ORIGINAL PAPER
Results of liposomal amphotericin B treatment in pediatric invasive fungal infections: a single-center experience
 
More details
Hide details
1
Department of Pediatric Oncology and Hematology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
 
2
Department of Paediatric Oncology and Hematology, University Children’s Hospital, Krakow, Poland
 
3
Department of Infectious Diseases and Hepatology, Medical University of Silesia in Katowice, Poland
 
4
Student Scientific Group of Pediatric Oncology and Hematology, Jagiellonian University Medical College, Krakow, Poland
 
 
Submission date: 2025-04-09
 
 
Final revision date: 2025-06-11
 
 
Acceptance date: 2025-07-07
 
 
Publication date: 2025-09-24
 
 
Corresponding author
Szymon Skoczeń
Szymon Skoczeń, Klinika Onkologii i Hematologii Dziecięcej, Uniwersytet Jagielloński Collegium Medicum, 24 Gołębia St., 31-007 Krakow, Poland
 
 
Pediatr Pol 2025;61(3):216-222
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Invasive fungal infections (IFIs) are a common problem, and a major cause of morbidity and mortality in immunocompromised children. Most of them have at least one IFI during long and intensive treatment administered in oncology and hematology departments. Due to limited diagnostic options, final diagnosis of IFIs is often difficult and time-consuming, therefore empirical or prophylactic antifungal treatment is frequently initiated to avoid delays in therapy. The limited overall outcome led to the strategy of initiat­ing either empirical or pre-emptive antifungal therapy before final diagnosis. One of the most effective antifungal drugs is liposomal amphotericin B (LAmB). The aim of the study was to retrospectively analyze patients treated using LAmB at the Department of Pediatric Oncology and Hematology UCH between 2015 and 2022.

Material and methods:
Study group included 59 patients, aged 2–18 years (53% boys, 47% girls). Half of children were diagnosed with acute leukemia (acute lymphoblastic leukemia: 33%, acute myeloid leukemia: 17%), while the other half suffered from different cancers and immune disorders, such as Burkitt’s lymphoma, T-cell non-Hodgkin lymphoma, Ewing’s sarcoma, osteosarcoma, synovial sarcoma, neuroblastoma, central nervous system tumors, aplastic anemia, hemophagocytic histiocytosis, severe combined immunodeficiency, and gona­doblastoma. Data concerning patients status, therapy, and follow-up, including primary disease, chemo/radiotherapy, immune status, neutropenia duration, indications for antifungal therapy, response to therapy, supportive treatment, and complications, were analyzed.

Results:
Eighty percent of patients received LAmB as empirical treatment. In 46% of patients, LAmB was applied as monotherapy, while in combination, micafungin, fluconazole, or voriconazole were used. Almost all patients presented an altered immune status due to pancytopenia and hypogammaglobulinemia. The median time of neutropenia before fungal infection was 19 days. Complications observed during LAmB therapy included liver and/or kidney dysfunctions and important electrolytes alteration. However, 76% of patients responded to the treatment.

Conclusions:
The results indicated that adverse events were not linked to the cumulative dose of LAmB. There were no significant differences in cumulative doses between patients who experienced adverse events and those who did not. Kidney-related adverse events were weakly associated with fatal outcomes.
REFERENCES (23)
1.
Donnelly 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: 1367-1376.
 
2.
Groll AH, Rijnders BJA, Walsh TJ, et al. Clinical pharmacokinetics, pharmacodynamics, safety and efficacy of liposomal amphotericin B. Clin Infect Dis 2019; 68 (Suppl 4): S260-S274. DOI: 10.1093/cid/ciz076.
 
3.
Lestner JM, Groll AH, Aljayyoussi G, et al. Population pharmacokinetics of liposomal amphotericin B in immunocompromised children. Antimicrob Agents Chemother 2016; 60: 7340-7346.
 
4.
Tollemar J, Klingspor L, Ringdén O. Liposomal amphotericin B (AmBisome) for fungal infections in immunocompromised adults and children. Clin Microbiol Infect 2001; 7 Suppl 2: 68-79. DOI: 10.1111/j.1469-0691.2001.tb00012.x.
 
5.
Botero Aguirre JP, Restrepo Hamid AM. Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function. Cochrane Database Syst Rev 2015; 11: CD010481. DOI: 10.1002/ 14651858.CD010481.pub2.
 
