Evaluation of the efficacy, safety and economy of different amphotericin B formulations in invasive fungal disease: A retrospective cohort study

Abstract

Background: Fungal infections have emerged as an increasingly serious public health challenge globally. Four Formulations of amphotericin B are widely used in antifungal therapy. Despite the same active ingredient, they probably differ in efficacy, safety and economics.

Aim: This study aimed to explore the differences in efficacy, safety and economy among different formulations of amphotericin B in patients with IFD.

Methods: We conducted a retrospective study at a tertiary hospital, examining patients who were administered amphotericin B from June 2023 to March 2025, to assess the efficacy, safety and economy of different amphotericin B Formulations in invasive fungal disease.

Results: (1) A total of 71 patients were included. Patients with potential renal injury are more likely to choose liposomal amphotericin B (p = 0.021). (2) Liposomal amphotericin has the accelerated therapeutic onset (p = 0.042), amphotericin B deoxycholate has the delayed therapeutic effect (p = 0.031), the effective response of liposomal amphotericin B in elders was significantly lower (p = 0.022), and the counterpart of amphotericin B deoxycholate in females was significantly higher (p = 0.01). (3) The main adverse events of the three amphotericin B formulations were kidney injury (p < 0.001), there was no significant inter-group difference. (4) The amphotericin B deoxycholate group incurred the most economical total cost (p < 0.01), daily cost (p < 0.01) and cost-effectiveness.

Conclusion: Amphotericin B formulations exhibit marked variations in efficacy and economy profiles, necessitating individualized selection guided by specific clinical characteristics. Rigorous monitoring of renal function remains imperative throughout the therapeutic course.

Keywords

Amphotericin B / Retrospective cohort study / Invasive fungal disease / Formulations / Nephrotoxicity

Declarations

Not applicable.

Authors' contributions

Shizhao Yuan: Writing - review & editing, Writing - original draft, Visualization, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Yan Liu: Supervision, Resources, Project administration, Funding acquisition. Shuoxian Jia: Supervision, Resources, Project administration, Funding acquisition. Yan Zhao: Project administration, Methodology, Investigation. Ziyi Wang: Project administration, Methodology, Investigation. Jing yu: Supervision, Resources, Project administration, Funding acquisition. Chunhua Zhou: Supervision, Resources, Project administration, Funding acquisition. Shuai Liu: Writing - review & editing, Writing - original draft, Visualization, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

Ethics approval and consent to participate

This retrospective study was approved by the Ethics Committee of the First Hospital of Hebei Medical University (No.20220447).

Consent for publication

All authors have read and approved the final manuscript, and consent to its publication.

Data availability

Detailed information can be provided by the corresponding author upon reasonable request.

Funding

This work was supported by the S&T Program of Hebei [No. H2022206548].

Declaration of Competing Interest

The authors confirm that the funding had no infuence on the study results. There are no conficts of interest associated with this publication.

Acknowledgments

Not Applicable.

Authors' other information

Not Applicable.

References

[1] Denning DW. Global incidence and mortality of severe fungal disease. Lancet Infect Dis. 2024; 24:e428-e438.

[2] Oa C, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the european confederation of medical mycology in cooperation with the mycoses study group education and research consortium. Lancet Infect Dis. 2019;19.

[3] Pappas PG, 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.

[4] Cavassin FB, Baú-Carneiro JL, Vilas-Boas RR, Queiroz-Telles F. Sixty years of amphotericin B: an overview of the main antifungal agent used to treat invasive fungal infections. Infect Dis Ther. 2021; 10:115-147.

[5] Medical Mycology Society of Chinese Medicine and Education Association. Multidisciplinary expert consensus on the clinical rational application of different formulations of amphotericin B (2024 edition). Chinese Journal of Internal Medicine 63, 230-257 (2024).

[6] Bekersky I, et al. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin b (AmBisome) and amphotericin b deoxycholate in humans. Antimicrob Agents Chemother. 2002; 46:828-833.

