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Amphotericin B in vitro resistance is associated with fatal Aspergillus flavus infection
Inès Hadrich1, Fattouma Makni, Sourour Neji
1Laboratoire de Biologie Moléculaire Parasitaire et Fongique, Faculté de Médecine, Sfax, Tunisia.
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.
Insights
Invasive aspergillosis patients infected with amphotericin B-resistant Aspergillus flavus showed poorer outcomes. Antifungal susceptibility testing is crucial for guiding invasive aspergillosis treatment decisions.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Clinical Microbiology
Background:
- The correlation between in vitro antifungal susceptibility and patient outcomes in invasive aspergillosis (IA) is not fully established.
- Aspergillus flavus is a significant cause of IA, particularly in immunocompromised patients.
Purpose of the Study:
- To investigate the association between in vitro antifungal susceptibility of Aspergillus flavus and patient outcomes in invasive aspergillosis.
- To determine if amphotericin B resistance in A. flavus predicts treatment failure or mortality.
Main Methods:
- Determined in vitro susceptibility of 37 A. flavus isolates from 14 patients with hematological malignancies to amphotericin B using Etest.
- Classified isolates as susceptible (MIC < 2 mg/l) or resistant (MIC ≥ 2 mg/l).
- Analyzed patient survival rates in relation to A. flavus susceptibility, primary disease, and antifungal treatment using logistic regression.
Main Results:
- A high prevalence of amphotericin B resistance (84%) was observed in the A. flavus isolates.
- Patients infected with amphotericin B-resistant A. flavus had significantly lower survival rates (22%) compared to those with susceptible isolates (67%) when treated with amphotericin B.
- Infection with amphotericin B-resistant A. flavus and acute myelocytic leukemia were independent predictors of death.
Conclusions:
- In vitro resistance of Aspergillus flavus to amphotericin B is a significant predictor of poor outcomes in patients with invasive aspergillosis treated with this agent.
- Antifungal susceptibility testing remains critical for selecting appropriate therapy and improving patient outcomes in invasive aspergillosis.
- Despite advances in non-culture-based methods, in vitro susceptibility data are essential for clinical decision-making.
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