eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Endocarditis, Fungal

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Updated: Feb 2, 2009

Introduction

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). Fungal endocarditis 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. Fungal endocarditis may also complicate intracardiac surgery or intrathoracic or systemic fungal infection, particularly in those at highest risk.

Frequency

International

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 fungal endocarditis 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 fungal endocarditis 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

History

• Patients with fungal endocarditis (FE) 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 presents as 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 central venous catheter (CVC) is present. The use of CVC for central hyperalimentation (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 fungal endocarditis.
• Causal organisms include the following:
  • Candida species (two thirds of all reported cases)¹
  • Aspergillus species (particularly in postoperative patients and with spread from systemic and pulmonary infections)²
  • 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
• Fungal endocarditis rarely affects native valves.
• Fungal endocarditis may spread from intrathoracic (particularly pleural-based) infections.

Differential Diagnoses

Other Problems to Be Considered

Intracardiac thrombus
Postoperative cardiac infection
Postoperative wound infection
Pulmonary hypertension
Congenital heart disease

Workup

Laboratory Studies

• In fungal endocarditis (FE), blood cultures may be persistently positive despite therapy, especially with Candida infection. However, culture is often negative; less than one half of candidal endocarditis cases yield positive blood cultures, and other causative organisms are even less frequently identified in blood.
• Culture of urine, sputum, cerebrospinal fluid, synovial fluid, lymph node, and/or bone marrow may offer the only evidence of systemic fungal infection.
• The CBC count may reveal leukocytosis with or without a left shift. Thrombocytopenia may be seen with fungal infections in general in the neonate.
• Erythrocyte sedimentation rates and/or C-reactive protein levels may be elevated, although this is unusual in neonates.
• Urinalysis may demonstrate hematuria, proteinuria, and/or casts.
• Urine for Histoplasma antigen may be positive.

Imaging Studies

• Chest radiography
  • Chest radiography may reveal cardiomegaly.
  • Chest radiography may indicate embolic pulmonary infiltrates or pleural effusions.
• Echocardiography
  • Transthoracic echocardiography is less sensitive than transesophageal echocardiography but is also less invasive.
  • Vegetations and intracardiac thrombi are the most common types but are still rare.
  • Echocardiography may demonstrate pericardial effusion.
  • Normal valves are rarely involved.
  • Echocardiography may suggest myocardial abscesses.
  • Echocardiography may demonstrate associated myocarditis or pericarditis.
• MRI is particularly useful in identifying ring abscesses.

Other Tests

• Fungal smears and cultures of operative specimens
• Electrocardiography is usually nonspecific, although it may demonstrate supraventricular arrhythmias, QRS changes, and/or marked T-wave changes, particularly with myocarditis.

Procedures

• Cardiac catheterization
  • Catheterization may reveal vegetations, thrombi, or underlying cardiac abnormalities.
  • It should be performed with care in the context of active infection.
  • Postcatheterization precautions include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.
  • Complications may include rupture of blood vessel, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.
• Contrast-enhanced central venous catheter (CVC) injection studies may reveal a catheter-associated thrombus.

Histologic Findings

• Biopsy or operative specimens should be cultured and special stains should be used to reveal acute and chronic inflammation and/or fungal elements.

Treatment

Medical Care

• In fungal endocarditis (FE), aggressive antifungal therapy is always necessary but may not prove sufficient to completely alleviate the problem. Removal of the infected nidus is often central to management.
• Provide inotropic support as required.
• Remove the central venous catheter (CVC) when appropriate.
• Decrease immune suppression as much as possible.
• Provide supportive measures.

Surgical Care

• Although a small number of patients have survived with medical therapy alone, most survivors have required both medical and surgical treatment. Operative intervention is almost always required.
• Specific indications include ongoing infection (not fully responsive to medical therapy), embolic phenomena, and cardiac decompensation.
• Delaying operation when specific indications are present is not advantageous.
• Thrombus removal, valve replacement, and abscess resection are the most frequent procedures.
• The occasional neonate with a line-associated candidal infection may not require operative intervention.

Consultations

• Consultation with infectious diseases specialists, cardiologists, and cardiothoracic surgeons is often required.
• Neonatology or critical care consultation should accompany admission to the ICU.

