Case 1: Endocarditis follow-up
A 45-year-old man being treated for infective endocarditis is seen for a follow-up examination. He was diagnosed with endocarditis 1 week ago after presenting with fatigue and fever. Initial transthoracic echocardiogram showed a bicuspid aortic valve with a small vegetation but was otherwise normal. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus, and intravenous nafcillin was initiated. Blood cultures obtained 48 hours and 72 hours after starting antibiotic therapy showed no growth.
On physical examination, temperature is 37.8 °C (100.0 °F), blood pressure is 128/78 mm Hg, pulse rate is 88/min, and respiration rate is 16/min. BMI is 25. Physical examination reveals no cutaneous or ocular stigmata of bacterial endocarditis. Cardiac examination reveals a grade 2/6 early systolic murmur at the base of the heart, unchanged from previous examinations. The remainder of the physical examination is normal.
Electrocardiogram is unchanged from the time of diagnosis except for an increase in the PR interval from 120 to 210 ms.
Which of the following is the most appropriate next step in management?
A. Cardiac CT
B. Continued antibiotic therapy without additional testing
C. Repeat transthoracic echocardiogram
D. Transesophageal echocardiogram
Case 2: Bicuspid aortic valve and fever
A 56-year-old man is evaluated in the hospital for a 2-week history of fevers and malaise. Medical history is significant for a bicuspid aortic valve. The patient takes no medications.
On physical examination, temperature is 38.5 °C (101.3 °F), blood pressure is 140/50 mm Hg, pulse rate is 98/min, and respiration rate is 16/min. There is no jugular venous distention. The lungs are clear. Cardiac examination reveals a grade 1/6 diastolic murmur. There are no signs of peripheral embolic disease. No lower extremity edema is present.
Electrocardiogram shows normal sinus rhythm, a PR interval of 230 ms, and nonspecific T-wave changes. Except for the increased PR interval, there are no changes compared with a prior tracing. A transthoracic echocardiogram shows a 6-mm vegetation on the aortic valve with mild to moderate aortic regurgitation. A transesophageal echocardiogram confirms the valve findings and suggests the presence of an area of fluid around the aortic annulus posterior to the vegetation, indicative of an aortic root abscess.
Blood cultures are positive for Staphylococcus aureus sensitive to methicillin. Appropriate antibiotics are started.
Which of the following is the most appropriate treatment?
A. Antibiotic therapy for 6 weeks and then reassess
B. Antibiotic therapy for 3 months and then reassess
C. Aortic valve replacement after 6 weeks of antibiotic therapy
D. Urgent aortic valve replacement
Case 3: Catheter infection
A 57-year-old woman is evaluated for blood cultures growing yeast during long-term intravenous antibiotic therapy. She has completed 4 weeks of a planned 6-week course of intravenous antibiotics for methicillin-sensitive Staphylococcus aureus infective endocarditis. A peripherally inserted central venous catheter (PICC) was placed at the beginning of her treatment. She developed a high fever 3 days ago, and blood cultures drawn peripherally and through the catheter at that time grew Candida species; further identification is pending. Medical history is otherwise negative, and her only medication is nafcillin.
On physical examination, temperature is 37.8 °C (100.0 °F), blood pressure is 126/80 mm Hg, pulse rate is 82/min, and respiration rate is 16/min. The eye grounds are clear. Chest examination is unremarkable. Cardiac auscultation reveals a grade 2/6 crescendo-decrescendo murmur at the right upper sternal border. She has no spinal tenderness. The right brachial PICC site is without erythema, drainage, or tenderness.
In addition to continuing intravenous antibiotic therapy, which of the following is the most appropriate management?
A. Continue PICC use
B. Continue PICC use and add antifungal therapy
C. Remove PICC
D. Remove PICC and add antifungal therapy
Case 4: Declining kidney function
A 24-year-old man is evaluated in the hospital for progressively worsening kidney function. He was admitted 5 days ago with fevers and was diagnosed with endocarditis with methicillin-resistant Staphylococcus aureus. Intravenous vancomycin was started and adjusted daily to target levels of 15 to 20 µg/mL (10.4-13.8 µmol/L). Since admission, his fevers have resolved, but his serum creatinine level has gradually increased. Medical history includes two previous admissions for staphylococcal endocarditis treated with prolonged courses of antibiotics. He has occasionally used injection drugs, including heroin, during the past 4 years. His only medication is vancomycin.
