Fever, Myalgias, and Fatigue in a Woman Receiving Dialysis

For several days, a 60-year-old woman has had fever, myalgias, fatigue, poor appetite, and diminished oral intake. She denies cough, sputum production, and urinary symptoms.

HISTORY
The patient has a long history of hypertension, which resulted in end-stage renal failure that has required hemodialysis for the past year. Her long-term medications include lisinopril, metoprolol, and amlodipine. She has no history of paroxysmal nocturnal dyspnea, exertional dyspnea, or pedal edema. An echocardiogram obtained 1 year ago showed left ventricular hypertrophy and an ejection fraction of 65%. She denies alcohol or illicit drug use.

PHYSICAL EXAMINATION
Temperature is 38.6^oC (101.7^oF); heart rate, 108 beats per minute; and blood pressure, 108/84 mm Hg. Head, ears, eyes, nose, and throat are normal, and lungs are clear. A grade 2/6 systolic murmur is evident but is difficult to characterize because of tachycardia. The right subclavian hemodialysis access site appears slightly red. Results of abdominal, neurologic, and extremity examinations are normal.

LABORATORY AND IMAGING RESULTS
Creatinine level is 10 mg/dL; blood urea nitrogen, 41 mg/dL; potassium, 5.1 mEq/L; and sodium, 134 mEq/L. Anion gap is not elevated. Hemoglobin level is 8.7 g/dL, and white blood cell count is 11,900/μL. Chest film shows no infiltrates.

INITIAL HOSPITAL COURSE
Because of concern that the hemodialysis access site is infected, the patient is hospitalized. Blood samples for culture are obtained, and vancomycin is started at a renally adjusted dosage. The patient’s temperature decreases to 37.2^oC (99^oF), and she seems to improve. However, on her third day in the hospital, blood cultures from the first and second days show chains of gram-positive cocci. Vancomycin is continued, the hemodialysis line is removed, and an echocardiogram is ordered. That night the patient reports chest tightness and significant orthopnea. Her temperature remains 37.2^oC (99^oF), but blood pressure has fallen to 90/70 mm Hg. A third culture of previously drawn blood is positive for Enterococcus faecalis. An urgent echocardiogram reveals a left ventricular ejection fraction of 50% and vegetations on the aortic and mitral valves. The vegetations on the anterior leaflet of the mitral valve have resulted in severe mitral regurgitation directed posteriorly. Moderate aortic regurgitation is also evident. Gentamicin is added to the patient’s antibiotic regimen.

What is the most appropriate next step for this patient?
A. Repeat blood cultures and test for antibiotic resistance.
B. Add amphotericin to the antibiotic regimen.
C. Initiate medical therapy for congestive heart failure (CHF) and check for diuresis.
D. Obtain a cardiothoracic surgery evaluation for urgent valve replacement or repair.

(Answer and discussion on next page.)

CORRECT ANSWER: D

This patient has bacterial endocarditis. The findings here fulfill the modified Duke criteria for the disease.¹ The Duke guidelines establish 2 types of major criteria:

•Microbiologic-which include the presence on 2 separate blood cultures of typical organisms, such as enterococci without a primary focus; typical organisms isolated from persistently positive blood cultures; or a single blood culture that shows Coxiella burnetii.

•Endocardial involvement-which include new valvular regurgitation or vegetations detected by echocardiography.

The presence of criteria from the 2 major types, as seen in this patient, is diagnostic. One major criterion plus at least 3 minor criteria is also diagnostic of endocarditis. The minor criteria include:

•Epidemiologic factors that predispose to endocarditis- for example, preexisting valvular disease or injection drug use.

•Vascular phenomena, such as Janeway hemorrhagic lesions.

•Immunologic phenomena, such as Osler nodes or glomerulonephritis.

The source of this patient’s endocarditis was the infected vascular access catheter; this resulted in bacteremia and subsequent valvular infection. Blood cultures repeatedly showed typical microorganisms (enterococci), and an echocardiogram revealed vegetations on her aortic and mitral valves. Thus, the diagnosis is not in question.

The enterococcal infection was appropriately treated with an aggressive, synergistic bactericidal combination of a cell wall–active antibiotic (vancomycin) and an aminoglycoside (gentamicin). The patient’s fever abated in an appropriate period. (In 90% of patients with endocarditis, fever resolves within 14 days, regardless of the causative organism. A persistent fever suggests spread of the infection or drug resistance.²) Repeating blood cultures and testing for resistance (choice A) seems reasonable, particularly since resistance can be a problem with enterococci. However, the original culture samples should suffice for antibiotic testing. More important, this patient has hemodynamic complications, which cannot be treated by antibiotic manipulation alone. For this reason, both choice A and choice B (empirically adding an antifungal to the regimen) are incorrect.

Indications for surgery. This life-threatening infection has made the patient severely ill, and obvious CHF has developed. However, to invest time in the implementation of a standard medical CHF regimen (choice C) is a suboptimal strategy here. Medical therapy and surgery are both required to reduce mortality in patients with endocarditis who have CHF, perivalvular abscess, or uncontrolled infection despite antibiotics.³ Surgery may also be indicated for patients with endocarditis caused by certain organisms (eg, pseudomonads, fungi) that respond poorly to antibiotics alone. CHF is perhaps the strongest indication for surgery. Mortality among patients with endocarditis and moderate to severe CHF who receive medical therapy alone is 56% to 86%, compared with a mortality of 11% to 35% among those who are treated with both medical and surgical therapy.³ Moreover, delaying surgery in this setting increases mortality; the optimal time is before severe hemodynamic derangement develops. The new and florid symptoms of CHF in this patient and the strikingly changed and abnormal echocardiogram suggest a rapid and ominous hemodynamic decline that favors prompt surgical valve replacement.

Outcome of this case. The patient was given pressor agents but continued to worsen both symptomatically and hemodynamically. She was taken to surgery. Vegetations were found on the aortic, mitral, and tricuspid valves; perivalvular involvement was also evident. All 3 infected valves were replaced; however, the patient remained hypotensive and continued to require pressor therapy. She died 2 days after surgery.

References:

REFERENCES:

1.

Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteriafor the diagnosis of infective endocarditis.

Clin Infect Dis.

2000;30:633-638.

2.

Mylonakis E, Calderwood SB. Infective endocarditis in adults.

N Engl J Med.

2001;345:1318-1330.

3.

Alexiou C, Langley SM, Stafford H, et al. Surgery for active culture-positiveendocarditis: determinants of early and late outcome.

Ann Thorac Surg.

2000;69:1448-1454.