Native-Valve Endocarditis Caused by Staphylococcus ...

Native-Valve Endocarditis Caused by Staphylococcus epidermidis A Histologically Confirmed Case BENJAMIN LITTENBERG, M.D., BRIAN COOPER, M.D., AND ROBERT LEVITZ, M.D.

STAPHYLOCOCCUS EPIDERMIDIS is the most common organism isolated from blood cultures at this institution. Conversely, it is rarely a well-documented cause of natural-valve bacterial endocarditis. However, several authors have reported series of patients with the clinical picture of endocarditis and S. epidermidis bacteremia.6'8'1 M2 Most of these cases have not been confirmed by examination of the valve, even when the patient underwent valve replacement or necropsy. We recently treated a patient with bacterial endocarditis of his native valve caused by S. epidermidis and confirmed by pathologic examination of the valve after surgery. Report of a Case A 63-year-old retired fireman was admitted to the hospital for confusion, abdominal pain, and an 18-kg weight loss over eight months. He had a history of 60 pack-years of tobacco abuse and heavy alcohol use. He had stopped drinking eight months before admission for unclear reasons. There was no history of heart disease, thoracic surgery, or rheumatic fever. On examination he was cachectic with a productive cough. His blood pressure was 90/65. His temperature was 37 °C. The fundi were normal. Heart examination revealed a 3/6 holosystolic murmur radiating to the left axilla. His chest had an increased anteroposterior diameter with ronchi, rales, and wheezes on auscultation. The extremities were without lesion.

Department of Medicine, Hartford Hospital, Hartford, and Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut

The white blood cell count was 13,000/ML (13 X 109/L), with 73% (0.73) polys, 10% (0.10) bands, 11% (0.11) lymphocytes, and 6% (0.06) monocytes. The hematocrit was 29% (0.29) and the erythrocyte sedimentation rate was 80 mm/hour. Urinalysis results were normal. Chest x-ray showed diffuse interstitial disease and a slightly increased heart size. The cardiogram showed normal sinus rhythym with normal axis and intervals and nonspecific ST- and T-wave changes. An echocardiogram revealed a grossly thickened mitral valve with a flail leaflet. A Doppler echocardiogram documented "wide-open mitral regurgitation." On the second hospital day, he had a cardiac arrest with ventricular fibrillation. He was electrically defibriUated and transferred to the cardiac intensive care unit. In the intensive care unit he was afebrile, combative, confused, and hypotensive. A pulmonary artery catheter revealed a pulmonary capillary wedge pressure of 17 mmHg on insertion. Over the next few days, he had brief episodes of heart failure with wedge pressures to 35 mmHg. Cardiac enzymes were elevated in the pattern of a subendocardial myocardial infarction. The creatine kinase peaked at 253 U/L. Blood cultures taken before his arrest grew S. epidermidis. Subsequent cultures confirmed this. Altogether, nine often blood cultures were positive for S. epidermidis. On thefifthhospital day, worsening abdominal pain,rightflankpain, and atrialfibrillationdeveloped. Urinalysis showed red blood cells and white blood cells in clumps with white blood cell casts. A renal scan was consistant with a right renal infarct. His maximum temperature to this time was 37.8 °C. He was taken to the operating room for porcine replacement of his mitral valve. The native valve was described as "little bits of yellow spaghetti." Tissue Gram's stain of the valve revealed gram-positive cocci (Fig. 1). Postoperatively, he did well on treatment with intravenous cefazolin. His abdominal pain and hematuria resolved, and his mental status improved markedly. At follow-up seven months later, he was home and feeling well.

Discussion Received March 31, 1986; received revised manuscript and accepted for publication June 10, 1986. Address reprint requests to Dr. Cooper: Department of Medicine, Hartford Hospital, Hartford, Connecticut 06115.

Coagulase-negative Staphylococci have emerged in the last two decades as major pathogens in device-related infections. These ubiquitous skin colonizers are frequently

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Staphylococcus epidermidis is among the most common organisms isolated from blood cultures. Conversely, it is rarely a welldocumented cause of natural-valve endocarditis. However, several authors have reported series of patients with the clinical picture of endocarditis and S. epidermidis bacteremia. Most of these cases have not been confirmed by examination of the valve. The authors present a case of natural-valve endocarditis caused by S. epidermidis with pathologic documentation of the offending agent. (Key words: Staphylococcal infections; Staphylococcus epidermidis; Bacterial endocarditis) Am J Clin Pathol 1987; 87: 408-410

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FlG. 1. Touch preparation of excised valve tissue demonstrating 5. epidermidis. Gram's stain (X100).

