A multicentre study of amphotericin B treatment for histoplasmosis: assessing mortality rates and adverse events

Author:

Sekiguchi William Kazunori1,Oliveira Vítor Falcão de1ORCID,Cavassin Francelise Bridi2,Taborda Mariane1,Kono Magri Adriana Satie Gonçalves1,Cruz Isabela Carvalho Leme Vieira da1,Vidal Jose Ernesto13,Falci Diego Rodrigues4,de Miranda Godoy Cássia Silva5,Soares Renata de Bastos Ascenço5,de Oliveira Carla Sakuma6,Mendes Ana Verena Almeida7,Breda Giovanni Luís8,Rego Caroline Martins3,Félix Maíra Araujo3,Katopodis Paula Pacheco9,da Silva do Ó Julia Raquel9,Abrão Mirela Pereira Lima10,Baú-Carneiro João Luiz11,Pereira Talita Teles Teixeira7,Queiroz-Telles Flávio812,Chaves Magri Marcello Mihailenko1

Affiliation:

1. Infectious and Parasitic Diseases Division, Faculdade de Medicina, Hospital das Clínicas (HCFMUSP), Universidade de São Paulo , São Paulo, SP , Brazil

2. Internal Medicine and Health Sciences Department, Universidade Federal do Paraná (UFPR) , Curitiba, PR , Brazil

3. Infectious Diseases Department, Instituto de Infectologia Emílio Ribas (IIER) , São Paulo, SP , Brazil

4. Infectious Diseases Department, Hospital de Clínicas de Porto Alegre (HCPA) , Porto Alegre, RS , Brazil

5. Medical Education and Research Department, Hospital de Doenças Tropicais Dr. Anuar Auad (HDT) , Goiânia, GO , Brazil

6. Infectious Diseases Department, Hospital Universitário do Oeste do Paraná (HUOP) , Cascavel, PR , Brazil

7. Infectious Diseases Department, Hospital São Rafael (HSR) , Salvador, BA , Brazil

8. Infectious Diseases Department, Hospital de Clínicas da Universidade Federal do Paraná (HC/UFPR) , Curitiba, PR , Brazil

9. Medical Education and Research Department, Pontifícia Universidade Católica de Goiás , Goiânia, GO , Brazil

10. Medical Education and Research Department, Universidade Federal de Goiás , Goiânia, GO , Brazil

11. Faculdades Pequeno Príncipe (FPP), Medical School , Curitiba, PR , Brazil

12. Public Health Department, Universidade Federal do Paraná (UFPR) , Curitiba, PR , Brazil

Abstract

Abstract Background Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. Objectives Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. Methods This multicentre retrospective cohort study (January 2014–December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. Results The study included 215 patients, mostly male (n = 158, 73%) with HIV infection (n = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n = 19, 90%), acute kidney injury (n = 96, 59%), hypokalaemia (n = 73, 55%) and infusion reactions (n = 44, 20%) during treatment. Conclusions We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis.

Publisher

Oxford University Press (OUP)

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