Short communicationIn vitro activities of amphotericin B and AmBisome against Aspergillus isolates recovered from Italian patients treated for haematological malignancies
Introduction
Invasive aspergillosis (IA) is a life-threatening fungal disease in immunocompromised patients, especially in those affected by haematological malignancies or undergoing haematopoietic stem cell transplantation. Amongst currently available antifungals for the treatment of systemic mycoses, the broad-spectrum polyene antifungal agent amphotericin B (AmB) has for many decades been considered the gold standard of antifungal treatment despite a high frequency of adverse effects such as infusional toxicity and nephrotoxicity associated with its use. Lipid-based formulations of AmB, ranging from lipid complexes to small unilamellar liposomes, are better tolerated than conventional AmB and are increasingly used for the treatment of IA [1]. Whilst voriconazole is now considered the gold standard for primary therapy of IA, liposomal amphotericin B (AmBisome®) is recommended in cases that are resistant or refractory to azole therapy [2] and it remains the drug of choice for empirical therapy in patients with febrile neutropenia.
Although antifungal resistance amongst Aspergillus spp. is uncommon, Aspergillus terreus is the first Aspergillus spp. to have shown reduced intrinsic susceptibility to AmB in vitro [3], whilst Aspergillus flavus and Aspergillus nidulans have been reported to be frequently less susceptible to AmB [4], [5], [6]. Furthermore, because of the potential of increasing minimum inhibitory concentrations (MICs) to AmB for less common species such as Neosartorya udagawae or Aspergillus lentulus, surveillance of Aspergillus susceptibility, especially amongst isolates causing IA, is desirable [7]. However, in vitro data regarding the antifungal activity of AmBisome against clinical isolates are rare [5], [6], despite a larger number of studies showing that lipid preparations of AmB are non-inferior to AmB in terms of in vivo efficacy [1].
The aim of this study was to investigate the in vitro activities of AmB and AmBisome against a large collection of Aspergillus spp. isolates from Italian patients with IA. In addition, for AmB the susceptibility test results obtained by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) method [8] were compared with those obtained by Etest.
Section snippets
Fungal isolates
A total of 103 Aspergillus spp. isolates were recovered from 102 patients with haematological malignancies who were diagnosed with proven or probable IA in the Department of Haematology of the Azienda Policlinico Umberto I (Rome, Italy) over a 9-year period (2001–2010). Isolates were obtained from the lower respiratory tract (n = 53), upper respiratory tract (n = 34), skin biopsies (n = 6), blood (n = 5) and central venous catheters (n = 5). All isolates were initially identified using morphological
Results and discussion
The 103 Aspergillus isolates studied were grouped in four species complexes (A. fumigatus, A. flavus, Aspergillus niger and A. terreus), with the majority of isolates being identified as A. oryzae (n = 38), A. fumigatus (n = 31), A. terreus (n = 13), A. flavus (n = 10) and A. niger (n = 5). The remaining isolates belonged to the species Neosartorya pseudofischeri (n = 1), N. udagawae (n = 1), Aspergillus tubingensis (n = 3) and Aspergillus foetidus (n = 1) (Table 1).
AmB MICs for quality control isolates were
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