Diet

• As tolerated by the patient's condition and as needed for operative intervention

Activity

• As tolerated by the patient's condition and as needed for operative intervention

Medication

Antifungal antibiotics, frequently used in combination, are the mainstay of treatment of fungal endocarditis (FE). In almost all reported cases of survival, surgical management was necessary to supplement antifungal medical therapy. Studies suggest that fluconazole prophylaxis may help to prevent invasive fungal infections, including endocarditis, in the newborn population.³

Antifungal agents

The mechanism of action may involve increasing the permeability of the cell membrane, which, in turn, causes intracellular components to leak, alteration of RNA and DNA metabolism, or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Amphotericin B (Fungizone, AmBisome, Abelcet)

DOC for severe fungal infections. Fungicidal or fungistatic (depending on the organisms); best-studied drug, despite its toxicities. Although few data are available, use of one of lipid formulations (ie, lipid complex, liposome) at comparable doses is recommended.

Dosing

Adult

Conventional: 0.5-1 mg/kg/d IV q24h
Lipid complex or liposome: 3-5 mg/kg/d IV qd
Relatively high doses of lipid formulations are recommended

Pediatric

Administer as in adults

Interactions

Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cyclosporine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor renal, hepatic, electrolyte, and hematologic status closely; hypercalciuria, hypokalemia, hypomagnesemia, renal tubular acidosis, renal failure, acute hepatic failure, hypotension, and phlebitis may occur; common infusion-related reactions include fever, chills, headache, hypotension, nausea, and vomiting (patient may be given acetaminophen and diphenhydramine 30 min before and 4 h after infusion); meperidine useful for chills; hydrocortisone (1 mg/kg amphotericin B [maximum 25 mg]) added to infusion, may help prevent immediate adverse reactions; salt loading with 10-15 mL/kg of NS infused before each dose may minimize the risk of nephrotoxicity

All these adjunctive measures should be considered only as patient's condition tolerates; adjust dose in renal failure

Flucytosine (Ancobon)

Adjunct to amphotericin B that seems to have a synergistic therapeutic effect in severe fungal infections. Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against candidal and cryptococcal infections and generally used in combination with amphotericin B.

Dosing

Adult

100-150 mg/kg/d PO divided q6h

Pediatric

Administer as in adults

Interactions

Amphotericin B may increase toxicity of flucytosine; cytosine may inactivate flucytosine

Contraindications

Documented hypersensitivity; preexisting thrombocytopenia, GI bleeding, or bone marrow suppression.

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor CBC count and BUN, serum creatinine, alkaline phosphatase, and transaminase levels; common adverse effects include nausea, vomiting, diarrhea, rash, CNS disturbance, anemia, leukopenia, and thrombocytopenia; therapeutic levels are 25-100 mg/L; recommended serum sample at steady state (obtain peak level 2-4 h after PO dose following 4 d of continuous dosing); peak levels of 40-60 mg/L have been recommended for systemic candidiasis; prolonged levels above 100 mg/L can increase risk of bone marrow suppression; GI bleeding in neonates has been reported with serum levels in the 50-60 mg/L range; adjust dose in renal failure

Fluconazole (Diflucan)

Although it has fewer toxicities than the preceding drugs, insufficient data and concerns about efficacy keep fluconazole a second-line drug for this infection.

Dosing

Adult

600-800 mg/d PO/IV
CrCl 21-50 mL/min: Decrease dose 50%
CrCL <20 mL/min: Decrease dose 75%

Pediatric

10-12 mg/kg PO/IV qd
CrCl 21-50 mL/min: Decrease dose 50%
CrCL <20 mL/min: Decrease dose 75%

Interactions

Inhibits CYP450 2C9/10 and CYP450 3A3/4 (weak inhibitor); may increase effects or levels of cyclosporine, phenytoin, theophylline, warfarin, PO hypoglycemics, and AZT; rifampin increases fluconazole metabolism
Cisapride is a CYP450 3A3/4 substrate, fluconazole may decrease elimination and increase risk of arrhythmias

Contraindications

Documented hypersensitivity; concomitant administration with cisapride, terfenadine (recalled from US market), or astemizole (recalled from US market)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose for renal insufficiency; closely monitor if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended for women who are breastfeeding

Caspofungin (Cancidas)

Used to treat refractory invasive aspergillosis and poorly responsive or nonresponsive yeast infections. First of a new class of antifungal drugs (glucan-synthesis inhibitors). Inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell wall.

Dosing

Adult

70 mg IV infused over 1 h on day 1; 50 mg IV qd thereafter

Pediatric

70 mg/m² IV infused over 1 h on day 1; 50 mg/m² qd thereafter

Interactions

Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in moderate hepatic dysfunction (decrease dose); may exacerbate pre-existing renal dysfunction or myelosuppression

Voriconazole (Vfend)

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Posaconazole may become available as a similar, but potentially safer, alternative.

