Man With Fever, Chills, and a History of Injection Drug Use

A 32-year-old man presents with a 4-day history of fever (temperature as high as 38.8°C to 39.4°C [102°F to 103°F])with severe rigors, chills, and profuse night sweats; generalized myalgias, including dull, aching headache; and dry cough.

History. The patient has been an injection drug user for the past 4 years. He is currently enrolled in a methadone program; his maintenance dosage is 65 mg/d. However, he has been injecting heroin again for the past 4 months. About 2 months ago, he was hospitalized for 10 days for methicillin-resistant Staphylococcus aureus (MRSA) infection and cellulitis of the left thumb, into which he had injected heroin. The cellulitis resolved completely after intravenous vancomycin therapy, and there is no evidence of osteomyelitis.

The patient has had no contact with sick persons. He has no chest pain and displays minimal exertional dyspnea with good effort tolerance. There is no history of hemoptysis, palpitations, ankle edema, weight loss, nausea, vomiting, diarrhea, abdominal pain, hematemesis,melena, visual symptoms, weakness, paresthesias, seizures, syncope, urinary symptoms, rashes, or adenopathy.

The patient's history includes hepatitis C, which was treated with peginterferon and ribavirin 5 years earlier. Results of HIV testing at that time were negative. Both the patient's parents have type 2 diabetes and hypertension.

The patient regularly drinks 2 or 3 beers (6 oz each) a day but does not smoke. He has a monogamous relationship with his wife. He has had no blood transfusions. He has no tattoos and no history of foreign travel.

Examination. The patient appears ill and poorly nourished. The heart rate is 120 beats per minute and regular; temperature, 39°C (102.2°F); respiration rate, 24 breaths per minute; blood pressure (right arm), 106/60 mm Hg. Skin and mucous membranes are dry. Examination of the head and neck shows no erythema, evidence of candidal infection, or icterus. Jugular vein pulse is normal; the apex beat is within normal limits. Heart sounds are normal.

Chest examination shows symmetric, equal movements bilaterally. The trachea is centrally located. Harsh bronchovascular breath sounds with prolonged expiration are noted, except at the left base, where air entry is poor. Scattered rales are audible bilaterally. Abdominal examination reveals no organomegaly, tenderness, or evidence of ascites. Results of the neurologic examination are normal. The neck is supple, and there are no meningeal or cerebellar signs.

Laboratory studies. White blood cell (WBC) count, 20,150/µL, with 84% polymorphonuclear leukocytes, 12% lymphocytes, and 4% monocytes; hemoglobin level, 12.9 g/dL; platelet count, 186,000/µL; erythrocyte sedimentation rate (ESR), 122 mm/h. Urinalysis reveals 1+ protein, 0 to 5 leukocytes, and no red blood cells. Blood glucose level is 102 mg/dL; blood urea nitrogen, 24 mg/dL; creatinine, 1 mg/dL; serum sodium, 131 mEq/L; potassium, 3.4 mEq/L; chloride, 95 mEq/L; and bicarbonate, 26 mEq/L. Total protein, 6.9 g; albumin, 3.8 g; total bilirubin, 1.4 mg/dL; conjugated bilirubin, 0.8 mg/dL; aspartate aminotransferase, 24 IU/L; alanine aminotransferase, 22 IU/L; and alkaline phosphatase, 112 IU/L. An ECG reveals sinus tachycardia.

A chest radiograph and CT scan are shown here.

Based on the clinical and radiographic findings, what further investigation is warranted?

A. Cardiac enzyme measurement

B. Open lung biopsy

C. Bronchoscopy

D. Transesophageal echocardiography (TEE)

E. Two-dimensional echocardiography

(Answer and discussion begin on the next page.)

EPIDEMIOLOGY

In the United States, the incidence of community-acquired native valve endocarditis has increased from 1.7 to 6.2 cases per 100,000 person-years. The male-to-female ratio is 1.7 to 1. Because of the increasing numbers of injection drug users, more cases of infective endocarditis have been seen in younger persons. The incidence among injection drug users is estimated at 150 to 200 cases per 100,000 person-years; it may be higher among patients with known valvular heart disease.

