Management of Pediatric Candida Endocarditis: A Mini Review on Available Literature Between 2010-2022
-
Mohamad Rafie Khurgami
,
Fariba Shirvani
,
Zeynab Yasin
,
Maryam Fattahi
,
Pegah Tamimi
,
Aliasghar Ghaderi
,
Mahsa Fattahi
Abstract
There has been a notable rise in cases of Candida Endocarditis (CE). Even with surgical procedures and antifungal treatments, the worldwide impact of Candida on health, including morbidity and mortality, has escalated. This narrative review was carried out through the PubMed and Scopus databases, where the search terms “Candida” and “Endocarditis” were used. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, reviews, and case reports. The search was restricted to articles written in the English language from 2010 to Dec 30, 2022. Moreover, duplicate articles and non-available full-text articles were excluded. The extracted data of the search results were retrieved in this study. A background involving central venous catheters (CVC), congenital heart conditions and persistent debilitating illnesses heightens the chances of infection. Early initiation of antifungal treatment is crucial when considering Candida species and associated risk factors. The majority of research has concentrated on adult populations, leaving a gap in studies concerning pediatric patients. Presents manuscript review pediatric CE, including recent advances in management.
1. Kara A, Devrim I, Mese T, Bayram N, Yilmazer M, Gulfidan G. The frequency of infective endocarditis in Candida bloodstream infections: a retrospective study in a child hospital. Braz J Cardiovasc Surg 2018;33:54-8.
2. Kumar P, Muranjan MN, Tullu MS, Vaideeswar P, Kher A, Lahiri KR. Candida tropicalis endocarditis: Treatment in a resource-poor setting. Ann Pediatr Cardiol 2010;3:174-7.
3. Collins F, Wenlock RD, Curtis S, Hyde J, James PR. Fungal endocarditis after type A dissection, a positive outcome from Candida parapsilosis prosthetic aortic valve endocarditis and aortic graft infection: A testament to multidisciplinary practice. Clin Infect Dis 2021;12:100-6.
4. Otto CM, Bonow RO. Valvular heart disease: A companion to Braunwald's heart disease E-Book. Elsevier Health Sciences; 2009.
5. Pyrgos V, Ratanavanich K, Donegan N, Veis J, Walsh TJ, Shoham S. Candida bloodstream infections in hemodialysis recipients. Sabouraudia 2009;47:463-7.
6. De Rosa FG, D'Avolio A, Corcione S, Baietto L, Raviolo S, Centofanti P, et al. Anidulafungin for Candida glabrata infective endocarditis. Antimicrob Agents Chemother 2012;56:4552-3.
7. Brajtburg J, Powderly W, Kobayashi GS, Medoff G. Amphotericin B: current understanding of mechanisms of action. Antimicrob Agents Chemother 1990;34:183-8.
8. Watamoto T, Samaranayake L, Egusa H, Yatani H, Seneviratne C. Transcriptional regulation of drug-resistance genes in Candida albicans biofilms in response to antifungals. J Med Microbiol 2011;60:1241-7.
9. Faustino C, Pinheiro L. Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy. Pharmaceutics 2020;12.
10. Nett JE, Andes DR. Antifungals: Drug class, mechanisms of action, pharmacokinetics/pharmacodynamics, drug-drug Interactions, toxicity, and clinical use. Candida Candidiasis 2011:343-71.
11. Parente-Rocha JA, Bailão AM, Amaral AC, Taborda CP, Paccez JD, Borges CL, et al. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi. Mediators Inflamm 2017;2017:9870679.
12. Sigera LSM, Denning DW. Flucytosine and its clinical usage. Therapeutic Adv Infect Dis 2023;10:20499361231161387.
13. Bidaud AL, Botterel F, Chowdhary A, Dannaoui E. In vitro antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against Candida auris shows no antagonism. Antimicrob Agents Chemother 2019;63:12.
14. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-e50.
15. Stripeli F, Tsolia M, Trapali C, Papaevangelou V, Vlachos E, Pasparakis D, et al. Successful medical treatment of Candida endocarditis with liposomal amphotericin B without surgical intervention. Eur J Pediatr 2008;167:469-70.
16. Bezerra LS, Silva JAD, Santos-Veloso MAO, Lima SG, Chaves-Markman  V, Jucá MB. Antifungal Efficacy of Amphotericin B in Candida Albicans Endocarditis Therapy: Systematic Review. Braz J Cardiovasc Surg 2020;35:789-96.