[7] Groll AH, et al. Comparative efficacy and distribution of lipid formulations of amphotericin b in experimental candida albicans infection of the central nervous system. J Infect Dis. 2000; 182:274-282.

[8] Jadhav MP, et al. A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin b (Fungisome) versus conventional amphotericin b in the empirical treatment of febrile neutropenia in India. Indian J Cancer. 2012; 49:107-113.

[9] 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.

[10] Nokura Y, et al. Comparison of adverse event profiles of amphotericin b formulations using Real-World data. Cureus. 2024; 16:e71588.

[11] Donnelly JP, 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.

[12] Qin J, et al. Real-World effectiveness and safety of isavuconazole versus amphotericin b for patients with invasive mucormycosis. Microorganisms. 2025; 13:55.

[13] Boogaerts M, et al. Intravenous and oral itraconazole versus intravenous amphotericin b deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving Broad-Spectrum antibacterial therapy: a randomized, controlled trial. Ann Intern Med. 2001; 135:412-422.

[14] Lopez-Berestein G, et al. Treatment of systemic fungal infections with liposomal amphotericin b. Arch Intern Med. 1989; 149:2533-2536.

[15] Yigeng Cao, et al. Safety and efficacy of amphotericin b colloidal dispersion in the salvage treatment of invasive fungal disease. Chin J Infect Chemother. 2023; 23:443-448.

[16] Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. JoF. 2019; 5:26.

[17] Özbek L, et al. COVID-19-associated mucormycosis: a systematic review and meta-analysis of 958 cases. Clin Microbiol Infect. 2023; 29:722-731.

[18] Mesa-Arango AC, Scorzoni L. & zaragoza O. It only takes one to do many jobs: amphotericin b as antifungal and immunomodulatory drug. Front Micro. 2012;3.

[19] von Lilienfeld-Toal M, Wagener J, Einsele H, Cornely OA, Kurzai O. Invasive fungal infection. Dtsch Arztebl Int. 2019; 116:271-278.

[20] Lass-Flörl C, Steixner S. The changing epidemiology of fungal infections. Mol Asp Med. 2023; 94:101215.

[21] Cavassin FB, et al. Effectiveness, tolerability, and safety of different amphotericin b formulations in invasive fungal infections: a multicenter, retrospective, observational study. Clin Ther. 2024; 46:322-337.

[22] Jadhav M, et al. A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin b (Fungisome™) versus conventional amphotericin b in the empirical treatment of febrile neutropenia in India. Indian J Cancer. 2012; 49:107.

[23] Umemura K, et al. Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin b and amphotericin b deoxycholate for antifungal prophylaxis after lung transplantation. J Infect Chemother. 2024; 30:741-745.

[24] Tonin FS, et al. Efficacy and safety of amphotericin b formulations: a network meta-analysis and a multicriteria decision analysis. J Pharm Pharmacol. 2017; 69:1672-1683.

[25] Tan Y, et al. Safety of different amphotericin b formulations among AIDS patients with invasive fungal disease: a retrospective observational study. AIDS Res Ther. 2024; 21:66.

[26] 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.

[27] Bekersky I, et al. Plasma protein binding of amphotericin b and pharmacokinetics of bound versus unbound amphotericin b after administration of intravenous liposomal amphotericin b (AmBisome) and amphotericin b deoxycholate. Antimicrob Agents Chemother. 2002; 46:834-840.

[28] Faustino C, Pinheiro L. Lipid systems for the delivery of amphotericin b in antifungal therapy. Pharmaceutics. 2020; 12:29.

[29] Botero Aguirre JP, Restrepo Hamid AM. Amphotericin b deoxycholate versus liposomal amphotericin B: effects on kidney function. Cochrane Database Syst Rev. 2015;2015:CD010481.

[30] Lobo Borba HH, et al. Cost-effectiveness of amphotericin b formulations in the treatment of systemic fungal infections. Mycoses. 2018; 61:754-763.