Current Pediatric ReviewsCurrent Pediatric ReviewsCurrent Pediatric Reviews1573-39631875-6336Bentham Science64578610.2174/1573396320666230811092915MedicineResearch ArticleInvasive Fungal Infections in the Paediatric Intensive Care Unit: A Hong Kong StudyLiMarioinfo@benthamscience.netHonKaminfo@benthamscience.netYan LeungKareninfo@benthamscience.netHuiWuninfo@benthamscience.netLungDavidinfo@benthamscience.netHaShauinfo@benthamscience.netDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children’s HospitalDepartment of Paediatrics and Adolescent Medicine,, Hong Kong Children's HospitalDepartment of Paediatrics and Adolescent Medicine, Hong Kong Children's HospitalDepartment of Pathology, Queen Elizabeth Hospital/The Hong Kong Children’s Hospital,0104202420454054711012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1573-3963/article/view/645786

Introduction:Invasive fungal infections (IFI) cause significant mortality and morbidity in the Paediatric Intensive Care Unit (PICU). Early recognition and prompt treatment of invasive fungal infections are important. This article reviewed the mortality and morbidity of IFIs in the PICU of Hong Kong Children’s Hospital.

Methods:A retrospective review of all PICU admissions from April 2019 to May 2021 was per-formed. The following data were retrieved: age, gender, diagnosis, comorbidity, clinical manifestation, type of fungus, duration of stay at PICU, absolute neutrophil count, use of immunosuppressive therapy, presence of central venous catheter and use of total parental nutrition. The primary out-comes were the incidence and mortality of IFIs among PICU patients. The secondary outcomes were risk factors for developing IFI in PICU and clinical course of IFIs. Numerical variables were compared between groups by Mann-Whitney U test and categorical variables by Fisher’s exact test.

Results:There were 692 PICU admissions over the study period from April 2019 to May 2021. The crude mortality was 3% (n=24 death cases) in the PICU. Fourteen patients (2%) fulfilling the criteria for IFIs were identified using hospital electronic record system and according to PICU documentation. Eight of these 14 patients (57%) had hematological malignancy, 2 (17%) had solid tumours and 4 had non-oncological conditions. Eight (57%) patients were neutropenic with absolute neutrophil count less than 1x 109 at diagnosis of IFI. Ten (71%) had received immunosuppressive therapy including steroid, cyclosporin A, Mycophenolate mofetil (MMF), Sirolimus or tacrolimus. 12 (86%) had had central venous catheter. Eight (57%) were on parenteral nutrition. IFIs due to Rhizopus or Aspergillus infection (5/14), or in post-haematopoietic stem cell transplant patients (5/14) were as-sociated with non-survival (p = 0.031).

Conclusion:All patients with IFIs managed in the PICU had haemato-oncology diseases or were recipients of stem cell transplantation. IFIs with Rhizopus or Aspergillus as a group were associated with high mortality in the PICU. Awareness of this pathology with prompt diagnosis and treatment may improve the outcome of these infections and reduce the mortality.

