotemia
11 9 7 2
82 64 18 0 45 27 23 9 5 5 50 41 .32 9
Source
Finding
Clinical history
Table 2 ISOLATION OF ORGANISMS FROM BLOOD CULTURES n = 22
No
%
Staphylococcus aureus
8
36
Alpha-hemolytic streptococcus (viridans group)
4
18
Streptococcus faecalis
4
18
Candida albicans
2
'9
Beta-hemolytic streptococcus, Group A (pyogenes group)
1
5
Microaerophilic, alpha-hemolytic streptococcus Gamma-hemolytic streptococcus
1
5
1
5
Serratia marcescens
1
5
Organism
(enterococcus)
(82%). Four p a t i e n t s had a diastolic and a systolic m u r m u r . No p a t i e n t had a diastolic m u r m u r alone. Other common findings included fever .in 11 (50%), congestive h e a r t failure in ten (45%), and a n e m i a in n i n e (41%). AIt h o u g h we a r e a w a r e t h a t fever, a n e m i a and/or congestive h e a r t failore c a n c a u s e m u r m u r s or accent u a t e p r e - e x i s t i n g m u r m u r s in the absence of endocarditis, we saw fever
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and m u r m u r combined in 10 (45%) patients and murmur with either a n e m i a or congestive h e a r t failure in n i n e p a t i e n t s (41%). The combination of fever, a n e m i a a n d m u r m u r , the classic t r i a d of endocarditis, was detected in only six (27%) patients. Leukocytosis was present in 11 p a t i e n t s (50%) a n d h e m a t u r i a i n seven (32%). Azotemia was seen in only two (9%) of our patients.
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All 22 p a t i e n t s had one or more positive blood cultures (Table 2). The most common o r g a n i s m was Staphylococcus a u r e u s c u l t u r e d i n 8 pat i e n t s (36%). O t h e r o r g a n i s m s of h i g h v i r u l e n c e were Streptococcus pyogenes in one p a t i e n t (5%), Candida albicans i n two p a t i e n t s (9%), and Serratia marcescens in one pat i e n t (5%). The r e m a i n i n g t e n cases were associated w i t h o r g a n i s m s of relatively low virulence. Pleuritic chest pain was present in three patients (14%). Twelve patients (55%) gave a history of recent illicit i n t r a v e n o u s drug use. Of these 12, t e n had h e a r t m u r m u r s . Eleven of those 12 p a t i e n t s with a history of intravenous drug use underwent echocardiography and/or cardiac catheterization. Eight 0f these 11 pctients had evidence of left-sided endocarditis while only one p a t i e n t had tricuspid involvement. The incidence of congestive h e a r t failure was the same in addict and n o n a d d i c t groups. Mucocutaneous signs were seen i n five p a t i e n t s (23%). P e t e c h i a e were noted in three p a t i e n t s (14%). One p a t i e n t (5%) had a n Osler's node a n d one d e m o n s t r a t e d c l u b b i n g of the fingers (5%). Two of our p a t i e n t s (9%) demo n s t r a t e d splenomegaly. One had b e e n symptomatic t e n weeks a n d the other, for almost six months. Six patients ( 2 7 % ) h a d objective findings of p u l m o n a r y embolization - - i n f i l t r a t e s on c h e s t x-ray films a n d / o r p o s i t i v e p u l m o n a r y angiograms; four of these were addicts. Only one p a t i e n t i n our series (5%) presented with findings suggestive of systemic embolization, and at autopsy was found to have a mycotic a n e u r y s m of the right middle cerebral artery. Six (27%) other patients developed major embolic disease during hospitalization. In our series, a hematocrit reacli n g of less t h a n 30% was recorded in n i n e p a t i e n t s (41%). Five p a t i e n t s (23%) h a d a h e m a t o c r i t of less t h a n 26% and three of these had acute endocarditis with symptomatology for less t h a n four days.
