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Fatal Staphylococcus Aureus Endocarditis Misdiagnosed as Multisystem Inflammatory Syndrome in Children

Peña-Moreno, Ana MD*; Torres-Soblechero, Laura MD*; López-Blázquez, María MD; Butragueño-Laiseca, Laura MD

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The Pediatric Infectious Disease Journal: February 2022 - Volume 41 - Issue 2 - p e58-e59
doi: 10.1097/INF.0000000000003417
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Abstract

Infective endocarditis (IE) is a rare entity in children with an incidence of 0.05–0.12 cases per 1000 admissions.1 Only 8%–10% of these pediatric cases affect previously healthy children without an identifiable risk factor such as congenital heart disease. In previously healthy children, IE usually affects the left heart valves and the most frequent etiology is Staphylococcus aureus bacteremia.1

CASE REPORT

A previously healthy 10-year-old male was admitted to hospital with a 6-day history of fever, headache, abdominal pain, vomiting and fingertip pain. Physical examination revealed a generally unwell-looking, pale and tachycardic child. Blood tests showed anemia, thrombocytopenia, leukocytosis with lymphopenia, positive acute phase reactants (C-reactive protein 24.9 mg/dL and procalcitonin 9.1 ng/mL), high troponin level (105 ng/L), N-terminal pro-B-type natriuretic peptide (3338 pg/mL) and d-dimer (20,486 ng/mL). Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 was the initial suspected diagnosis, even though the results of severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction and serology were later negative. An echocardiogram was performed that showed an echogenic lesion on the mitral valve. Treatment with vancomycin and gentamicin was started for the diagnosis of IE. Methicillin-sensitive S. aureus was identified in blood cultures; therefore, antibiotic treatment was changed to cloxacillin. Purpuric lesions on the fingertips and toes appeared (Fig. 1A). A thoracic computed tomography (CT) scan did not show pulmonary thromboembolism and the abdominal CT scan revealed hepatic, splenic and renal artery embolism. Due to progression of the mitral regurgitation, the patient was transferred to our hospital.

F1
FIGURE 1.:
A: Skin manifestations of bacterial endocarditis. Janeway lesions and Osler nodes. B: Brain CT scan. Septic microembolism with hemorrhagic component located on corticosubcortical region of left frontal lobe.

When he arrived, he was tachycardic and pale with normal blood pressure. An echocardiogram showed vegetations of 16 × 13 mm and 12 × 10 mm in both leaflets of the ventricular side mitral valve with moderate to severe regurgitation (Fig. 2). Fever and positive blood cultures were persistent. A brain CT scan was performed, showing septic microembolism with a hemorrhagic component, located on the corticosubcortical region of the left frontal lobe (Fig. 1B), right parietal lobe and right perisylvian region. The thoracic and abdominal CT scans were repeated, with similar findings to the previous studies.

F2
FIGURE 2.:
Echocardiogram images. A: Vegetations in both leaflets of the left side ventricular mitral valve. B: Moderate mitral regurgitation (vena contracta).

Because of the high-risk of systemic embolism, urgent surgery was indicated. Vegetations were surgically removed under cardiopulmonary bypass; valvuloplasty was not effective due to severe, persistent mitral regurgitation, so the valve was replaced with a mechanical valve. Bispectral index monitor and noninvasive cerebral oximetry readings remained reassuring throughout the procedure. However, anisocoria with right mydriasis was noticed on arrival to pediatric intensive care unit. A brain CT scan was performed, showing a left frontal lobe hematoma with intraventricular extension. The patient showed clinical signs of intracranial hypertension, so specific treatment was initiated. Nevertheless, the mydriasis became bilateral and bispectral index value decreased with a high suppression ratio. Two hours later, a second brain CT scan was performed, showing diffuse cerebral edema and an incipient middle cerebral artery stroke.

Intracranial pressure was monitored with values up to 90 mm Hg despite optimal intracranial hypertension medical treatment. Decompressive craniectomy was dismissed due to the severity of the brain lesions. The patient continued to deteriorate with the development of brainstem death signs, so the decision was made to withdraw life-sustaining therapy. The patient died 24 hours after surgery.