Critical careinvasive fungal infectionstem cell transplantationhaemato-oncologic diseasesPICUmortality.Bongomin F, Gago S, Oladele R, Denning D. Global and multi-national prevalence of fungal diseases-estimate precision. J Fungi 2017; 3(4): 57. doi: 10.3390/jof3040057 PMID: 29371573Brissaud O, Guichoux J, Harambat J, Tandonnet O, Zaoutis T. Invasive fungal disease in PICU: Epidemiology and risk factors. Ann Intensive Care 2012; 2(1): 6. doi: 10.1186/2110-5820-2-6 PMID: 22356683Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis 2020; 71(6): 1367-76. doi: 10.1093/cid/ciz1008 PMID: 31802125Huang C, Xiao S, Cheng Y, et al. Clinical, laboratory, radiological, bronchoscopic, and outcome characteristics of pulmonary fungal infection in children in PICU in Central China: A case series. Front Pediatr 2022; 10: 822043. doi: 10.3389/fped.2022.822043 PMID: 35547541Ostrosky-Zeichner L, Al-Obaidi M. Invasive fungal infections in the intensive care unit. Infect Dis Clin North Am 2017; 31(3): 475-87. doi: 10.1016/j.idc.2017.05.005 PMID: 28687215Ramos JT, Francisco L, Daoud Z. Invasive fungal infections in children: Similarities and differences with adults. Rev Esp Quimioter 2016; 29 (Suppl. 1): 59-65. PMID: 27608317Ashley ED, Drew R, Johnson M, et al. Cost of invasive fungal infections in the era of new diagnostics and expanded treatment options. Pharmacotherapy 2012; 32(10): 890-901. doi: 10.1002/j.1875-9114.2012.01124 PMID: 23033228Ananda-Rajah MR, Cheng A, Morrissey CO, et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother 2011; 55(5): 1953-60. doi: 10.1128/AAC.01423-10 PMID: 21357302Maschmeyer G, Patterson TF. New immunosuppressive agents and risk for invasive fungal infections. Curr Infect Dis Rep 2009; 11(6): 435-8. doi: 10.1007/s11908-009-0063-x PMID: 19857382Arning M, Aul C. Prophylaxis against mycoses in neutropenic patients. Mycoses 1994; 37 (Suppl. 2): 70-6. PMID: 7541892Ibáñez-Martínez E, Ruiz-Gaitán A, Pemán-García J. Update on the diagnosis of invasive fungal infection. Rev Esp Quimioter 2017; 30 (Suppl. 1): 16-21. PMID: 28882009Sipsas NV, Kontoyiannis DP. Invasive fungal infections in patients with cancer in the intensive care unit. Int J Antimicrob Agents 2012; 39(6): 464-71. doi: 10.1016/j.ijantimicag.2011.11.017 PMID: 22337064Pathakumari B, Liang G, Liu W. Immune defence to invasive fungal infections: A comprehensive review. Biomed Pharmacother 2020; 130: 110550. doi: 10.1016/j.biopha.2020.110550 PMID: 32739740Mei-Sheng Riley M. Invasive fungal infections among immunocompromised patients in critical care settings. Crit Care Nurs Clin North Am 2021; 33(4): 395-405. doi: 10.1016/j.cnc.2021.07.002 PMID: 34742496Corredor Andrés B, Muñoz Calvo MT, López Pino MÁ, et al. Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences. Anales de Pediatría (English Edition) 2019; 90(5): 293-300. doi: 10.1016/j.anpede.2018.05.005 PMID: 29895434von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, Kurzai O. Invasive Fungal Infection. Dtsch Arztebl Int 2019; 116(16): 271-8. PMID: 31159914Ahmadi A, Ardehali SH, Beigmohammadi MT, et al. Invasive candidiasis in intensive care unit; consensus statement from an Iranian panel of experts, July 2013. JRSM Open 2014; 5(3) doi: 10.1177/2042533313517689 PMID: 25057376José P, Alvarez-Lerma F, Maseda E, et al. Invasive fungal infection in crtically ill patients: Hurdles and next challenges. J Chemother 2019; 31(2): 64-73. doi: 10.1080/1120009X.2018.1557799 PMID: 30761948Pappas PG, Lionakis MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers 2018; 4(1): 18026. doi: 10.1038/nrdp.2018.26 PMID: 29749387Dagenais TRT, Keller NP. Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev 2009; 22(3): 447-65. doi: 10.1128/CMR.00055-08 PMID: 19597008Park SK, Jung H, Kang MS. Localized bilateral paranasal mucormycosis: A case in an immunocompetent patient. Acta Otolaryngol 2006; 126(12): 1339-41. doi: 10.1080/00016480500316852 PMID: 17101598Tortorano AM, Dho G, Prigitano A, et al. Invasive fungal infections in the intensive care unit: A multicentre, prospective, observational study in Italy (2006-2008). Mycoses 2012; 55(1): 73-9. doi: 10.1111/j.1439-0507.2011.02044.x PMID: 21668521Haidar G, Singh N. How we approach combination antifungal therapy for invasive aspergillosis and mucormycosis in transplant recipi-ents. Transplantation 2018; 102(11): 1815-23. doi: 10.1097/TP.0000000000002353 PMID: 29975240Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005; 18(3): 556-69. doi: 10.1128/CMR.18.3.556-569.2005 PMID: 16020690Loubet D, Sarton B, Lelièvre L, et al. Fatal mucormycosis and aspergillosis coinfection associated with haemophagocytic lymphohistio-cytosis: A case report and literature review. J Mycol Med 2023; 33(1): 101325. doi: 10.1016/j.mycmed.2022.101325 PMID: 36270214Deboni MCZ, Pozzani VR, Lisboa T, Hiraki K, Viplich R, Naclério-Homem MG. Mucormycosis in an immunocompetent patient: Follow-up of 1 year after treatment. Acta Otolaryngol 2006; 126(9): 993-6. doi: 10.1080/00016480500534439 PMID: 16864500Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54 (Suppl. 1): 16-22. doi: 10.1093/cid/cir865Cai XF, Sun JM, Dong ZQ, Li WB. Invasive fungal infections in the pediatric intensive care unit: A clinical analysis of 38 cases. Zhongguo Dang Dai Er Ke Za Zhi 2013; 15(8): 644-8. PMID: 23965877Leung KKY, Ray S, Chan GCF, Hon KL. Functional outcomes at PICU discharge in hemato-oncology children at a tertiary oncology center in Hong Kong. Int J Clin Oncol 2022; 27(12): 1904-15. doi: 10.1007/s10147-022-02244-3 PMID: 36149516Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother 2017; 72 (Suppl. 1): i39-47. doi: 10.1093/jac/dkx032 PMID: 28355466Bodro M, Sabé N, Gomila A, et al. Risk factors, clinical characteristics, and outcomes of invasive fungal infections in solid organ transplant recipients. Transplant Proc 2012; 44(9): 2682-5. doi: 10.1016/j.transproceed.2012.09.059 PMID: 23146493Chermetz M, Gobbo M, Rupel K, et al. Combined orofacial aspergillosis and mucormycosis: Fatal complication of a recurrent paediatric glioma-case report and review of literature. Mycopathologia 2016; 181(9-10): 723-33. doi: 10.1007/s11046-016-0021-8 PMID: 27350324Sadeghi G, Ebrahimi-Rad M, Mousavi SF, Shams-Ghahfarokhi M, Razzaghi-Abyaneh M. Emergence of non- Candida albicans species: Epidemiology, phylogeny and fluconazole susceptibility profile. J Mycol Med 2018; 28(1): 51-8. doi: 10.1016/j.mycmed.2017.12.008 PMID: 29366545Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel) 2019; 5(1): 26. doi: 10.3390/jof5010026 PMID: 30901907Vidovic A, Arsic-Arsenijevic V, Tomin D, et al. Proven invasive pulmonary mucormycosis successfully treated with amphotericin B and surgery in patient with acute myeloblastic leukemia: A case report. J Med Case Reports 2013; 7(1): 263. doi: 10.1186/1752-1947-7-263 PMID: 24299522Cadena J, Thompson GR III, Patterson TF. Invasive aspergillosis. Infect Dis Clin North Am 2016; 30(1): 125-42. doi: 10.1016/j.idc.2015.10.015 PMID: 26897064Cornely OA, Aversa F, Cook P, et al. Evaluating the role of prophylaxis in the management of invasive fungal infections in patients with hematologic malignancy. Eur J Haematol 2011; 87(4): 289-301. doi: 10.1111/j.1600-0609.2011.01682.x PMID: 21752098Zeng H, Wu Z, Yu B, et al. Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies. BMC Cancer 2021; 21(1): 404. doi: 10.1186/s12885-021-07973-8 PMID: 33853560Le Clech L, Uguen M, Quinio D, et al. Evaluation of posaconazole antifungal prophylaxis in reducing the incidence of invasive aspergillo-sis in patients with acute myeloid leukemia. Curr Res Transl Med 2020; 68(1): 23-8. doi: 10.1016/j.retram.2019.11.002 PMID: 31787568Kanda Y. Invasive fungal infection management in patients with hematological malignancies. Rinsho Ketsueki 2022; 63(9): 1270-8. PMID: 36198553Mellinghoff SC, Panse J, Alakel N, et al. Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Ann Hematol 2018; 97(2): 197-207. doi: 10.1007/s00277-017-3196-2 PMID: 29218389Blyth CC, Hale K, Palasanthiran P, O’Brien T, Bennett MH. Antifungal therapy in infants and children with proven, probable or suspected invasive fungal infections. Cochrane Libr 2010; (2): CD006343. doi: 10.1002/14651858.CD006343.pub2 PMID: 20166083