DISCUSSION Infective e n d o c a r d i t i s is ciassically 1-4 associated with bacteremia, fever, cardiac m u r m u r s , splenomegaly, embolic p h e n o m e n a , neurologic and r e n a l manifestations, and various signs of microvascular involvem e n t . A l t h o u g h t h e o n s e t of end o c a r d i t i s is u s u a l l y i n s i d i o u s , it often presents d r a m a t i c a l l y with
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high fever, p u l m o n a r y edema, major emboli or subarachnoid hemorrhage, especially when associated with virulent .organisms. 2,5 In his review of the c u r r e n t literature, J o h n s o n ~ states t h a t fever is the most common finding in infective endocarditis and is u s u a l l y p r e s e n t at some time d u r i n g the course of the illness. This was borne out in our patients where a t e m p e r a t u r e elevation was ,found i n I1 p a t i e n t s (50%). Of the 12 patients who admitted recent illicit i n t r a v e n o u s drug use, o n l y two c o m p l a i n e d of p l e u r i t i c chest pain. According to C a n n o n and Cobbs, 6 pleuritic chest pain suggesting embolization from a right-sided endocarditis is the a d m i t t i n g comp l a i n t in 30% of addicts. A n isolated systolic m u r m u r was heard in 18 patients (82%). Several of these had a history of a cardiac m u r m u r since childhood; documentation was i n s u f f i c i e n t to determine if the m u r m u r was changed. M u r m u r s are f r e q u e n t l y a b s e n t i n p a t i e n t s w i t h a c u t e e n d o c a r d i t i s , a n d are especially u n c o m m o n i n those with tricuspid valve involvement.7,s The diagnosis of t r i c u s p i d insufficiency m a y be v e r y difficult to e s t a b l i s h w i t h o u t echocardiography or cardiac c a t h e t e r i z a t i o n . 9 O u r f i n d i n g s regarding left-sided endocarditis in addicts are i n a g r e e m e n t with two earlier studiesT, 1° of endocarditis in illicit drug users in which the mitral and/or aortic valves were far more f~equently involved t h a n the tricuspid valve. On the other hand, the recent l i t e r a t u r e indicates t h a t tricuspid i n v o l v e m e n t is being recognized with i n c r e a s i n g frequency. 6,~1,~2 H e a r t f a i l u r e o c c u r s at some t i m e d u r i n g h o s p i t a l i z a t i o n i n at least one t h i r d of addicts w i t h endocarditis, is u s u a l l y associated with left-sided lesions, a n d is the most c o m m o n c a u s e of d e a t h in addicts with endocarditis. 5 Surprisingly, the incidence of congestive heart failure in our study was equal in addict and nonaddict groups. Mucocutaneous signs of infective endocarditis include splinter hemorrhages, clubbing, petechiae, J a n e w a y lesions, a n d Osler's nodes. Petechiae are seen in 20% to 70% of cases of infectious e n d o c a r d i t i s but u s u a l l y occur in p a t i e n t s with prolonged illness and are exacerbated after specific therapy. 2 Petechiae probably represent e x t r a v a s a t i o n of blood associated w i t h a superficial vasculitis. Osler's nodes are also felt to be seco n d a r y to v a s c u l i t i s a n d occur in most series i n 10% to 50% of pa-
8:9 (Septem bet) 1979
tients, the same frequency as clubbing of the digits. 8 Splenomegaly has been observed i n 10% to 60% of p a t i e n t s with infective endocarditis, and is most comm o n i n l o n g - s t a n d i n g disease. 4,13 O n l y two of our p a t i e n t s (9%) dem o n s t r a t e d this finding. Symptoms related to p u l m o n a r y embolic p h e n o m e n a are f r e q u e n t l y the p r e s e n t i n g symptoms in narcotic addicts w i t h infective endocarditis. R e c u r r e n t episodes of ~'pneumonia" in these patients should strongly suggest the possibility of infective endocarditis.5,7, 9 B a n k s and Fletcher ~ noted t h a t 5 2 ~ of addicts i n t h e i r series had septic p u l m o n a r y emboli s i m u l a t i n g pneumonia. In our series of 22 patients, only six (27%) presented with objective findings of p u l m o n a r y e m b o l i z a t i o n ; four of these were narcotic addicts. Major e m b o l i to o r g a n s o t h e r t h a n the l u n g have been recognized i n 35% Of p a t i e n t s with infective endocarditis and are seen with increasing frequency as the disease progresses. 