A 66-Year-Old Man With Severe Fatigue

Correct Answer: D. Two more separate sets of blood cultures drawn 30 minutes apart should be obtained prior to initiation of antibiotics.

Discussion. Although the diagnosis of bacterial endocarditis of native values is far less common in recent decades due to the marked decrease of rheumatic valvular heart disease, we all need to have our antennae up for any patient with an unexplained fever and a heart murmur, as was the case in the presented patient. Our patient also had a predisposing cardiac condition (the bicuspid aortic valve), diabetes, and dentition issues, which were likely the source of the bacterial seeding.¹ The conjunctival hemorrhage, a microembolic/immunologic finding, helped confirm the diagnosis. Indeed, taken with the confirmed physical findings of fever and a heart murmur, present in 90% and 75% of endocarditis cases, respectively,^{1, 2} the diagnosis was strongly suggested and appropriate testing for confirmation was ordered.

This brings us to the Modified Duke Criteria (MDC), which is often used for the diagnosis of bacterial endocarditis. For the MDC, the evaluation for major clinical criteria includes: (1) Positive blood culture, defined as two separate positive cultures demonstrating “typical organisms”, (gram (+) cocci); (2) positive echocardiography demonstrating vegetation, abscess, or valve dehiscence in a prosthetic case; and (3) new valvular regurgitation.

Alternatively, minor clinical criteria include: the presence of predisposing cardiac pathology or intravenous drug use; temperature >100.4˚^F; vascular phenomena (eg, emboli, conjunctival hemorrhage or Janeway lesions); immune phenomena (eg, glomerulonephritis, Roth spots); and atypical patterns of positive blood cultures.

A definitive diagnosis is defined as the presence of two major criteria, all five minor criteria, or one major and three minor criteria. Possible endocarditis includes the presence of one major and three minor criteria. Any accounting less than the above is not diagnostic.²

Our patient was awaiting echocardiography and the results of a blood culture, but he was already well on his way to the definitive diagnosis of bacterial endocarditis at the time of evaluation. The Modified Duke Criteria has an 80% sensitivity and 90% specificity for bacterial endocarditis.²

We need to remember that at least two blood cultures must be drawn separately for diagnosis, which is the minimal microbiologic criterion. Three sets is a commonly used scheme, making Answer D the correct answer. Answer A addresses the issue of using newer molecular and serologic methods, such as polymerase chain reaction amplification for bacterial pathogens. Current techniques seem to require vegetation material, so this is not yet part of the typical microbiological confirmation. Therefore, Answer A is not optimal here. We continue to use blood cultures to satisfy the first major criterion in diagnosing bacterial endocarditis.¹

The second major criterion is echocardiography. As much as we love to hone our physical diagnosis skills with auscultating new and/or changing murmurs, hearing them is not enough because one cannot hear a vegetation. However, an echocardiogram can demonstrate one and the criterion is demonstration of such a vegetation. We now know that valvular disease and injury result in a fibrin/platelet mix of material onto which circulating bacteria can adhere and multiply and where neutrophils/antibodies cannot effectively get at them. The toxic amalgam and the number of organisms grows in size, creating a macroscopic “vegetation” demonstrable by today’s imaging techniques. Transthoracic echocardiography (TTE) is 50% to 60% sensitive and 95% specific. Transesophagael (TEE) is even better, at 90% (+) sensitive and again 95% specific. Both also add an evaluation of cardiac status via ejection fraction, but TEE yields additional information such as spread with cardiac valvular abscess and extension, which are indicators for early surgery.^2-4 Answer B brings next generation imaging techniques into play, specifically PET-CT scanning. To date, this method is used to evaluate prosthetic valve endocarditis.³ But for now, it is not part of usual endocarditis evaluation in native valve disease, making Answer B an incorrect one at this time.

Briefly, native valve endocarditis management may involve antibiotics, but in a minority of cases, antibiotics are incapable of a cure. Worse yet, a cardiac or systemic complication may occur. In such cases, surgery is required. The three major indications for surgery are: (1) Chronic heart failure generally resulting from destruction of mitral or aortic valves with leak and severe acute regurgitation pathophysiology or fistula; (2) uncontrolled infection despite antibiotics; and (3) the prevention of systemic embolization, the marker for which seems to be a vegetation of ≥ 1 cm.⁵

Regarding our patient, there was not nearly enough data present to justify surgery, making Answer C incorrect.

Outcome and follow-up. On the morning of day 2, the microbiology lab reported that his initial blood culture test showed viridans streptococci. Two subsequent blood cultures were drawn, roughly 12 hours apart. A TTE demonstrated normal ejection fraction and mild AS (valvular gradient 25 mmHg) with a clearly demonstrable vegetation of ~ 0.4 cm on one of the bicuspids AV leaflets. No regurgitant flow was seen. Penicillin (18 million units/d) was initiated intravenously.

The next day, the two subsequent blood cultures were reported with the same organism. Excellent sensitivity to penicillin was demonstrated. The patient’s temperature normalized on days 4 and 5. The plan was to continue the intravenous penicillin using home care for 4-weeks duration.

What’s the Take Home? Bacterial endocarditis of native valves is far less common than in prior decades due to the significant eradication of rheumatic valvular heart disease. Today’s cases have the epidemiology of predisposing conditions that include degenerative valve diseases and abnormalities, such as aortic stenosis or mitral valve prolapse. Clinical presentation continues to be fevers and a heart murmur.  Even with this presentation, clinicians suspecting endocarditis should look for findings such as conjunctival hemorrhage, splinter nail hemorrhages, and immunologic phenomena. Definitive diagnosis involves the Modified Duke Criteria, the mainstays of which are positive blood cultures for “typical” bacteria (usually a gram (+) coccus) in appropriately obtained blood cultures and the demonstration of the hallmark pathologic and radiologic lesion – a vegetation – by appropriate imaging techniques of TTE and TEE. Most cases will respond to antibiotics, the choice and duration of which depend on sensitivity analysis. In a minority of patients, endocarditis can cause systemic (embolization) and cardiac complications (valve leaks with acute regurgitation and acute chronic heart failure). These complications likely would require surgical intervention. Fortunately, our patient did not require surgery.

AFFILIATIONS:
¹Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania
²Department of Medicine, Temple University Hospital, Philadelphia, Pennsylvania

CITATION:
Rubin RN. A 66-year-old man with severe fatigue. Consultant. 2023;63(2):e12. doi:10.25270/con.2023.02.000003

DISCLOSURES:
The author reports no relevant financial relationships.

CORRESPONDENCE:
Ronald N. Rubin, MD, Temple University Hospital, 3401 N Broad Street, Philadelphia, PA 19140 (blooddocrnr@yahoo.com)