6.
Mendoza-Palomar N, Soques E, Benitez-Carabante MI, et al. Low-dose liposomal amphotericin B for antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell transplantation. J Antimicrob Chemother 2020; 75: 2264-2271.
 
7.
Yoshida M, Tamura K, Masaoka T, Nakajo E. A real-world prospective observational study on the efficacy and safety of liposomal amphotericin B in 426 patients with persistent neutropenia and fever. J Infect Chemother 2021; 27: 277-283.
 
8.
Yamashita C, Takesue Y, Matsumoto K, et al. Echinocandins versus non-echinocandins for empirical antifungal therapy in patients with hematological disease with febrile neutropenia: a systematic review and meta-analysis. J Infect Chemother 2020; 26: 596-603.
 
9.
Astellas Pharma Sp. z o.o. Charakterystyka Produktu Leczniczego: Ambisome (Amfoterycyna B w postaci liposomalnej). 2024. Accessed at: http://chpl.com.pl/data_files/....
 
10.
Walsh TJ, Lewis RE, Adler-Moore J. Pharmacology of liposomal amphotericin B: an introduction to preclinical and clinical advances for treatment of life-threatening invasive fungal infections. Clin Infect Dis 2019; 68 (Suppl 4): S241-S243. DOI: 10.1093/cid/ciz091.
 
11.
U.S. Food and Drug Administration. AmBisome (Amphotericin B) Liposome for Injection. 2012. Accessed at: https://www.accessdata.fda.gov....
 
12.
Xess I, Pagano L, Dabas Y. Invasive fungal infections 2021. J Fungi (Basel) 2022; 8: 760. DOI: 10.3390/jof8080760.
 
13.
Fang W, Wu J, Cheng M, et al. Diagnosis of invasive fungal infections: challenges and recent developments. J Biomed Sci 2023; 30: 42. DOI: https://doi.org/10.1186/s12929....
 
14.
Bassetti M, Azoulay E, Kullberg BJ, et al. EORTC/MSGERC definitions of invasive fungal diseases: summary of activities of the Intensive Care Unit Working Group. Clin Infect Dis 2021; 72 (Suppl 2): S121-S127. DOI: https://doi.org/10.1093/cid/ci....
 
15.
Belinschi V, Iheagwara C, Muhanna A. Once-weekly liposomal amphotericin B use for maintenance and consolidation phase treatment of cryptococcal meningitis in patients with AIDS. Cureus 2024; 16: e55824. DOI: 10.7759/cureus.55824.
 
16.
Stott KE, Beardsley J, Whalley S, et al. Population pharmacokinetic model and meta-analysis of outcomes of amphotericin B deoxycholate use in adults with cryptococcal meningitis. Antimicrob Agents Chemother 2018; 62: e02526-17. DOI: 10.1128/AAC.02526-17. Erratum in: Antimicrob Agents Chemother 2018; 62: e02249-18. DOI: 10.1128/AAC.02249-18.
 
17.
Stone NR, Bicanic T, Salim R, Hope W. Liposomal amphotericin B (AmBisome(®)): a review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs 2016; 76: 485-500.
 
18.
Sunakawa K, Tsukimoto I, Tsunematsu Y, et al. Evaluation of the safety and efficacy of liposomal amphotericin B (L-AMB) in children. J Infect Chemother 2012; 18: 456-465.
 
19.
Fisher MA, Talbot GH, Maislin G, et al. Risk factors for amphotericin B-associated nephrotoxicity. Am J Med 1989; 87: 547-552.
 
20.
Falci DR, da Rosa FB, Pasqualotto AC. Comparison of nephroto­xicity associated to different lipid formulations of amphotericin B: a real-life study. Mycoses 2015; 58: 104-112.
 
21.
Personett HA, Kayhart BM, Barreto EF, et al. Renal recovery following liposomal amphotericin B-induced nephrotoxicity. Int J Nephrol 2019; 2019: 8629891. DOI: 10.1155/2019/8629891.
 
22.
Girmenia C, Cimino G, Micozzi A, et al. Risk factors for nephrotoxicity associated with conventional amphotericin B therapy. Am J Med 2002; 113: 351. DOI: 10.1016/s0002-9343(02)01140-3.
 
23.
Folk A, Balta C, Herman H, et al. Flucytosine and amphotericin B coadministration induces dose-related renal injury. Dose Response 2017; 15: 1559325817703461. DOI: 10.1177/1559325817703461.
 
Journals System - logo
Scroll to top