cubation (48 hours), and salt-supplemented media (5% NaCl). In addition, several colonies should be subcultured onto media containing 50-100 mg/L of methicillin and media containing similar concentrations of cephalosporins.12 The prevalence of MRSE varies. It is high in nosocomial infections, but most community-acquired isolates are susceptible to semisynthetic penicillins. Vancomycin is the drug of choice for MRSE. Fortunately, the isolate in our case was sensitive to methicillin and cephalosporins and was eradicated with cefazolin. S. epidermidis is a rare cause of natural-valve endocarditis and a common cause of contamination in blood cultures. When no other cause of endocarditis can be isolated in a patient with 51. epidermidis bacteremia, it should seriously be considered as the etiologic agent. References 1. Archer GL, Tenenbaum MJ: Antibiotic resistant Staphylococcus epidermidis in patients undergoing cardiac surgery. Antimicrob Agents Chemother 1980; 17:269-272 2. Arthur JD, Bass JW, Keiser JF, Harden LB, Brown SL: Nafcillin tolerant Staphylococcus epidermidis endocarditis. JAMA 1982; 247:487-488 3. Christensen GD, Parisi JT, Bisno AL, Simpson WA, Beachey EH: Characterization of clinically significant strains of coagulase-negative Staphylococci. J Clin Microbiol 1983; 18:258-269 4. Courtiss EH, Goldwyn RM, Anastasi GW: The fate of breast implants


seen in prosthetic valve endocarditis, orthopedic implant sepsis,10 augmentation mammoplasty,4 and catheterassociated bacteremia.13 This proclivity for foreign material may result from virulence factors such as slime. Slime is an extracellular mucopolysaccaride or glycocalyx that facilitates adherence of the organism to various surfaces, particularly plastic and other foreign bodies.3 5. epidermidis is also the most frequent contaminant in blood cultures. When isolated from the blood of a patient without an indwelling catheter or prosthetic device, it is difficult to separate contamination from clinically important infection. The reported incidence of native valve endocarditis with 5. epidermidis is 1-3% of all cases in most series,5 but often there is little documentation other than 5. epidermidis in culture from a patient with clinical endocarditis. There are few studies that demonstrate the organism within excised valve tissue. Conversely, the possibility of endocarditis is often glibly excluded in the patient with unexplained fever, S. epidermidis in the blood, and natural valves. The current case is of interest because gram-positive cocci were seen on the excised valve, confirming S. epidermidis as the pathogenic agent. Early reports indicated that most cases of 5. epidermidis endocarditis were sensitive to penicillin. Later, changing sensitivity patterns led to the use of semisynthetic penicillins and cephalosporins. As in prosthetic valve endocarditis, methicillin- and cephalosporin-resistant strains are now common.2,14 This issue has been clouded further by the recent awareness that routine susceptibility testing of S. epidermidis may falsely label some strains of this organism as susceptible to commonly used antimicrobials. This heterotypic or subpopulation resistance may be responsible for some failures of prophylaxis and treatment of S. epidermidis infections. Methicillin-resistant strains, in particular, may appear susceptible when tested by conventional means. Isolates should be screened for heterotypic resistance or resistance occurring in low-frequency subpopulations (10-4 to 10~6). There is often cross-resistance of methicillin-resistant S. epidermidis (MRSE) with other beta-lactam antibiotics. Cephalosporins that appear to have adequate activity by standard microtiter or disk diffussion technics have been shown to be cross-resistant with methicillin.9 Testing by disk or agar dilution methods will demonstrate methicillin resistance in 10-30% of isolates.14 Screening for subpopulations of resistant strains, one study found 17 of 27 isolates were methicillin resistant.1 A second study showed an 80% incidence of resistance.7 In order to maintain a high yield of methicillin-resistant subpopulations, the isolate must be tested with a high inoculum (1010 colony-forming units/L), prolonged in-

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with infections around them. Plast Reconstr Surg 1979; 63:812816 Finland M, Barnes MW: Changing etiology of bacterial endocarditis in the antibacterial era. Ann Intern Med 1970; 72:341-348 Geraci JE, Hanson KC, Giuliani ER: Endocarditis caused by ccagulase-negative Staphylococci. Mayo Clin Proc 1968; 43:420434 Karchmer AW, Archer GL, Dismukes WE: Staphylococcus epidermidis causing prosthetic valve endocarditis: Microbiologic and clinical observations as guides to therapy. Ann Intern Med 1983; 98:447-455 Keys TF, Hewitt WL; Endocarditis due to micrococci and Staphylococcus epidermidis. Arch Intern Med 1973; 132:216-220 Laverdiere M, Petersen P, Verhoef J, Williams DN, Sabath LD: In vitro activity of cephalosporins against methicillin-resistant coagulase-negative Staphylococci. J Infect Dis 1978; 137:245-250

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10. Patterson FP, Brown CS: The McKee-Farrar total hip replacement. J Bone Joint Surg 1972; 54:257-275 11. Quinn EL, Cox F. Staphylococcus albus (epidermidis) endocarditis: Report of 16 cases seen between 1953 and 1962. Antimicrob Agents Chemother 1963; 3:635-642 12. Ravitsky MA, Werres R, Gielchinsky I, Bernstein A, Rothfield D: Staphylococcus epidermidis endocarditis: Case reports and review of the literature. J Med Soc NJ 1978; 75:539-541 13. Sitges-Serra A, Puig P, Juarrieta E, Garau J, Alastrue A, Sitges-Creus A: Catheter sepsis due to Staphylococcus epidermidis during parenteral nutrition. Surg Gynecol Obstet 1980; 151:481-483 14. Tuazon CU, Miller H: Clinical and microbiologic aspects of serious infections caused by Staphylococcus epidermidis. Scand J Infect Dis 1983; 15:347-360 15. Watanakunakorn C: Prosthetic valve endocarditis. Prog Cardiovasc Dis 1979; 22:181-192

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