DISCUSSION

In previously healthy children, the diagnosis and treatment of IE is challenging. This diagnostic difficulty together with the current epidemiologic context led to an initial misdiagnosis of pediatric multisystem inflammatory syndrome temporally associated with coronavirus disease 2019.

Clinical manifestations of left IE include symptoms related to (valvular insufficiency or stenosis, cardiac conduction defects and heart failure), symptoms related to embolic phenomena and immunologic vascular phenomena. Emboli in left IE can affect the kidneys, liver, spleen, coronary arteries and central nervous system. Systemic emboli are especially frequent in left IE caused by S. aureus; neurologic complications are found in 43.3%, being associated with worse outcomes.2 Further investigations with thoracoabdominal and cerebral tomography should be performed.3

The need for surgery should be assessed on an individual basis. The main guidelines on the of IE include the need for surgery in the case of: left IE caused by S. aureus, fungi or resistant microorganisms, persistent bacteremia, persistent vegetations with embolic phenomena, significant valvular insufficiency and extension with valve dehiscence, heart block or abscess.3 Early surgery in cases with high-risk of systemic embolism improves the prognosis, although indications for surgery should be individually assessed for each case.

The prognosis of IE has improved in recent years, with a mortality rate of 5%–10%1 that is even lower in previously healthy children. The clinical course after surgery is usually favorable, although there are some risk factors that increase the probability of neurologic events, with a 6% incidence of cerebral stroke in pediatric patients.1,4 Our patient met the criteria for surgery following the updated guidelines. The presence of intracranial hemorrhages contraindicates early surgery3 but recent studies have found that microbleeds (defined as lesions ≤ 10 mm) do not increase the risk of hemorrhagic stroke or the overall global mortality risk.5–8 Following this evidence, the European guidelines9 do not recommend delaying surgery because of the presence of microbleeds. Although the clinical course seen in our patient is fortunately uncommon, it must be taken into account as a possible complication of IE. A possible hypothesis is that neurologic damage could have happened in the context of new septic emboli during surgery with progression of the vasogenic edema surrounding the septic microstrokes already present. In these patients, the risk of bleeding increases when they need cardiopulmonary bypass and anticoagulation for valvular surgery. Neurologic monitoring before, during and after the operative period is crucial to detect complications.

REFERENCES

1. Baltimore RS, Gewitz M, Baddour LM, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132:1487–1515.
2. García-Cabrera E, Fernández-Hidalgo N, Almirante B, et al.; Group for the Study of Cardiovascular Infections of the Andalusian Society of Infectious Diseases; Spanish Network for Research in Infectious Diseases. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study. Circulation. 2013;127:2272–2284.
3. Pettersson GB, Hussain ST. Current AATS guidelines on surgical treatment of infective endocarditis. Ann Cardiothorac Surg. 2019;8:630–644.
4. Venkatesan C, Wainwright MS. Pediatric endocarditis and stroke: a single-center retrospective review of seven cases. Pediatr Neurol. 2008;38:243–247.
5. Kim DY, Kim HW, Jo KH. Neurologic outcomes after early surgery for infective endocarditis in patients with combined cerebral septic embolism. Interact Cardiovasc Thorac Surg. 2017;24:521–526.
6. Murai R, Kaji S, Kitai T, et al. The clinical significance of cerebral microbleeds in infective endocarditis patients. Semin Thorac Cardiovasc Surg. 2019;31:51–58.
7. Venn RA, Ning M, Vlahakes GJ, et al. Surgical timing in infective endocarditis complicated by intracranial hemorrhage. Am Heart J. 2019;216:102–112.
8. Carneiro TS, Awtry E, Dobrilovic N, et al. Neurological complications of endocarditis: a multidisciplinay review with focus on surgical decision making. Semin Neurol. 2019;39:495506.
9. Habib G, Lancellotti P, Antunes MJ, et al. 2015ESC guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). EurHear J. 2015;36:30753128.
Keywords:

infective endocarditis; valvular surgery; multisystem inflammatory syndrome; coronavirus disease 2019; cerebral microbleeds; stroke; Staphylococcus aureus

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