14 Neurologic m a n i f e s t a t i o n s are seen i n 20% to 40% of patients and major cerebral embolization is seen is 10% to 30%. 1~ We saw only one pat i e n t w i t h f i n d i n g s s u g g e s t i v e of cerebral embolization and on autopsy found to have a mycotic aneurysm. Six o t h e r s (27%) developed m a j o r embolic disease d u r i n g hospitalization. Laboratory findings in cases of infective endocarditis are extremely variable d e p e n d i n g on the series rev i e w e d . 16 I n m o s t series,l,13,16 leukocytosis is not a p r o m i n e n t feature and a white blood cell count of 13,000/cu m m or greater is rare ex'cept i n acute e n d o c a r d i t i s . I n our series which included acute or especially severe cases, a white blood cell c o u n t g r e a t e r t h a n 12,000/cu m m was seen in 11 p a t i e n t s (50%). A n e m i a has b e e n r e g a r d e d as one of t h e c l a s s i c f i n d i n g s i n endocarditis, especially if the disease has been of long duration. 17 The severe a n e m i a in our series could not be explained by other causes and we speculate t h a t the pathogenesis must i n c l u d e c o n s i d e r a b l e h e m o l y s i s as well as marrow suppression. H e m a t u r i a is a frequent finding in infective endocarditis. It h a s been reported 13 in up to 50% of cases and is due to embolic p h e n o m e n a involving the k i d n e y a n d / o ~ a glomerulitis of a n immune-cofi~plex n a t u r e . H e m a t u r i a was seen in seven of our p a t i e n t s (32%) a n d was most sign i f i c a n t in t h o s e p a t i e n t s w i t h a
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c o m p l i c a t e d course a n d / o r a f a t a l outcome. In general, most cases of infective e n d o c a r d i t i s of a s u b a c u t e or chronic n a t u r e are associated with n o n v i r u l e n t organisms, p a r t i c u l a r l y the a l p h a - h e m o l y t i c streptococcus ( v i r i d a n s group) and e n t e r o c o c c u s (Streptococcus faecalis).4,13,17 Occasionally, micro-aerophilic, alphahemolytic streptococci and nonh e m o l y t i c (or g a m m a - h e m o l y t i c ) streptococci as well as other members of Group D (besides enterococcus) are involved. 4,13 On the other hand, acute cases of infective endocarditis (including patients w i t h history of illicit i n t r a v e n ous drug use as well as those fulmina n t cases not associated with drug usage) are generally associated with v i r u l e n t organisms.4,6,7,1°-12 In most series, S aureus is thee organism most frequently isolated from drug users with infective endocarditis.~,7,1°-~2 In recent years, Candida albicans has emerged as a p r o m i n e n t cause of infective endocarditis in drug users. 4 In o u r s e r i e s , w h i c h i n c l u d e d only acute or f u l m i n a n t cases of infective e n d o c a r d i t i s , S aureus was most f r e q u e n t l y isolated (eight pat i e n t s or 35%) and seven of the eight cases of staphylococcal endocarditis were seen in drug users. Eight of our cases (36%) were associated with relatively n o n v i r u l e n t organisms and C a n d i d a albicans was c u l t u r e d in two patients. In c o n t r a s t to some reports of a high percentage of negative blood c u l t u r e s , up to 28% in some series,l~, is all of our 22 patients had at least one positive blood culture. A l t h o u g h t h i s is a r e t r o s p e c t i v e study, our p a t i e n t s were identified by computer coding for a diagnosis of infective endocarditis and selected for rapid deterioration and morbid complications. They were not selected for positive blood cultures. Perhaps the high percentage of positive blood cult u r e s in our series is due not only to the q u a l i t y of our clinical microbiology laboratory, which is e x t r e m e l y m e t i c u l o u s in the processing of all blood cultures, b u t also to the high index of suspicion m a i n t a i n e d at our i n s t i t u t i o n . Multiple blood cultures from various sites are obtained in all drug users admitted to the hospital with a suspected diagnosis of infective endocarditis.
