An Older Female with Fevers, Myalgias, and Fatigue – Part II

Ronald Rubin, MD—Series Editor

This case was first introduced in the June 2014 column. In this second part, we discuss her management.

A 67-year-old female was admitted for a several day history of fevers, myalgias, and fatigue. She also noted poor appetite and diminished oral intake during this time. She denied cough or production of sputum as well as dysuria or other urinary symptoms.


Significant past medical history reveals long-term hypertension with subsequent end-stage renal failure on hemodialysis for the past year. Her medicines include lisinopril, metroprolol, and amlodipine, in addition to a standard renal failure/hemodialysis regimen, including erythropoietin to maintain hemoglobin levels between 10 g/dL to 11 g/dL. 

She denies alcohol use or drug abuse of any kind. Systems review was negative for paroxysmal nocturnal dyspnea, exertional dyspnea, or pedal edema.

Physical Examination

Upon admission, physical exam revealed temperature
of 101° F, pulse of 108 beats per minute, and blood pressure 108/84 mm Hg. Head, eyes, ears, nose, and throat exams
was nonremarkable. 

Chest showed clear lungs. There was some redness at the right subclavian hemodialysis access site. The cardiac exam revealed a tachycardia with a grade II/VI systolic murmur at the apex, otherwise more difficult to characterize due to the tachycardia. Abdominal, extremity, and neurologic exam were negative. 

Laboratory Tests

Laboratory exam showed creatinine levels of 10 mg/dL, blood urine nitrogen levels of 41 levels of mg/dL, potassium levels of 5.1 mEq/L, sodium levels of 134 meq/L, and no anion gap. Hemoglobin was 8.7 g/dL and white blood cell count was 11.9 K/mm3. Chest x-ray had no infiltrates.

Initial Treatment

The patient was admitted with concern regarding an infected access site. Blood cultures were obtained and renally-adjusted dose vancomycin was started. Her temperature initially declined to 99°F and she subjectively improved. However, on the third hospital day, positive blood cultures from both the first 2 days of admission were reported as gram positive cocci in chains. 

Vancomycin was continued and the line removed. An echocardiogram was ordered. That night she reported chest tightness and significant shortness of breath with difficulty lying down. Temperature was 99°F but blood pressure was 90/70 mm Hg. 

Yet another previously drawn blood culture was positive and all were now being identified as Enterococcus faecalis. An urgent echocardiogram revealed left ventricular ejection fraction of 50%, with vegetations on the aortic and mitral valves. The large vegetation of the anterior leaflet of the mitral valve resulted in severe mitral regurgitation directed posteriorly. There was also moderate aortic regurgitation. Gentamycin was added to her antibiotic regimen.

Which of the following is a correct statement about her management?

A. She should be anticoagulated on a regimen including both anticoagulants and antiplatelet agents.

B. She should be hemodynamically stabilized over the next several days with an effective congestive heart failure regimen.

C. She should receive additional antibiotics to better control her infection.

D. She requires emergent surgery as she manifests multiple indications for emergent/urgent surgery.

(Answer and discussion on next page)

Correct Answer: D, she requires emergent surgery as she manifests multiple indications for emergent/urgent surgery.

This patient is suffering from bacterial endocarditis. In fact, the findings presented in the case fulfill the modified Duke criteria for diagnosing endocarditis.1 These guidelines continue to be used in practice and establish 2 types of major criteria: 

• Microbiological involvement includes typical organisms, such as E. faecalis, from 2 separate blood cultures without a primary focus or typical microorganisms isolated from 2 persistently positive blood cultures (our patient’s situation) or single blood cultures of Coxiella burnetti

• Endocardial involvement criteria include new valvular regurgitation or a positive echocardiogram for vegetations. The presence of the 2 major criteria as seen here is diagnostic. 

Minor criteria include epidemiologic predisposition to endocarditis—including preexisting valvular disease and injection drug use, vascular phenomena (eg, Janeway’s hemorrhagic lesions), and immunologic phenomena (eg, Osler nodes and glomeronephritis). 

