Amphotericin B in vitro resistance is associated with fatal Aspergillus flavus infection

Med Mycol. 2012 Nov;50(8):829-34. doi: 10.3109/13693786.2012.684154. Epub 2012 May 15.

Abstract

Whether in vitro antifungal susceptibility findings correlate with the outcome of patients with invasive aspergillosis (IA) remains debated. This study aimed to test whether IA patients' outcomes were associated with in vitro susceptibility results. To do so, we determined the in vitro susceptibility to amphotericin B (AMB) of 37 Aspergillus flavus isolates from 14 patients with haematological malignancies diagnosed with proven or probable IA, of which 13 were treated with AMB deoxycholate. Minimal inhibitory concentrations (MICs) were determined by Etest with the isolates classified as in vitro sensitive (AMB-S) or resistant (AMB-R) if their MICs were < 2 or ≥ 2 mg/l, respectively. The association of the patients' death with primary disease, administered antifungal treatment, and infection with AMB-R A. flavus was tested using generalized estimating equations logistic regression. We assessed AMB-R in 31/37 (84%) isolates. In the patients treated with AMB, the survival rate was 2/3 (67%) and 2/9 (22%) for those infected with AMB-S or AMB-R A. flavus, respectively. Both infection with AMB-R A. flavus (P = 0.014) strain and acute myelocytic leukaemia as the underlying primary disease (P = 0.036) were independent predictors of death. Our findings indicate that in vitro resistance predicts a poor outcome in patients with A. flavus invasive disease treated with AMB. Recent advances in non-culture-based microbiological methods should not discourage efforts to obtain in vitro antifungal susceptibility results, which are critical for the choice of antifungal therapy in patients with IA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amphotericin B / pharmacology*
  • Amphotericin B / therapeutic use
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Aspergillus flavus / drug effects*
  • Aspergillus flavus / isolation & purification
  • Cohort Studies
  • Drug Resistance, Fungal*
  • Female
  • Hematologic Neoplasms / complications
  • Humans
  • Invasive Pulmonary Aspergillosis / drug therapy
  • Invasive Pulmonary Aspergillosis / microbiology*
  • Invasive Pulmonary Aspergillosis / mortality*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Antifungal Agents
  • Amphotericin B