CONCLUSION Many patients with infective endocarditis lack the classical clinical features u s u a l l y associated with dis-
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ease, e s p e c i a l l y w h e n t h e y p r e s e n t i n a n a c u t e or f u l m i n a n t m a n n e r . O u r s e r i e s d e s c r i b e s t h e p r e s e n t a t i o n s of 22 p a t i e n t s e v e n t u a l l y d i a g n o s e d as having infective endocarditis. The v a r i e t y of p r e s e n t a t i o n s d e m a n d s a h i g h i n d e x of s u s p i c i o n to r e c o g n i z e t h e s e cases.
E n d o c a r d i t i s . N e w York, G r u n e a n d Stratton, Inc, 1978, pp 125-148.
endocarditis in heroin addicts. A m J Med 55:444-451, 1973.
4. Lerner PI, Weinstein L: Infective endocarditis in the antibiotic era. N Engl J Med 274:259-266, 388-393, 1966.
12. Menda KB, Gorbach KL: Major medical complications of heroin addicts. A n n Intern Med 78:25-32, 1973.
5. Curtis J, Richman BL, Feinstein MA: Infective endocarditis in narcotic addicts. South Med J 67:4-9, 1974.
13. B l u m e r G: S u b a c u t e b a c t e r i a l endocarditis. Medicine 2:105-170, 1923.
The authors wish to express t h e i r gratw itude to Harry E. Dascomb, MD, of the D e p a r t m e n t of Medicine, Louisiana State University Medical Center, for his con~ tributions in p r e p a r a t i o n of t h i s manuscript and also to Ms. S a r a h Robinson for her technical assistance.
6. C a n n o n NJ, Cobbs G: Infective endocarditis in drug addicts, in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 111-127.
REFERENCES 1. J o h n s o n WD J r : T h e c l i n i c a l syndrome, in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 87-100. 2. Weinstein L, Rubin RH: Infective endocarditis. Prog Cardiovasc Dis 16:239302, 1973. 3. McAnulty JH, Rahimtoola SH, DeMots H, et al: Clinical features of infective endocarditis. Rahimtoola SH (ed): Infective
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7. Ramsey RG, G u n n a r RM, Tobin J R Jr: Endocarditis in the drug addict. A m J Cardiol 25:608-618, 1970. 8. MacGregor GA: Murmurless bacterial endocarditis. Br Med J 1:1011-1013, 1956. 9. Stimmel B, Dack S: Infective endocarditis in narcotic addicts, in Rahimtoola SH (ed): I n f e c t i v e E n d o c a r d i t i s . New York, Grune and Stratton, 1978, pp 195209. 10. C h e r u b i n CE, Baden M, Kavaler F, et al: Infective e n d o c a r d i t i s in h e r o i n addicts. A n n I n t e r n M e d 69:1091-1098, 1968. 11. Banks T, Fletcher R, Ali N: Infective
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14. Weinstein L, Schlesinger JJ: Pathoanatomic, pathophysiologic and chemical c o r r e l a t i o n s in endocarditis. N E n g l J Med 291:832-837, 1122-1126, 1974. 15. J o n e s JR, S i e k e r t RH, Geraci JE: Neurologic m a n i f e s t a t i o n s of b a c t e r i a l endocarditis. A n n Intern Med !7:21-28, 1969. 16. Mendell GL: The laboratory in diagnosis and m a n a g e m e n t , in Kaye D (ed): Infective Endocarditis. Baltimore, University P a r k Press, 1976, pp 155-156. 17. Mendell GL, Kaye D, Levison ME, et al: Enterecoccal endocarditis: A n analysis of 38 patients observed at the New York Hospital - - Cornell Medical Center. Arch Intern Med 125:258-264, 1975. 18. Louria DB, Stiff DP, B e n n e t t R: Dis. s e m i n a t e d m o n i l i a s i s in t h e adult. Medicine 41:307-337, 1962.
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