Native valve Staphylococcus epidermidis endocarditis: Report of seven cases and review of the literature

Native Valve staphylococcus epidermidis Endocarditis: Report of Seven Cases and Review of the Literature NADIRARBER,M.D., Petah TikvaandTelAviv, Israel, ARIEMILITIANU, M.D., Technion Haifa, Israel, ARIE BEN-YEHUDA,M.D., Jerusalem, Israel, NORBERTOKRIVOY,M.D., Technion Haifa, Israel, JACKPINKHAS,M.D., YECHEZKELSIDI, M.D., Petah Tikvaand TelAviv, lsrael

This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermkIis. The literature on endocarditis caused by S. epidermiiais is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and shin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis.

is the most comS mon organism isolated from patients with prosthetic valve endocarditis, especially in the periopertaphylococcus

ative period [1,2]. Although previous series have suggested that S. epidermidis causes 1% to 3% of all cases of endocarditis, specific reports of this entity have appeared only rarely. Another review has suggested that this organism causes native valve endocarditis infrequently [3]. The clinical and laboratory features of native valve endocarditis due to S. epidermidis have not been well characterized. We describe seven patients with native valve endocarditis due to S. epidermidis and review the literature with respect to S. epidermidis native valve endocarditis.

CASE REPORTS Patient 1 A 77-year-old man was admitted to our hospital because of weakness and weight loss. Anterolateral myocardial infarction complicated by mitral regurgitation had been diagnosed 5 years previously. He had lost 5 kg in the 2 months prior to presentation but had no gastrointestinal complaints. Upon examination, the patient appeared malnourished, his blood pressure was 120/60 mm Hg, his pulse rate was 80/minute, and his maximal temperature was 366°C on repeated examinations. A grade 216 systolic murmur was heard at the cardiac apex, radiating to the axilla. The rest of the physical examination was normal. S. epidermidis grew in eight blood cultures and in a bone marrow culture. Echocardiography demonstrated a nonrheumatic mitral regurgitation with a possible vegetation on the anterior leaflet. Cloxacillin, 2 g four times daily, was administered for 6 weeks, which resulted in a rapid improvement in the patient’s general condition and in a weight gain. Echocardiography, repeated after 8 weeks, revealed no vegetations. An additional six blood cultures yielded negative results. The patient is still well 2 years later.

From the Departments of Medicine D, Beilinson Medical Center (NA, JP. YS). Petah Tikva, Israel, and the Sackler School of Medicine (NA. JP. YS). Tel Aviv University, Tel Aviv, Israel, the Department of Medicine A (AM, NK), Rambam Medical Center, Faculty of Medicine, Technion Haifa, Israel, and the Department of Medicine A (ABY), Hadassah University Hospital, Jerusalem, Israel. Requests for reprints should be addressed to Yechezkel Sidi, M.D., Department of Medicine ‘D’, Beilinson Medical Center, 49 100 Petah Tikva, Israel. Manuscript submitted June 19, 1990, and accepted in revised form October 1. 1990.

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Patient 2 A 69-year-old man with non-insulin-dependent diabetes mellitus was admitted with fever of 4 days’ duration. He was treated with erythromycin, which 90