Dosing

Adult

Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h; switch to 200 mg PO q12h when able to tolerate; may increase to 300 mg PO q12h if inadequate response
<40 kg: Average maintenance dose is 100 mg PO q12h (may increase to 150 mg PO q12h)

Pediatric

<12 years:
Not established; limited data suggests:
11 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 6 mg/kg IV q12h infused over 2 h
>12 years: Administer as in adults

Interactions

CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin, phenytoin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, some of which are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG CoA inhibitors, benzodiazepines, calcium channel blockers)

Contraindications

Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (eg, Stevens-Johnson syndrome, phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc

Micafungin (Mycamine)

Member of new class of antifungal agents, echinocandins, which inhibit cell wall synthesis. Inhibits synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells.
Indications include (1) prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation and (2) treatment of esophageal candidiasis.

Dosing

Adult

Candidiasis prophylaxis: 50 mg IV qd infused over 1 h
Esophageal candidiasis: 150 mg IV qd infused over 1 h

Pediatric

Not established; limited data suggests:
Neonates:
<1 kg: 12-16 mg/kg IV qd
>1 kg: 8 mg/kg IV qd
1-7 years: 4 mg/kg IV qd
>8 years: Administer as in adults

Interactions

Increases sirolimus and nifedipine AUC approximately 20%

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects may include headache, nausea, vomiting, and abdominal pain; other adverse effects include skin rash, delirium, phlebitis, shock, leukopenia, and hyperbilirubinemia; rare cases of elevated hepatic enzyme, BUN, and creatine levels have been reported; transient acute intravascular hemolysis and hemoglobinuria may occur; do not mix or infuse in same IV line with other medications because precipitate forms with other commonly used medications (flush existing IV line with 0.9% NaCl before and after infusion); protect from light following dilution

Anidulafungin (Eraxis)

Antifungal agent of the echinocandin class. Inhibits synthesis of 1,3-beta-D-glucan, an essential component of fungal cell walls. Indicated to treat esophageal candidiasis, candidemia, and other forms of candidal infections (eg, intraabdominal abscesses, peritonitis).

Dosing

Adult

Esophageal candidiasis: 100 mg IV on day 1, decrease dose on day 2 and thereafter to 50 mg/d IV
Candidemia and other Candida infections: 200 mg IV on day 1, decrease dose on day 2 and thereafter to 100 mg/d IV
Do not exceed infusion rate of 1.1 mg/min

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include hypokalemia, diarrhea, elevated hepatic enzyme levels, and headache; rare reports of serious hepatotoxicity; infusion related reactions (eg, rash, urticaria, flushing, pruritus, dyspnea, hypotension) may occur, particularly with rapid infusion; following reconstitution, dilute further with D5W or NS before administration

Posaconazole (Noxafil)

Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as PO susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

Dosing

Adult

200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption

Pediatric

<13 years: Not established
>13 years: Administer as in adults

Interactions

Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor
UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk); inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)

Contraindications

Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding

Follow-up

Further Inpatient Care

• Patients with fungal endocarditis (FE) require monitoring in an ICU setting.

Transfer

• Arrange for transfer if the appropriate resources are not locally available.

Complications

• The most common complications in survivors are associated with embolic phenomena, postoperative issues, and underlying or predisposing conditions.

Prognosis

• Prognosis is improving because of advances in intensive and operative care, but the survival rate remains less than 25%.

Patient Education

• Survivors may require subacute bacterial endocarditis prophylaxis, depending on residual cardiac anatomy or abnormalities (see Endocarditis, Bacterial).
• For excellent patient education resources, visit eMedicine's Yeast and Fungal Infections Center. Also, see eMedicine's patient education article Candidiasis (Yeast Infection).

Miscellaneous

Medicolegal Pitfalls

• Failure to consider or to make the diagnosis in the appropriate context
• Failure to diagnose fungal endocarditis (FE) because of negative blood cultures

References

1. Benjamin DK, Miro JM, Hoen B, et al. Candida endocarditis: contemporary cases from the International Collaboration of Infectious Endocarditis Merged Database (ICE-mD). Scand J Infect Dis. 2004;36(6-7):453-5. [Medline].

