Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study

Francelise Bridi Cavassin; Marcello Mihailenko Chaves Magri; Jose Ernesto Vidal; Fabianne Altruda de Moraes Costa Carlesse; Diego Rodrigues Falci; João Luís Baú-Carneiro; Giovanni Luís Breda; Fábio de Araújo Motta; Cássia Silva de Miranda Godoy; Renata de Bastos Ascenço Soares; Carla Sakuma De Oliveira; Ana Verena Almeida Mendes; Hugo Paz Morales; Patrícia Silva Montes; Mariane Taborda; Caroline Martins Rego; Maíra Araujo Félix; Paula Pacheco Katopodis; Julia Raquel da Silva do Ó; Mirela Pereira Lima Abrão; Talita Teles Teixeira Pereira; Flávio Queiroz-Telles

doi:10.1016/j.clinthera.2024.01.011

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study

Clin Ther. 2024 Feb 24:S0149-2918(24)00019-5. doi: 10.1016/j.clinthera.2024.01.011. Online ahead of print.

Authors

Francelise Bridi Cavassin¹, Marcello Mihailenko Chaves Magri², Jose Ernesto Vidal³, Fabianne Altruda de Moraes Costa Carlesse⁴, Diego Rodrigues Falci⁵, João Luís Baú-Carneiro⁶, Giovanni Luís Breda⁷, Fábio de Araújo Motta⁸, Cássia Silva de Miranda Godoy⁹, Renata de Bastos Ascenço Soares¹⁰, Carla Sakuma De Oliveira¹¹, Ana Verena Almeida Mendes¹², Hugo Paz Morales¹³, Patrícia Silva Montes², Mariane Taborda², Caroline Martins Rego³, Maíra Araujo Félix³, Paula Pacheco Katopodis¹⁴, Julia Raquel da Silva do Ó¹⁴, Mirela Pereira Lima Abrão¹⁵, Talita Teles Teixeira Pereira¹², Flávio Queiroz-Telles¹⁶

Affiliations

¹ Universidade Federal do Paraná (UFPR), Curitiba, Brazil. Electronic address: francelise.cavassin@ufpr.br.
² Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC/FAMUSP), São Paulo, Brazil.
³ Instituto de Infectologia Emílio Ribas (IIER), São Paulo, Brazil.
⁴ Universidade Federal de São Paulo/ Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, Brazil.
⁵ Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
⁶ Faculdades Pequeno Príncipe (FPP), Curitiba, Brazil.
⁷ Hospital de Clínicas da Universidade Federal do Paraná (HC/UFPR), Curitiba, Brazil.
⁸ Hospital Pequeno Príncipe (HPP), Curitiba, Brazil.
⁹ Hospital de Doenças Tropicais Dr. Anuar Auad (HDT), Goiânia, Brazil.
¹⁰ Hospital Estadual de Doenças Tropicais Dr. Anuar Auad (HDT), Goiânia, Brazil.
¹¹ Hospital Universitário do Oeste do Paraná (HUOP), Cascavel, Brazil.
¹² Hospital São Rafael (HSR), Salvador, Brazil.
¹³ Hospital Erasto Gaertner (HEG), Curitiba, Brazil.
¹⁴ Pontifícia Universidade Católica de Goiás, Goiânia, Brazil.
¹⁵ Universidade Federal de Goiás, Goiânia, Brazil.
¹⁶ Universidade Federal do Paraná (UFPR), Hospital de Clínicas da Universidade Federal do Paraná (HC/UFPR), Curitiba, Brazil.

PMID: 38403508
DOI: 10.1016/j.clinthera.2024.01.011

Abstract

Purpose: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC.

Methods: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety.

Findings: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%.

Implications: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Keywords: Amphotericin B; Antifungals agents; Brazil; Safety; Treatment outcome.