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resulted in rapid improvement. On physical examination, he was found to have a temperature of 39.6”C. A grade 216 systolic murmur was heard at the base of the heart. The remainder of the physical examination was within normal limits. Echocardiography was normal, but four blood cultures yielded 5’. epidermidis. Treatment with erythromycin 2.4 g/day and trimethoprim/sulfamethoxazole 44 ml/day was started intravenously. Therapy was changed to gentamicin and cefamezin for an additional 4 weeks, on the basis of culture sensitivity findings. Thereafter, a gradual improvement was observed. The patient was readmitted 3 months later due to fever and progressive heart failure. Aortic insufficiency was diagnosed and the aortic valve was replaced. Histologic examination revealed a fibrotic, calcified valve with a few foci of necrosis and neutrophilic infiltrates. Culture of the resected valve was negative. The patient is still well 3 years later. Patient 3 A 76-year-old man was admitted for investigation of peripheral edema. Mitral valve regurgitation had been diagnosed 3 years prior to admission. Physical examination revealed a pale tachypneic patient with a blood pressure of 140/90 mm Hg and a regular pulse rate of 80/minute. A holosystolic apical murmur 216 compatible with mitral regurgitation was heard. Severe bilateral leg edema was present. No signs of systemic emboli were found. Ten blood cultures grew methicillin-resistant S. epidermidis. Two-dimensional echocardiographic examination showed a small vegetation on the posterior leaflet of the mitral valve. He was treated for 37 days with rifampicin 900 mg/day and vancomycin 0.5 g twice a day, with marked improvement. During 2 years of follow-up, the patient has been free of symptoms. Patient 4 A 67-year-old woman was admitted for investigation of several episodes of fainting in the week prior to admission. Past history revealed aortic stenosis and insufficiency known since 1972, mild renal insufficiency, and recurrent episodes of left ventricular failure in the last year. Physical examination revealed signs of left ventricular failure. Blood pressure was 150/90 mm Hg and the pulse rate was regular at loo/minute. Peripheral emboli were not found. The heart was enlarged with 2/6 diastolic and 316 systolic murmurs on the heart base, compatible with aortic stenosis and insufficiency. Clubbing of the fingernails was observed. Methicillinsensitive S. epidermidis was recovered in two blood cultures. A two-dimensional echocardiographic examination failed to demonstrate vegetations but

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confirmed the diagnosis of aortic stenosis and insufficiency. The patient was treated for 33 days with cloxacillin 8 g/day and rifampicin 900 mg/day. The patient died 6 months later due to acute left ventricular failure. Permission for autopsy was not granted. Patient 5 A 7%year-old man was admitted to neurosurgery for the investigation of sudden progressive quadriparesis with severe neck pain. Four years before admission, he had undergone an aortocoronary bypass; since then, he had had chronic osteomyelitis of the sternum, which was treated periodically with cloxacillin. On this admission, an urgent myelography and computed tomography demonstrated a spinal cord compression in C5-Tl. The patient underwent emergency laminectomy for decompression, but no spinal lesion was found. He developed fever and methicillin-sensitive S. epidermidis was recovered in four blood cultures. His blood pressure was 160/70 mm Hg, with a regular pulse rate of 98,’ minute. Temperature was 37.9”C. A mitral systolic murmur 216 was heard in the left sternal border. A septic embolus (confirmed by biopsy) was found on the right maleolus. A two-dimensional echocardiographic examination showed a small vegetation on the aortic valve with aortic insufficiency and septal hypokinesis. The patient was treated for 30 days with intravenous pefloxacin 400 mg twice a day. After 8 weeks, blood cultures were negative. The patient is well 30 months later. Patient 6 An 82-year-old man was admitted because of fever of 8 weeks’ duration. Three months earlier, retropubic prostatectomy had been performed because of benign hypertrophy of the prostate. A month later, anorexia and weakness appeared, and his temperature was 38°C. The fever was remittent and lasted until the present hospitalization. The patient was known to have mild stable angina pectoris, and aortic incompetence had been diagnosed 5 years earlier by echocardiography. On admission, the physical examination showed a blood pressure of 150/70 mm Hg and a pulse rate of 60/minute. The cardiac apex was palpated in the fifth intercostal space at the anterior axillary line. A third heart sound and a 216 diastolic murmur were heard over the left sternal border. The spleen and liver were not enlarged. Two splinter hemorrhages were found in the right second and third nail beds. The fundi appeared normal. Echocardiography revealed moderate aortic valve incompetence with good left ventricular function and no vegetations. The results of the urinalyJune

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TABLEI Presenting Symptoms of Native Valve Staphyococcus epidermldis Endocarditis

Reference

Number of Patients

[lOI

15

[Ill

3

[I21

21

[131

8

[I41

1

[I51

15

[161

2

H71

2

[la1

2

[W

2

Fw

1

WI

5

1221

1

Our Patients

7

Male/ Mean Female Age 12/3 (80%)

40

o/3 (0%)

47

17/4 (81%)

53

6/Z (75%)

53

l/O (100%)

63

13/Z (87%)

50

l/l (50%)