2. Blum MD, Wiedermann BL. Aspergillus infections. In: Fletcher J, ed. Textbook of Pediatric Infectious Diseases. WB Saunders; 1998:2288-96.

3. Kaufman D, Boyle R, Hazen KC, et al. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med. Dec 6 2001;345(23):1660-6. [Medline].

4. Ankola PA, Perveen S, Fish B. Fungal endocarditis. J Perinatol. Aug 2006;26(8):509-10. [Medline].

5. Baddley JW, Benjamin DK Jr, Patel M, et al. Candida infective endocarditis. Eur J Clin Microbiol Infect Dis. Jul 2008;27(7):519-29. [Medline].

6. Baghaei R, Moghaddam MY, Shahidi M. An unusual right atrial mass in a two-month old infant. Cardiol Young. Dec 2007;17(6):673-4. [Medline].

7. Baltimore RS. Infective endocarditis. In: Pediatric Infectious Diseases: Principles and Practice. 2002:845-56.

8. Divekar A, Rebekya IM, Soni R. Late Onset Candida parapsilosis Endocarditis After Surviving Nosocomial Candidemia in an Infant With Structural Heart Disease. Pediatr Infect Dis J. May 2004;23(5):472-475. [Medline].

9. Ellis ME, Al-Abdely H, Sandridge A, et al. Fungal endocarditis: evidence in the world literature, 1965-1995. Clin Infect Dis. Jan 2001;32(1):50-62. [Medline].

10. Garcia-Teresa MA, Casado-Flores J, Delgado Dominguez MA, et al. Infectious complications of percutaneous central venous catheterization in pediatric patients: a Spanish multicenter study. Intensive Care Med. Mar 2007;33(3):466-76. [Medline].

11. Guzman-Cottrill JA, Zheng X, Chadwick EG. Fusarium solani endocarditis successfully treated with liposomal amphotericin B and voriconazole. Pediatr Infect Dis J. Nov 2004;23(11):1059-61. [Medline].

12. Hallum JL, Williams TW Jr. Candida endocarditis. In: Bodey GP, ed. Candidiasis: Pathogenesis, Diagnosis, and Treatment. 2^nd ed. Lippincott-Raven; 1993:357-69.

13. Hughes WT, Flynn PM. Candidiasis. In: Fletcher J, ed. Textbook of Pediatric Infectious Diseases. 4^th ed. WB Saunders; 1998:2303-13.

14. La Via WV, Koulouri S, Ross LA, et al. Right atrial mass in a child with disseminated coccidioidomycosis. Pediatr Infect Dis J. May 2005;24(5):470-2. [Medline].

15. Levy I, Shalit I, Askenazi S, et al. Duration and outcome of persistent candidaemia in newborn infants. Mycoses. May 2006;49(3):197-201. [Medline].

16. Levy I, Shalit I, Birk E, et al. Candida endocarditis in neonates: report of five cases and review of the literature. Mycoses. Jan 2006;49(1):43-8. [Medline].

17. Luciani GB, Casali G, Viscardi F, et al. Tricuspid valve repair in an infant with multiple obstructive Candida mycetomas. Ann Thorac Surg. Dec 2005;80(6):2378-81. [Medline].

18. Marodi L, Johnston RB Jr. Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms. Curr Opin Pediatr. Dec 2007;19(6):693-7. [Medline].

19. Mayayo E, Moralejo J, Camps J, Guarro J. Fungal endocarditis in premature infants: case report and review. Clin Infect Dis. Feb 1996;22(2):366-8. [Medline].

20. Millar BC, Jugo J, Moore JE. Fungal Endocarditis in Neonates and Children. Pediatr Cardiol. 11 18 2004;[Medline].

21. Moreno-Martinez FL, Lopez FH, Bermudez R, et al. A case report of fungal mitral-valve endocarditis. MedGenMed. Jan 28 2003;5(1):9. [Medline].

22. Mrowczynski W, Wojtalik M. Caspofungin for Candida endocarditis. Pediatr Infect Dis J. Apr 2004;23(4):376. [Medline].

23. Nadir E, Rubinstein E. Fungal Endocarditis. Curr Infect Dis Rep. Aug 2004;6(4):276-282. [Medline].

24. Noyola DE, Fernandez M, Moylett EH, Baker CJ. Ophthalmologic, visceral, and cardiac involvement in neonates with candidemia. Clin Infect Dis. Apr 1 2001;32(7):1018-23. [Medline].