MICROBIOLOGY

Infective endocarditis denotes microbial infection of the cardiac valves and, less frequently, of the mural endocardium or septal defects. Any microorganism can cause endocarditis. Among injection drug users, right-sided endocarditis predominates; one of the following organisms is usually involved:

•Gram-positive: S aureus is the pathogen most commonly associated with endocarditis (17% to 40% of cases). It can be either sensitive or resistant to methicillin. Viridans streptococci may attack native heart valves in all patients with congenital or acquired valvular disease.

•Gram-negative: Pseudomonas aeruginosa and Serratia marcescens infections have been reported.

•Fungi: Consider Candida albicans and non-albicans fungi if initial bacterial cultures are negative and if the patient has not been taking antibiotics.

CLINICAL MANIFESTATIONS

Manifestations are extremely diverse and may mimic pulmonary, neurologic, renal, or joint disease. Peripheral manifestations, such as Osler nodes, Roth spots, Janeway lesions, and subungual (splinter) hemorrhages, occur less commonly.

The onset may be abrupt or insidious. The early manifestations may be vague flu-like symptoms. The patient may complain of malaise, fatigue, weakness, myalgia, arthralgia, night sweats, or weight loss. In 90% to 95% of cases, these signs are associated with high fever, chills, and rigors or--more ominously--symptoms of frank congestive heart failure (CHF) with progressive dyspnea; orthopnea; ankle edema; or embolic phenomena, such as septic emboli in the lungs, spleen, kidney, or brain.

Although heart murmurs are usually present in native valve endocarditis, they may be absent in injection drug users.

DIAGNOSIS

Because infective endocarditis can mimic any systemic disorder and heart murmur may be absent, a high index of suspicion is essential to establish the diagnosis promptly and to institute aggressive therapy in injection drug users.

The principal diagnostic criteria are:

•Positive blood cultures from 2 separate specimens.

•Evidence of endocardial involvement, with positive findings on TEE.

Ancillary test results that may be helpful include leukocytosis with left shift, elevated ESR, and microscopic hematuria and proteinuria on urinalysis. A baseline ECG may reveal chamber enlargement or conduction defects. A chest radiograph may show cardiomegaly, evidence of CHF, or septic emboli.

TREATMENT

Successful treatment depends on selection of the appropriate antimicrobial therapy after identification of the culprit organism with specific sensitivity. In injection drug users, empiric therapy with vancomycin and gentamicin is initiated before the offending pathogen is identified.

For methicillin-sensitive S aureus, the regimen of choice is nafcillin or oxacillin, 2 g q4h, in combination with gentamicin, 1 mg/kg IM or IV q8h, or rifampin, 300 mg PO or IV q12h for 2 weeks.

For MRSA, first-line treatment is vancomycin, 0.5 g q6h (with regular monitoring of peak and trough levels), in combination with gentamicin andrifampin, dosed as above. Therapy is continued for 4 to 6 weeks.

About 25% of patients with severe or complicated endocarditis undergo valve replacement surgery. The chief indications for surgery are:

•Poor response to antimicrobial therapy, with persistent fever and positive blood cultures.

•Refractory moderate or severe CHF.

•Perivalvular invasion or myocardial abscess, as evidenced by persistent fever or ECG changes that suggest new conduction defects.

•Systemic or arterial embolization.

•Fungal endocarditis.

•Large, bulky vegetation.

References:

FOR MORE INFORMATION:

• Amin NM. Infective endocarditis. In: Rakel RE, ed. Conn's Current Therapy. Philadelphia: WB Saunders Co; 2000:297-303.
• Chambers HF, Korzeniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine (Baltimore). 1983;62:170-177.
• Giessel BE, Koenig CJ, Blake RL Jr. Management of bacterial endocarditis. Am Fam Physician. 2000;61:1725-1732.
• Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:1318-1330.