69

2/o (100%)

29

2/o

53

Fever 15 (100%)

Anorexia/ Weight Weakness Loss

Arthralgia

Emboli

Skin Man- Splenoifestation megaly

NM NM

16 (76%)

NM

(s78%)

;25%)

NM

NM

(:3%)

fZO%)

(47%)

l33%)

;33%)

f33%)

NM

NM

NM NM

(524%)

(533%)

fl3%)

NM

NM

NM

:14%)

f38%)

9 (43%)

(113%)

(113%)

ilOO%)

ilOO%)

NM ?38%)

f33%)

(113%)

(to%)

NM

NM

NM

NM

ilOO%) NM

NM

NM

NM

(690%) 1 (50%)

fsO%)

NM

(fOO%)

:100%)

NM

?40%)

F53%)

fl3%)

?13%)

NM

NM

NM

NM

tsO%)

FlOO%)

flOO%)

NM

NM

;50%) NM

NM

NM $OO%)

NM

NM

NM

NM

(fOO%) 23

l/O (100%)

27

3/Z (60%)

40

O/l (0%)

43

512 (70%)

73

Valve Replacement NM

?40%)

(fOO%)

2/O (100%)

CHF

NM

NM

NM

NM

fiOO%)

flOO%)

$%)

coo%,

NM

NM

NM

NM

?lOO%)

FlOO%)

NM

NM

NM

PO%)

yen,

FO%)

NM

NM

(fOO%) (1100%) (FOO%)

$%) NM

$30%)

1 (100%)

tloo%)

4 (57%)

(457%)

(7;:)

(52%)

FO%)

NM i100%)

fiOO%)

(IlOO%)

YO%)

0 (0%)

FO%)

(233%)

COO%)

;16%)

:33%)

r)o%)

(457%)

;16%)

41%

19%

25%

37%

31%

31%

27%

85 iF = congestive heart failure; NM = not mentioned.

sis were normal and sterile. Four of six blood cultures taken during the first 48 hours of the patient’s stay in the hospital were positive for S. epidermidis. Vancomycin, 1 g twice a day, was started, in light of the culture sensitivities. The antibiotic treatment was given for 6 weeks with a good response and disappearance of the fever during the second week. Three years later, the patient is well. Patient 7 A 72-year-old woman was admitted due to fever (38%) and dyspnea of 3 weeks’ duration. Four years previously, a diagnosis of moderate mitral stenosis had been made by echocardiography. Physical examination, on admission, revealed an irregular rhythm pulse of 84/minute, with a blood pressure of 120/70 mm Hg. The cardiac apex was 760

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tapping with a prominent first heart sound on auscultation. A 3/6 rumbling diastolic murmur was heard immediately after an opening snap. There was no hepatosplenomegaly and no peripheral signs of endocarditis. Eight blood cultures were started, two of which grew S. epidermidis bacteria that were sensitive to methicillin and cloxacillin. Echocardiography was performed and showed mitral stenosis with a valve area of 1 cm2. The mitral valve was calcified without any vegetations seen. Cloxacillin, 2 g six times a day, was administered for 4 weeks. The temperature normalized, and the patient is well 4 months later. COMMENTS S. epidermidis is the most frequent cause of positive blood cultures in a hospital environment, be-

