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

J Antimicrob Chemother. 2024 Oct 1;79(10):2598-2606. doi: 10.1093/jac/dkae264.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Amphotericin B* / adverse effects
  • Amphotericin B* / therapeutic use
  • Antifungal Agents* / adverse effects
  • Antifungal Agents* / therapeutic use
  • Brazil / epidemiology
  • Deoxycholic Acid / adverse effects
  • Deoxycholic Acid / therapeutic use
  • Drug Combinations
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / mortality
  • Histoplasmosis* / drug therapy
  • Histoplasmosis* / mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypokalemia / chemically induced
  • Hypokalemia / mortality
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Amphotericin B
  • Antifungal Agents
  • liposomal amphotericin B
  • amphotericin B, deoxycholate drug combination
  • Deoxycholic Acid
  • Drug Combinations