17. Anil Kumar V, Francis E, Sreehari S, Raj B. Tricuspid valve mycetoma in an infant successfully treated by excision and complex tricuspid valve repair followed by fluconazole therapy. Surg Inf 2014;15:134-40.
18. Babayigit A, Cebeci B, Buyukkale G, Semerci SY, Bornaun H, Oztarhan K, et al. Treatment of neonatal fungal infective endocarditis with recombinant tissue plasminogen activator in a low birth weight infant case report and review of the literature. Mycoses 2015;58:578-81.
19. Marks KA, Zucker N, Kapelushnik J, Karplus M, Levitas A. Infective endocarditis successfully treated in extremely low birth weight infants with recombinant tissue plasminogen activator. Pediatrics 2002;109:153-8.
20. Aydemir C, Erdeve O, Oguz SS, Altug N, Dilmen U. Successful treatment of Candida albicans endocarditis vegetations with recombinant tissue plasminogen activator in an extremely low birth weight preterm infant. Mycoses 2011;54:e590-2.
21. Ozdemir AA. Recombinant tissue plasminogen activator treatment for intracardiac vegetation in a very low birth weight infant. Arch Argent Pediatr 2017;115:e307-e10.
22. Ozturk E, Tanidir IC, Guzeltas A, Haydin S. Surgical Treatment of Giant Candida albicans Vegetation of Tricuspid Valve Endocarditis in a Preterm Baby. Pediatrics Neonatol 2015;56:197-9.
23. Lee Y, Puumala E, Robbins N, Cowen LE. Antifungal drug resistance: molecular mechanisms in Candida albicans and beyond. Chem Rev 2020;121:3390-411.
24. Klepser ME. Antifungal resistance among Candida species. Pharmacotherapy 2001;21:124S-32S.
25. Beardsley J, Halliday CL, Chen SC, Sorrell TC. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside. Future Microbiol 2018;13:1175-91.
26. Schwartz IS, Patterson TF. The emerging threat of antifungal resistance in transplant infectious diseases. Curr Infect Dis Rep 2018;20:1-10.
27. Morio F, Jensen RH, Le Pape P, Arendrup MC. Molecular basis of antifungal drug resistance in yeasts. Int J Antimicrob Agents 2017;50:599-606.
28. Ramage G, VandeWalle K, Bachmann SP, Wickes BL, López-Ribot JL. In vitro pharmacodynamic properties of three antifungal agents against preformed Candida albicans biofilms determined by time-kill studies. Antimicrob Agents Chemother 2002;46:3634-6
29. Uppuluri P, Srinivasan A, Ramasubramanian A, Lopez-Ribot JL. Effects of fluconazole, amphotericin B, and caspofungin on Candida albicans biofilms under conditions of flow and on biofilm dispersion. Antimicrob Agents Chemother 2011;55:3591-3.
30. Kuhn D, George T, Chandra J, Mukherjee P, Ghannoum M. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002;46:1773-80.
31. Mukherjee PK, Long L, Kim HG, Ghannoum MA. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents 2009;33:149-53.
32. Katragkou A, Chatzimoschou A, Simitsopoulou M, Dalakiouridou M, Diza-Mataftsi E, Tsantali C, et al. Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms. Antimicrob Agents Chemother 2008;52:357-60.
33. Cocuaud C, Rodier M-H, Daniault G, Imbert C. Anti-metabolic activity of caspofungin against Candida albicans and Candida parapsilosis biofilms. J Antimicrob Chemother 2005;56:507-12.
34. Ammannaya GKK N S. Fungal endocarditis in children and antifungal prophylaxis: Author’s reply. Kardiol Pol 2020;78:91-2.
35. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F, et al. 2015 ESC 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 European Association of Nuclear Medicine EANM. Eur Heart J 2015;36:3075-128.
36. Agin H, Devrim I, Isguder R, Karaarslan U, Kanik E, Gunay I, et al. Risk Factors for Candidemia in Pediatric Intensive Care Unit Patients. Indian J Pediatr 2014;81:1158-62.
37. Vaideeswar P. Candidial Endocarditis: A Single-Institute Pathological Analysis. Mycopathologia 2015;180:81-7.
38. Martínez PA, Guerrero M, Santos J, Hernández MS, Mercado MC. [Pediatric clinical experience in infectious endocarditis due to Candida spp]. Rev Chilena Infectol 2018;35:553-9.