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cause it is the most common bacterial contaminant of blood cultures [4,5]. Nevertheless, only 6.3% of those having a blood culture positive for S. epidermidis have true S. epidermidis bacteremia [6]. Therefore, physicians have to decide whether isolation of this organism implies contamination or a real infection. True S. epidermidis bacteremia can be differentiated from S. epidermidis contamination by its detection on two or more isolated consecutive cultures [7]. Possible S. epidermidis endocarditis will be diagnosed if true S. epidermidis bacteremia is encountered in the presence of congenital or acquired heart disease [7-g]. In all of our patients, multiple blood cultures positive for S. epidermidis established the presence of true S. epidermidis bacteremia. Five of the seven patients have probable cases and the remaining two have possible cases of S. epidermidis endocarditis. Three of our patients were afebrile during the whole course of their disease. General symptoms such as weakness, anorexia, and weight loss were the main presenting symptoms, raising the suspicion of malignant disorders. The presence of embolic phenomenon was rare, and only one patient underwent aortic valve replacement. None of our patients was a drug addict. The port of entry was evident in only three of our patients (erysipelas, chronic osteomyelitis, and recent prostatectomy). In order to elucidate the characteristic clinical features of native valve S. epidermidis endocarditis, we summarized, in Table I, the clinical characteristics of all the patients described in the previous series [ 10-223. A review of the 85 patients described in a series on the subject showed that S. epidermidis tends to occur more frequently in male patients, with an age range of 22 to 82 years, which is similar to that of the general population affected by endocarditis [2326]. Only 25% of patients with S. epidermidis endocarditis exhibit embolic complications and 37% exhibit skin manifestations. The frequency of reported congestive heart failure is 31% in this group, with 27% of the patients needing valve replacement. New or progressive congestive heart failure, chronic congestive heart failure with severe aortic and mitral valve regurgitation, and new onset heart block prompted surgery in the majority of the patients who underwent a surgical procedure. The data concerning the pre-existing valvular lesions are insufficient to reach any conclusions concerning the affinity of S. epidermidis for a specific valvular lesion. Any attempt to compare specific characteristics of our patients and patients in previous series with S. epidermidis endocarditis with those of patients

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with endocarditis caused by other organisms is difficult. Different patient populations influence the clinical characteristics. Nevertheless, in comparison to general large series of endocarditis, the course of S. epidermidis endocarditis is subacute in nature with lower incidences of congestive heart failure and embolic phenomenon [23-261. In this respect, S. epidermidis is similar to infective endocarditis in the elderly [24,27-301. A delay in initiating appropriate therapy is more common in this age group. Therefore, it is important to remember that the presentation can be atypical, and a high index of suspicion is mandatory. Multiple blood cultures should be started, especially in the elderly, even in cases with only minimal clinical signs suggesting endocarditis.

ACKNOWLEDGMENT We wish to express our thanks to Raphael Rosenbaum for editorial assistance and to Mrs. Pnina Falk for secretarial assistance in preparing this manuscript.

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/ ARBER ET AL 24.Terpenning MS, Buggy BP, Kauffman CA. Infective endocarditis: clinical features in young and elderly patients. Am J Med 1987; 83: 626-34. 25. Cherubin HC. Infective endocarditis at the Presbyterian Hospital in New York City from 1938 to 1967. Am J Med 1971; 51: 83-91. 26. Von Reyn CF, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981; 94: 505-18. 27. CummingsV, FurmansS, Dunst M, Rubin IL. Subacute bacterial endocarditis in the older age group. JAMA 1960; 172: 137-41. 28. Watanakunakorn C, Tan JS, Phair JP. Some salient features of Staphylococcus aweus endocarditis. Am J Med 1973; 54: 473-81. 29. Applefeld MM, Hornick RB. Infective endocarditis in patients over age 60. Am Heart J 1974; 88: 90-4. 30. Roblins N, DeMaria A, Miller MH. Infective endocarditis in the elderly. South Med J 1980; 73: 1335-8.

Stapby/ococcus a/bus. Lancet 1951; 260: 146-8. 18. Ravitsky MA, Warres R, Gielchinsky I, Bernstein A, Rothfeld D. Staphylococcus epidefmidis endocarditis: case reports and review of the literature. J Med Sot New Jersey 1978; 75: 539-41. 19. Banks T, Fletcher R, Ali W. Infective endocarditis in heroin addicts. Am J Med 1973; 55: 444-51. 20. Conrad SA, West BC. Endocarditis caused by Staphylococcus xy/osus associated with intravenous drug abuse. J Infect Dis 1984; 1495: 826-7. 21. Wilhelm F, Hirsh HL, Hussey HH, Dowling HF. The treatment of acute bacterial endocarditis with penicillin. Ann Intern Med 1947; 26: 221-30. 22. Eisert J. Skin manifestations of subacute bacterial endocarditis. Cutis 1980; 25: 304-400. 23. Pelletier RG, Petersdorf LL. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals 1963-1972. Medicine (Baltimore) 1977; 56: 287-313.

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