INTRODUCTION	Section 2 of 10
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Background: Fungal endocarditis (FE) remains a rare infection, although its incidence is increasing because more neonates are in intensive care and more neonates are undergoing cardiac surgical procedures and central hyperalimentation (CHA). It rarely affects native valves and occurs most frequently in neonates as part of a disseminated fungal infection, in patients following cardiac surgery, or in those who develop an intracardiac thrombus or valvular injury due to a central venous catheter (CVC). FE is often difficult to diagnose because the presentation may be nonspecific and the disease typically occurs in otherwise critically ill patients with confusing clinical pictures.

Pathophysiology: Approximately one fourth of neonates and children with systemic candidal disease have a demonstrable cardiac lesion. Fungal infection usually occurs in a right-sided intracardiac thrombus or at the site of a valvular injury secondary to a CVC. FE may also complicate intracardiac surgery or intrathoracic or systemic fungal infection, particularly in those at highest risk.

Frequency:

• Internationally: Fungi cause 0-12% (average 1.1%) of infectious endocarditis cases in children worldwide. Thus, the incidence rate is approximately 1.5-4 cases per 10 million children. Most published series are from the United States and other developed countries. Two thirds of FE is candidal. Among those in the neonatal intensive care unit (NICU), 1% develop disseminated candidal infection. Despite recent rises in frequency, this remains a rare infection, with reported cases numbering less than a few hundred in patients of any age.

  Data are too limited to document the incidence of FE in the developing world. As many risk factors for the disease are associated with advanced medical care, a direct relationship between the availability of these technologies and the frequency of this infection is likely present.

Mortality/Morbidity: The mortality rate remains 75-90% because of difficulty in making the diagnosis, lack of effective antifungal antibiotics, need for surgical intervention in most cases, presence of underlying or predisposing conditions, and frequent comorbid conditions in these typically critically ill neonates and children.

Race: No racial predisposition is present.

Sex: A slight male predominance is observed.

Age: Increasingly, the age distribution of cases is bimodal. The number of cases reported is rising in neonates and, gradually with age, in adults in their second decade of life.

	CLINICAL	Section 3 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History:

• Patients may have a history of cardiac surgery complicated by symptoms of infection, such as fever, deteriorating cardiac status, embolic phenomena, and dehiscence.

• History of intrathoracic or systemic fungal infection with spread to the heart is rare.

Physical:

• On rare occasions, fungal endocarditis (FE) manifests similar to typical bacterial endocarditis, with fever, weight loss, splenomegaly, splinter hemorrhages, Roth spots (pale retinal lesions with surrounding hemorrhage), Osler nodes (painful nodular lesions on the finger and/or toe pads), petechiae, Janeway lesions (painless hemorrhagic plaques on the palms and/or soles), arthritis, and a new or changing heart murmur.

• Often, an indwelling CVC is present. The use of CVC for CHA is an additional risk factor.

• Occasionally, positive blood culture results or positive culture results of other tissues and fluids (despite negative blood culture results) are the only evidence.

• Cardiac involvement, without other symptoms or signs of infection, may be the only clinically apparent feature.

• An inflow obstruction (superior vena cava syndrome with cough, hoarseness, dysphagia, and/or a full sensation in the ears) due to an infected thrombus may be the sole manifestation of disease.

• In neonates, symptoms are often nonspecific and include apnea and bradycardia, hypothermia, poor perfusion, feeding intolerance, increased ventilatory support, and evidence of septic emboli. Rarely, a new or changing heart murmur is present.

• In neonates, Janeway lesions, petechiae, splinter hemorrhages, and evidence of multiple septic emboli have been reported, although Osler nodes and Roth spots have not been reported.

• In the postoperative period, patients may have symptoms such as fever, cardiac decompensation, a new or changing heart murmur, evidence of embolic phenomena, and dehiscence.

• Superior vena cava syndrome may manifest as hoarseness, swelling of the face, wheezing or stridor, and/or venous engorgement.

Causes:

• No particular inheritance patterns are associated with FE.

• Causal organisms include the following:

• Candida species (two thirds of all reported cases)

• Aspergillus species (particularly in postoperative patients and with spread from systemic and pulmonary infections)

• Histoplasma capsulatum (causes pericarditis more frequently)

• Blastomyces dermatitidis, Cryptococcus neoformans, Coccidioides immitis (mostly pericarditis; rarely endocarditis)

• Mucor species, Torulopsis glabrata, Trichosporon beigelii, Fusarium species (rare)

• Pseudallescheria boydii (prosthetic valve endocarditis)

• Risk factors include the following:

• Neonatal period

• History of cardiac surgery

• CVC in place

• CHA

• Broad-spectrum antibacterial therapy

• Intravenous drug use

• Preexisting valvular lesion or injury, such as congenital heart disease, bacterial endocarditis, rheumatic heart disease, prosthetic valve

• Transient fungemia after bowel surgery

• Any condition associated with immune compromise

• FE rarely affects native valves.

• FE may spread from intrathoracic (particularly pleural-based) infections.