title: Amphotericin B in vitro resistance is associated with fatal Aspergillus flavus infection.
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.
authors.affiliation: Laboratoire de Biologie Moléculaire Parasitaire et Fongique, Faculté de Médecine, Sfax, Tunisia.
authors.forename: Inès
authors.initials: I
authors.lastname: Hadrich
authors.forename: Fattouma
authors.initials: F
authors.lastname: Makni
authors.forename: Sourour
authors.initials: S
authors.lastname: Neji
authors.forename: Fatma
authors.initials: F
authors.lastname: Cheikhrouhou
authors.forename: Hatem
authors.initials: H
authors.lastname: Bellaaj
authors.forename: Moez
authors.initials: M
authors.lastname: Elloumi
authors.forename: Ali
authors.initials: A
authors.lastname: Ayadi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ranque
mesh_terms: D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001231:Aspergillus flavus / Q000187:drug effects* / Q000302:isolation & purification; D015331:Cohort Studies; D025141:Drug Resistance, Fungal; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B