On physical examination, temperature is 37.3 °C (99.2 °F), blood pressure is 110/70 mm Hg, pulse rate is 92/min, and respiration rate is 18/min. BMI is 22. Cardiac examination is notable for a soft diastolic murmur along the left sternal border. There is trace lower extremity edema. There is no skin rash or arthritis.
Laboratory studies show low C3, normal C4, creatinine of 2.8 mg/dL (247.5 µmol/L) (1.5 mg/dL [132.6 µmol/L] on admission), and negative cryoglobulins. Urinalysis shows 3+ blood, 2+ protein, 30-40 erythrocytes/hpf, 10-15 leukocytes/hpf, and erythrocyte casts.
Transthoracic ultrasound shows moderate aortic regurgitation without vegetations (confirmed on transesophageal ultrasound). Kidney ultrasound shows normal-sized, mildly echogenic kidneys. Doppler study of the renal arteries and veins is normal.
Which of the following is the most appropriate management?
A. Initiate glucocorticoids
B. Schedule a kidney biopsy
C. Switch vancomycin to daptomycin
D. Continue current therapy
Case 5: Rash after endocarditis
A 44-year-old man was admitted to the hospital 2 weeks ago with fever and a new heart murmur and was diagnosed with native valve endocarditis. He was treated initially with broad-spectrum antibiotics with narrowing of his antimicrobial therapy to intravenous nafcillin based on culture and sensitivity results. He was discharged on the third hospital day to complete a 6-week course of intravenous antibiotic therapy. Although he had done well since discharge, he presents 11 days later with new fever and a rash.
On physical examination, temperature is 38.3 °C (100.9 °F), blood pressure is 115/78 mm Hg, pulse rate is 110/min, and respiration rate is 12/min. There is mild facial edema and lymphadenopathy of his cervical and axillary lymph nodes. The lungs are clear. Cardiac examination shows mild tachycardia and a grade 2/6 systolic murmur, unchanged from his last examination. Skin examination reveals diffuse erythema on his trunk, proximal extremities, and face. The remainder of his examination is unremarkable.
Laboratory studies show a leukocyte count of 12,100/µL (12.1 × 109/L) with 54% neutrophils, 31% lymphocytes, and 15% eosinophils; normal albumin; alanine aminotransferase of 147 U/L; aspartate aminotransferase of 156 U/L; and normal bilirubin. Repeat blood culture results are pending.
Which of the following is the most likely diagnosis?
A. Drug reaction with eosinophilia and systemic symptoms
B. Morbilliform drug exanthem
C. Stevens-Johnson syndrome
Answers and commentary
Correct answer: D. Transesophageal echocardiogram.
This patient should undergo transesophageal echocardiography (TEE). He has evidence of a new conduction defect on electrocardiogram suggesting a possible perivalvular abscess complicating Staphylococcus aureus infective endocarditis. Perivalvular abscesses may be present in 30% to 40% of patients with infective endocarditis, and the risk may be further increased in those with a bicuspid aortic valve. The diagnosis should be considered in patients with persistent bacteremia, fever, or evidence of conduction system disorders who are being treated with appropriate antibiotic therapy. TEE has a high sensitivity and specificity for identifying perivalvular extension of infection and is the diagnostic study of choice when a perivalvular abscess is suspected.
Cardiac CT has not been extensively studied for use in diagnosing myocardial infection and is not typically used for this purpose. Cardiac magnetic resonance (CMR) imaging, however, is effective in identifying intramyocardial infection, although it is a more complex technology that may have limited availability in some areas. CMR imaging is often used in situations in which a perivalvular abscess is suspected but transesophageal echocardiography is equivocal.
Evidence of a conduction system disorder may be the only indicator of a perivalvular abscess in a patient otherwise responding clinically to treatment for infective endocarditis, as in this patient. Because of the significance of this possible complication, failure to further evaluate conduction system abnormalities in this setting would be inappropriate.