39. Azhar A. Successful management of fungal pericarditis and endocarditis in a neonate: A case report. J Saudi Heart Assoc 2012;24:195-9.
40. Jajoo M, Kumar V, Goyal VK, Garg A. Candida tropicalis infection in a term neonate with gall bladder masses and infective endocarditis. Asian Pac J Trop Med 2012;5:410-2.
41. Cetin M, Ozen S, Yildirimer M, Deveci M, Coskun S, Kizilkaya M. Premature newborn with intracardiac fungus balls and endocarditis which is curable only with antifungal therapy: case presentation. Clin Med Case Rep 2013;2:315-7.
42. Chaudhary N, Vishwanath M, Pahuja M, Borker A. Candida albicans endocarditis in a child with acute lymphoblastic leukemia: a dreaded complication of intensive chemotherapy. Indian J Med Paediatr Oncol 2013;34:28-30.
43. Ozdemir AA, Oral TK, Varol A. Fungal endocarditis in an extremely low birth weight infant: case report. Arch Argent Pediatr 2016;114:e117-20.
44. Oner T, Korun O, Celebi A. Rare presentation of Candida albicans: infective endocarditis and a pulmonary coin lesion. Cardiol Young 2018;28:602-4.
45. Babazadeh A, Ebrahimpour S, Taghi-Salehi-Omran M, Ahangar-Darabi Z, Karkhah A, Hamid-Abedi S, et al. Mitral-valve endocarditis due to Candida albicans: A case report. Acta Fac Med Naissensis 2018;35:345-50.
46. Vanhie ES, Bogers AJ, Helbing WA. Long-term outcome after tricuspid valvectomy in a neonate with Candida endocarditis: a case report. Cardiol Young 2019;29:528-30.
47. Portillo-Miño JD, Cerón-Muñoz E, Toro-Zapata C, Chaucanez-Bastidas Y. Endocarditis infecciosa debida a candida lusitaniae en un lactante menor: Reporte de caso. Infectio 2020;266-70
48. Prasad Gourav K, Mandal B, Mishra A, Narayanan Nayanar V. Successful medical management of fungal infective endocarditis post VSD closure. Ann Card Anaesth 2021;24:95-8.
49. Salehi S, Radvar M, Askari B. Candida albicans Endocarditis in a Child With Acute Lymphoblastic Leukemia: A Rare Case Report. Iran Heart J 2022;23:220-2.
50. Vassileva Z. Mitral valve replacement in a 3.9-kg infant with fungal endocarditis: A case report. Turk Gogus Kalp Damar Cerrahisi Derg 2022;30.
2. Kumar P, Muranjan MN, Tullu MS, Vaideeswar P, Kher A, Lahiri KR. Candida tropicalis endocarditis: Treatment in a resource-poor setting. Ann Pediatr Cardiol 2010;3:174-7.
3. Collins F, Wenlock RD, Curtis S, Hyde J, James PR. Fungal endocarditis after type A dissection, a positive outcome from Candida parapsilosis prosthetic aortic valve endocarditis and aortic graft infection: A testament to multidisciplinary practice. Clin Infect Dis 2021;12:100-6.
4. Otto CM, Bonow RO. Valvular heart disease: A companion to Braunwald's heart disease E-Book. Elsevier Health Sciences; 2009.
5. Pyrgos V, Ratanavanich K, Donegan N, Veis J, Walsh TJ, Shoham S. Candida bloodstream infections in hemodialysis recipients. Sabouraudia 2009;47:463-7.
6. De Rosa FG, D'Avolio A, Corcione S, Baietto L, Raviolo S, Centofanti P, et al. Anidulafungin for Candida glabrata infective endocarditis. Antimicrob Agents Chemother 2012;56:4552-3.
7. Brajtburg J, Powderly W, Kobayashi GS, Medoff G. Amphotericin B: current understanding of mechanisms of action. Antimicrob Agents Chemother 1990;34:183-8.
8. Watamoto T, Samaranayake L, Egusa H, Yatani H, Seneviratne C. Transcriptional regulation of drug-resistance genes in Candida albicans biofilms in response to antifungals. J Med Microbiol 2011;60:1241-7.
9. Faustino C, Pinheiro L. Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy. Pharmaceutics 2020;12.
10. Nett JE, Andes DR. Antifungals: Drug class, mechanisms of action, pharmacokinetics/pharmacodynamics, drug-drug Interactions, toxicity, and clinical use. Candida Candidiasis 2011:343-71.