25. Odio CM, Araya R, Pinto LE, et al. Caspofungin therapy of neonates with invasive candidiasis. Pediatr Infect Dis J. Dec 2004;23(12):1093-7. [Medline].

26. Overturf GD. Focal bacterial infections. In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant. 6^th ed. WB Saunders; 2006:347-84.

27. Ozkiraz S, Tarcan A, Gokmen Z, et al. Invasive Candida albicans infection mimicking leukemia in a neonate. J Matern Fetal Neonatal Med. Jul 2007;20(7):555-7. [Medline].

28. Pai MP, Samples ML, Mercier RC, Spilde MN. Activities and ultrastructural effects of antifungal combinations against simulated Candida endocardial vegetations. Antimicrob Agents Chemother. Jul 2008;52(7):2367-76. [Medline].

29. Robertson J, Shilkofski N. Drug doses. In: The Harriet Lane Handbook: A Manual for Pediatric House Officers. Philadelphia, PA: Mosby; 2005:679-1009.

30. Rodriguez D, Almirante B, Park BJ, et al. Candidemia in neonatal intensive care units: Barcelona, Spain. Pediatr Infect Dis J. Mar 2006;25(3):224-9. [Medline].

31. Sanchez PJ, Siegel JD, Fishbein J. Candida endocarditis: successful medical management in three preterm infants and review of the literature. Pediatr Infect Dis J. Mar 1991;10(3):239-43. [Medline].

32. Starke JR. Infective endocarditis. In: Fletcher J, ed. Textbook of Pediatric Infectious Diseases. 4^th ed. WB Saunders; 1998:315-38.

33. Steinbach WJ, Benjamin DK. New antifungal agents under development in children and neonates. Curr Opin Infect Dis. Dec 2005;18(6):484-9. [Medline].

34. Steinbach WJ, Perfect JR, Cabell CH, et al. A meta-analysis of medical versus surgical therapy for Candida endocarditis. J Infect. Oct 2005;51(3):230-47. [Medline].

35. Tissières P, Jaeggi ET, Beghetti M, Gervaix A. Increase of fungal endocarditis in children. Infection. Aug 2005;33(4):267-72. [Medline].

36. Tolan RW, Kleiman MB, Frank M, et al. Operative intervention in active endocarditis in children: report of a series of cases and review. Clin Infect Dis. Apr 1992;14(4):852-62. [Medline].

37. Varghese GM, Sobel JD. Fungal endocarditis. Curr Infect Dis Rep. Jul 2008;10(4):275-9. [Medline].

38. Weinstein L, Brusch JL. Microbiology of infective endocarditis and clinical correlates: gram-negative and other organisms. In: Infective Endocarditis. Oxford University Press; 1996:73-122.

39. Weinstein L, Brusch JL. Pediatric endocarditis. In: Infective Endocarditis. Oxford University Press;1996:229-35.

40. Wertz KK, Pretzlaff RK. Caspofungin in a pediatric patient with persistent candidemia. Pediatr Crit Care Med. Mar 2004;5(2):181-3. [Medline].

Keywords

fungal endocarditis, FE, arthritis, Aspergillus, bacterial endocarditis, Blastomyces dermatitidis, Candida, candidal endocarditis, candidal infection, cardiac infection, central hyperalimentation, CHA, Coccidioides immitis, Cryptococcus neoformans, disseminated candidal infection, fever, fungal infection, Fusarium, heart murmur, Histoplasma capsulatum, infectious endocarditis, Janeway lesions, Mucor, neonatal sepsis, Osler nodes, overwhelming infection, petechiae, Pseudallescheria boydii, Roth spots, splenomegaly, splinter hemorrhages, superior vena cava syndrome, Torulopsis galbrata, Trichosporon beigelii, weight loss

Contributor Information and Disclosures

Author

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Medical Editor

Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA, Professor, Departments of Pediatrics (Cardiology), Cardiovascular Sciences, and Molecular and Human Genetics, Baylor College of Medicine; Chief of Pediatric Cardiology, Foundation Chair in Pediatric Cardiac Research, Texas Children's Hospital
Jeffrey Allen Towbin, MD, MSc, FAAP, FACC, FAHA is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Cardiology, American College of Sports Medicine, American Heart Association, American Medical Association, American Society of Human Genetics, Cardiac Electrophysiology Society, Heart Rhythm Society, New York Academy of Sciences, Society for Pediatric Research, Texas Medical Association, and Texas Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine
Steven R Neish, MD, SM is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Heart Association
Disclosure: Nothing to disclose.

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