Although transthoracic echocardiography is effective for initial evaluation for endocarditis and assessing for potential complications once endocarditis has been diagnosed (such as valvular or left ventricular dysfunction), TEE is significantly more sensitive for detecting perivalvular abscess because of the closer proximity of the ultrasound probe to the valve structures. It is therefore preferred to transthoracic echocardiography if this diagnosis is a consideration.
- Transesophageal echocardiography is the diagnostic study of choice in patients with a possible perivalvular abscess complicating infective endocarditis.
Correct answer: D. Urgent aortic valve replacement.
The patient should undergo aortic valve replacement now. Although he is hemodynamically stable and does not require pacemaker support, the presence of a new conduction defect confirms extension of the infection into the perivalvular tissues as suggested by echocardiography. When this occurs, the effectiveness of cure with antibiotics alone is decreased significantly, and early surgical intervention is indicated. Other indications for early surgery in native valve infective endocarditis include valve stenosis or regurgitation resulting in heart failure; left-sided endocarditis caused by Staphylococcus aureus, fungal, or other highly resistant organisms; endocarditis complicated by annular or aortic abscess; and endocarditis with persistent bacteremia or fever lasting longer than 5 to 7 days after starting antibiotic therapy. Additionally, early surgery is reasonable in patients with infective endocarditis who have recurrent emboli and persistent vegetations on antibiotic therapy, and may be considered in patients with native valve endocarditis who have mobile vegetations greater than 10 mm in length.
Duration of antibiotic therapy in patients with native valve infective endocarditis is generally 4 to 6 weeks, based upon the specific organism, the site of infection, and any associated complications. Generally, 6-week treatment regimens are used in patients with more virulent or highly resistant organisms and those with cardiac or extracardiac infectious complications. Prolonged treatment for 3 months as therapy for this patient would not be appropriate, even with surgical intervention, and would not be indicated in other patients with native valve endocarditis except in certain situations.
Delaying intervention for 6 weeks of antibiotic therapy or treating with antibiotics alone without surgery would not likely adequately address this patient's endocarditis-related complications. In addition, this approach may result in further decompensation of the patient's clinical status and an increased operative risk for intervention at a later time.
Key to management of patients with infective endocarditis requiring surgery is a multidisciplinary approach involving the internist, cardiologist, infectious disease specialist, and cardiac surgeon.
- The presence of a conduction block is an indication for surgical therapy in patients with native valve infective endocarditis.
Correct answer: D. Remove PICC and add antifungal therapy.
Removal of the peripherally inserted central venous catheter and initiation of antifungal therapy is the most appropriate management in this patient. When candidemia is likely to be the result of an intravenous catheter, the catheter must be removed promptly because it serves as a nidus for ongoing candidemia. The duration is shorter and mortality rate is lower for candidemia related to intravenous catheters when the catheter is removed than when it remains in place. Additionally, catheter salvage is extremely difficult with fungal colonization, almost always requiring removal of the catheter. Although removal of long-term catheters may be a management challenge in patients being treated with a prolonged course of antibiotics, such as this patient, alternative short-term access is indicated to continue treatment and allow antifungal therapy to be given.
Empiric antifungal therapy should be based on the most likely organism (such as Candida albicans) because candidemia can be prolonged and may lead to metastatic complications (endophthalmitis, endocarditis, osteomyelitis) if not already present at the time of diagnosis. Other considerations in choosing empiric therapy include a history of recent azole exposure, prevalence of different species and susceptibility data in a particular institution, the severity of illness, comorbidities (such as neutropenia), and evidence of disseminated involvement (such as the central nervous system or eyes). Some experts recommend an echinocandin as the preferred agent for all patients with candidemia and not just for those who may have recently received an azole or are moderately to severely ill. Blood cultures should always be repeated until candidemia clearance is documented. Treatment should be given for 2 weeks after symptoms resolve and blood cultures are negative for candidemia or longer if metastatic complications are present.
- In patients with candidemia associated with an intravenous catheter, the catheter should be removed and empiric antifungal therapy initiated.
Correct answer: D. Continue current therapy.