11. Parente-Rocha JA, Bailão AM, Amaral AC, Taborda CP, Paccez JD, Borges CL, et al. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi. Mediators Inflamm 2017;2017:9870679.
12. Sigera LSM, Denning DW. Flucytosine and its clinical usage. Therapeutic Adv Infect Dis 2023;10:20499361231161387.
13. Bidaud AL, Botterel F, Chowdhary A, Dannaoui E. In vitro antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against Candida auris shows no antagonism. Antimicrob Agents Chemother 2019;63:12.
14. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:e1-e50.
15. Stripeli F, Tsolia M, Trapali C, Papaevangelou V, Vlachos E, Pasparakis D, et al. Successful medical treatment of Candida endocarditis with liposomal amphotericin B without surgical intervention. Eur J Pediatr 2008;167:469-70.
16. Bezerra LS, Silva JAD, Santos-Veloso MAO, Lima SG, Chaves-Markman  V, Jucá MB. Antifungal Efficacy of Amphotericin B in Candida Albicans Endocarditis Therapy: Systematic Review. Braz J Cardiovasc Surg 2020;35:789-96.
17. Anil Kumar V, Francis E, Sreehari S, Raj B. Tricuspid valve mycetoma in an infant successfully treated by excision and complex tricuspid valve repair followed by fluconazole therapy. Surg Inf 2014;15:134-40.
18. Babayigit A, Cebeci B, Buyukkale G, Semerci SY, Bornaun H, Oztarhan K, et al. Treatment of neonatal fungal infective endocarditis with recombinant tissue plasminogen activator in a low birth weight infant case report and review of the literature. Mycoses 2015;58:578-81.
19. Marks KA, Zucker N, Kapelushnik J, Karplus M, Levitas A. Infective endocarditis successfully treated in extremely low birth weight infants with recombinant tissue plasminogen activator. Pediatrics 2002;109:153-8.
20. Aydemir C, Erdeve O, Oguz SS, Altug N, Dilmen U. Successful treatment of Candida albicans endocarditis vegetations with recombinant tissue plasminogen activator in an extremely low birth weight preterm infant. Mycoses 2011;54:e590-2.
21. Ozdemir AA. Recombinant tissue plasminogen activator treatment for intracardiac vegetation in a very low birth weight infant. Arch Argent Pediatr 2017;115:e307-e10.
22. Ozturk E, Tanidir IC, Guzeltas A, Haydin S. Surgical Treatment of Giant Candida albicans Vegetation of Tricuspid Valve Endocarditis in a Preterm Baby. Pediatrics Neonatol 2015;56:197-9.
23. Lee Y, Puumala E, Robbins N, Cowen LE. Antifungal drug resistance: molecular mechanisms in Candida albicans and beyond. Chem Rev 2020;121:3390-411.
24. Klepser ME. Antifungal resistance among Candida species. Pharmacotherapy 2001;21:124S-32S.
25. Beardsley J, Halliday CL, Chen SC, Sorrell TC. Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside. Future Microbiol 2018;13:1175-91.
26. Schwartz IS, Patterson TF. The emerging threat of antifungal resistance in transplant infectious diseases. Curr Infect Dis Rep 2018;20:1-10.
27. Morio F, Jensen RH, Le Pape P, Arendrup MC. Molecular basis of antifungal drug resistance in yeasts. Int J Antimicrob Agents 2017;50:599-606.
28. Ramage G, VandeWalle K, Bachmann SP, Wickes BL, López-Ribot JL. In vitro pharmacodynamic properties of three antifungal agents against preformed Candida albicans biofilms determined by time-kill studies. Antimicrob Agents Chemother 2002;46:3634-6
29. Uppuluri P, Srinivasan A, Ramasubramanian A, Lopez-Ribot JL. Effects of fluconazole, amphotericin B, and caspofungin on Candida albicans biofilms under conditions of flow and on biofilm dispersion. Antimicrob Agents Chemother 2011;55:3591-3.
30. Kuhn D, George T, Chandra J, Mukherjee P, Ghannoum M. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 2002;46:1773-80.
31. Mukherjee PK, Long L, Kim HG, Ghannoum MA. Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents 2009;33:149-53.
32. Katragkou A, Chatzimoschou A, Simitsopoulou M, Dalakiouridou M, Diza-Mataftsi E, Tsantali C, et al. Differential activities of newer antifungal agents against Candida albicans and Candida parapsilosis biofilms. Antimicrob Agents Chemother 2008;52:357-60.