Note: One major criterion plus at least 3 minor criteria also define endocarditis. Our patient’s source of infection was the infected vascular access catheter, which resulted in bacteremia that subsequently infected her valves. A “typical microorganism,” E. faecalis, was repeatedly cultured from her blood and echocardiogram demonstrated vegetations of her aortic and mitral valves.


Thus, the diagnosis is not in question. The enterococcus was appropriately treated with an aggressive, synergistic bactericidal combination of a cell wall active antibiotic (vancomycin) plus an aminoglycoside (gentamycin) and she defervesced in the proper time frame. Fever should resolve in 90% of cases regardless of organism within 14 days. When fever is persistent, extension of infection or drug resistance should be considered.2 

Adding more antibiotics (Answer C) is an interesting choice here, particularly since enterococci is the involved organism and resistance can be a problem with this microbe. However, she eventually was receiving a regimen of gentamycin and a cell wall active antibiotic (vancomycin) which has been shown effective in most situations of enterococcus endocarditis.2 More importantly the complication being described is hemodynamic and cannot be addressed by antibiotic manipulation alone.

Our patient is indeed ill with a life-threatening infection and has developed obvious acute and severe congestive heart failure (CHF). There are indications where combined medical and surgical therapy decreases endocarditits mortality, which includes CHF, perivalvular abscess, and uncontrolled infection despite antibiotics.3 Large vegetations may also be a factor.4 Also, certain organisms (eg, pseudomonas, fungi) have been shown to have poor outcomes using only antibiotic regimens, requiring surgery. 

CHF is perhaps the strongest surgical indication. Medically treated patients with moderate to severe CHF have a 56% to 86% mortality versus an 11% to 35% mortality in cases treated with combined medical and surgical therapy.

As many as 50% of endocarditis cases now receive early valve replacement surgery.2 Delay in surgery in this setting increases mortality and the optimal timing is prior to severe hemodynamic derangement. The new and florid symptoms of CHF and the strikingly changed and abnormal echocardiogram in our case suggest a brisk and ominous decrement in hemodynamics, which favors a prompt surgical attempt at valve replacement. To invest time in a CHF regimen (Answer B) is suboptimal in this case and findings presented here.

Answer A is an interesting slant on the cerebral presentation and complications of endocarditis. This situation has become more prevalent in recent decades such that cerebral complications are now the most common and most severe extracardiac complications of endocarditis.2,4 Embolic ischemic and hemorrhagic strokes are most frequent. A recent trial has suggested that finding a large (>1 cm to 1.5 cm) vegetation significantly jeopardizes a patient for embolic risk and/or hospital death that such a finding is its own indication for surgery apart from other hemodynamic indications.4 Pharmacologic attempts at embolism prevention have been subject to trials and at best add nothing and possibly increase cerebral hemorrhage and mortality.2 Thus Answer A is incorrect.

Outcome of the Case

The patient was placed on pressor agents but continued to worsen symptomatically and hemodynamically. That evening she was taken to the operating room where vegetations and involvement were found on the aortic and mitral valves, which were then replaced. She initially remained hypotensive and required pressors but slowly improved over a 10-day period. She remained afebrile and all surveillance blood cultures remained negative. A 6-week antibiotic course was planned.

Take-Home Message

Surgical indications in endocarditis include uncontrolled infection despite antibiotics, spread of infection to valve ring and septum, and most commonly and importantly, development of CHF due to valve dysfunction. A new candidate for early surgery is large vegetations, which can present an embolism risk, especially to the brain. The patient’s best chance is appropriate prompt evaluation and surgery in these situations.

Ronald Rubin, MD, is a professor of medicine at Temple University School of Medicine and chief of clinical hematology in the department of medicine at Temple University Hospital, both in Philadelphia.


1. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30(4):633-638.

2.Hoen B, Duval X. Infective endocarditis. N Engl J Med. 2013;368:1425-1434.

3.Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Eng J Med. 2012;366:2466-2473.

4.Alexiou C, Langly SM, Stafford H, et al. Surgery for active culture positive endocarditis: determination of early and late outcome. Ann Thorac Surg. 2000;69:1448-1454.