The most appropriate management for this patient is to continue current therapy. This patient with methicillin-resistant Staphylococcus aureus endocarditis is found to have worsening kidney function since hospitalization. The differential diagnosis includes infection-related glomerulonephritis (IRGN), drug-induced nephrotoxicity, acute interstitial nephritis (AIN), and septic emboli. The finding of a nephritic urine sediment (erythrocytes, erythrocyte casts, and proteinuria) in an azotemic patient with an active infection suggests IRGN. IRGN is an immune complex–mediated disease most frequently associated with nonstreptococcal infections, with the antigen in the immune complex derived from the infectious agent. Immune complexes deposit in the subepithelial area and activate complement with recruitment of inflammatory cells, leading to a proliferative GN. The likelihood of IRGN is high in this patient given the low C3 complement, the absence of cryoglobulins, and the lack of clinical findings suggestive of other causes on the differential diagnosis.
Glucocorticoids are not typically used in IRGN because there is usually improvement with control of the associated infection.
A kidney biopsy is not indicated because the probability of IRGN is high. However, biopsy would be appropriate if this patient's kidney function fails to improve with treatment of the underlying infection.
Drug-induced tubular toxicity (for example, with vancomycin) typically occurs after 7 to 10 days of antibiotic therapy and the urine sediment does not show cells, unlike in this patient. Antibiotic-induced AIN is typically associated with mild proteinuria, erythrocytes, leukocytes, and leukocyte casts on urinalysis. Eosinophiluria, recurrence of fevers, rash, and peripheral eosinophilia may also be seen and typically occur after 7 to 10 days of therapy, none of which is present in this patient. Therefore, switching vancomycin to daptomycin is not appropriate.
- Management of infection-related glomerulonephritis typically only consists of treatment of the underlying infection.
Correct answer: A. Drug reaction with eosinophilia and systemic symptoms.
This patient most likely has systemic drug hypersensitivity syndrome, otherwise known as drug reaction with eosinophilia and systemic symptoms (DRESS). DRESS is a severe and potentially life-threatening type IV hypersensitivity reaction. Similar to most type IV reactions, onset of the syndrome is delayed, usually occurring 10 days to several weeks after the start of the causative medication. The most common medications that trigger this reaction are sulfonamide antibiotics, allopurinol, and anticonvulsants, but many others have been implicated. In DRESS, patients develop an exanthem rash on the face, trunk, and extremities, and they often have facial edema.
Due to systemic inflammation, patients may have fever, lymphadenopathy, and, in severe reactions, hypotension. When these findings occur in a patient being treated with antibiotics, the systemic inflammatory nature of the reaction may make it difficult to differentiate between a response to an antimicrobial agent or inadequate control of the underlying infection, as in this patient. The treatment of DRESS is to stop the suspected medication immediately, switch to another medication that is unlikely to cross-react, and start systemic glucocorticoids, which can reduce systemic inflammation and lower the risk of end-organ damage.
Morbilliform (meaning measles-like) drug exanthems are the most common pattern of a cutaneous drug reaction. This reaction occurs in up to 8% of hospitalized patients and appears 5 to 15 days after exposure to the causative drug. The characteristic findings include erythematous papules coalescing into plaques, often with some pruritus, and no accompanying systemic symptoms. Facial edema, fever, and laboratory abnormalities are not expected.
Stevens-Johnson syndrome (SJS) is an inflammatory reaction with prominent skin findings that is more commonly triggered by medications than infections. Patients may also have flu-like symptoms, and these may precede the onset of the rash. SJS can be differentiated by the presence of mucosal erosions. Patients with SJS have two or more mucosal sites involved, associated with erythema, pain, and often bloody discharge, none of which this patient has. SJS also has different cutaneous findings including annular erythematous plaques that may have purpuric and eroded centers. These are found on the face, trunk, and extremities including the palms and soles, and involve no more than 10% of the body surface area.
Medications can cause a cutaneous or systemic vasculitis; however, the appearance of this patient's skin findings is not consistent with vasculitis. Purpuric or nonblanching erythematous macules, papules, or plaques are indicative of vasculitis.
- Drug reaction with eosinophilia and systemic symptoms is a systemic drug hypersensitivity reaction that presents with new rash and flu-like symptoms.