33. Cocuaud C, Rodier M-H, Daniault G, Imbert C. Anti-metabolic activity of caspofungin against Candida albicans and Candida parapsilosis biofilms. J Antimicrob Chemother 2005;56:507-12.
34. Ammannaya GKK N S. Fungal endocarditis in children and antifungal prophylaxis: Author’s reply. Kardiol Pol 2020;78:91-2.
35. Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F, et al. 2015 ESC 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 European Association of Nuclear Medicine EANM. Eur Heart J 2015;36:3075-128.
36. Agin H, Devrim I, Isguder R, Karaarslan U, Kanik E, Gunay I, et al. Risk Factors for Candidemia in Pediatric Intensive Care Unit Patients. Indian J Pediatr 2014;81:1158-62.
37. Vaideeswar P. Candidial Endocarditis: A Single-Institute Pathological Analysis. Mycopathologia 2015;180:81-7.
38. Martínez PA, Guerrero M, Santos J, Hernández MS, Mercado MC. [Pediatric clinical experience in infectious endocarditis due to Candida spp]. Rev Chilena Infectol 2018;35:553-9.
39. Azhar A. Successful management of fungal pericarditis and endocarditis in a neonate: A case report. J Saudi Heart Assoc 2012;24:195-9.
40. Jajoo M, Kumar V, Goyal VK, Garg A. Candida tropicalis infection in a term neonate with gall bladder masses and infective endocarditis. Asian Pac J Trop Med 2012;5:410-2.
41. Cetin M, Ozen S, Yildirimer M, Deveci M, Coskun S, Kizilkaya M. Premature newborn with intracardiac fungus balls and endocarditis which is curable only with antifungal therapy: case presentation. Clin Med Case Rep 2013;2:315-7.
42. Chaudhary N, Vishwanath M, Pahuja M, Borker A. Candida albicans endocarditis in a child with acute lymphoblastic leukemia: a dreaded complication of intensive chemotherapy. Indian J Med Paediatr Oncol 2013;34:28-30.
43. Ozdemir AA, Oral TK, Varol A. Fungal endocarditis in an extremely low birth weight infant: case report. Arch Argent Pediatr 2016;114:e117-20.
44. Oner T, Korun O, Celebi A. Rare presentation of Candida albicans: infective endocarditis and a pulmonary coin lesion. Cardiol Young 2018;28:602-4.
45. Babazadeh A, Ebrahimpour S, Taghi-Salehi-Omran M, Ahangar-Darabi Z, Karkhah A, Hamid-Abedi S, et al. Mitral-valve endocarditis due to Candida albicans: A case report. Acta Fac Med Naissensis 2018;35:345-50.
46. Vanhie ES, Bogers AJ, Helbing WA. Long-term outcome after tricuspid valvectomy in a neonate with Candida endocarditis: a case report. Cardiol Young 2019;29:528-30.
47. Portillo-Miño JD, Cerón-Muñoz E, Toro-Zapata C, Chaucanez-Bastidas Y. Endocarditis infecciosa debida a candida lusitaniae en un lactante menor: Reporte de caso. Infectio 2020;266-70
48. Prasad Gourav K, Mandal B, Mishra A, Narayanan Nayanar V. Successful medical management of fungal infective endocarditis post VSD closure. Ann Card Anaesth 2021;24:95-8.
49. Salehi S, Radvar M, Askari B. Candida albicans Endocarditis in a Child With Acute Lymphoblastic Leukemia: A Rare Case Report. Iran Heart J 2022;23:220-2.
50. Vassileva Z. Mitral valve replacement in a 3.9-kg infant with fungal endocarditis: A case report. Turk Gogus Kalp Damar Cerrahisi Derg 2022;30.
| Files | ||
| Issue | Vol 63 No 3 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/acta.v63i3.19714 | |
| Keywords | ||
| Candida endocarditis Pediatrics Children Neonate Risk factors Antifungal Resistance Biofilm | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rafie Khurgami M, Shirvani F, Yasin Z, Fattahi M, Tamimi P, Ghaderi A, Fattahi M. Management of Pediatric Candida Endocarditis: A Mini Review on Available Literature Between 2010-2022. Acta Med Iran. 2025;63(3):149-158.
