Abstract
The resistance of Aspergillus species to antifungal is increasingly reported and the knowledge of the local epidemiology and antifungal susceptibility pattern is pivotal to define adequate treatment policies. Our study aimed to: 1) describe the in vitro antifungal susceptibility profile of the Aspergillus species isolated from patients with haematological malignancies in Tunisia; 2) compare the E-test and Sensititre Yeast-One assays for the detection of paradoxical growth and trailing effect, both phenotypes commonly exhibited by Aspergillus spp. upon exposure to caspofungin and 3) to evaluate the mortality rate in patients according to the causative Aspergillus species and the antifungal treatment.We tested amphotericin B, itraconazole, voriconazole, posaconazole and caspofungin against 48 Aspergillus isolates (17, A. niger; 18, A. flavus; 9, A. tubingensis; 1, A. westerdijkiae; and 1, A. ochraceus) with the E-test. Minimal inhibition concentrations were above the epidemiological cut-off values for amphotericin B in 67% of A. flavus strains; for caspofungin in 22% of A. flavus strains; and for itraconazole in 22% of A. tubingensis strains, voriconazole and posaconazole MICs were below the epidemiological cut-off values for all strains.When exposed to caspofungin, 42% of the strains exhibited trailing effect and 38% paradoxical growth. Trailing effect occurred in 61% of A. flavus strains and paradoxical growth in 62% of Aspergillus section Nigri strains. E-test and Sensititre Yeast-One assays were only fairly concordant for the detection of these phenotypes. Repeatability of both assays was high for trailing effect but poor for paradoxical growth. The relatively high frequency of amphotericin B resistant strains makes voriconazole best adapted as a first-line treatment of invasive aspergillosis from amphotericin B to voriconazole in this hospital.
Highlights
Invasive aspergillosis (IA) is a life threatening infection, especially in neutropenic patients where it is associated with a high mortality rate (Montagna et al, 2012; Blot et al, 2012)
The aims of our study were to evaluate the in vitro antifungal susceptibility profile of Aspergillus spp. strains isolated from patients with haematological malignancies by using the E-test method, to assess both E-testTM and Sensititre Yeast-OneTM (SYO) assays for the detection of paradoxical growth (PG) and trailing effect (TE) phenotypes exhibited by Aspergillus spp. upon exposure to CS and to evaluate the mortality rate in patients according to the causative Aspergillus species and the antifungal treatment
Twelve (66.6%) A. flavus isolates had amphotericin B (AMB) minimum inhibitory concentration (MIC) above the corresponding Epidemiologic cut-off values (ECV), indicating that these isolates have acquired a resistance to AMB
Summary
Invasive aspergillosis (IA) is a life threatening infection, especially in neutropenic patients where it is associated with a high mortality rate (Montagna et al, 2012; Blot et al, 2012). Over the last two decades, new antifungal agents including azoles and caspofungin were developed in order to improve the prognosis of IA. Tests for Aspergillus spp. in vitro antifungal susceptibility testing were developed and commercialized (Pfaller, 2012). The extensive use of antifungal agents was associated with the emergence of azole-resistant Aspergillus spp., and caspofungin (CS) has been recommended as a salvage treatment of IA (Pfaller et al, 2008; Jarque et al, 2013). Epidemiologic cut-off values (ECVs) of the MIC were established for different Aspergillus species and different antifungal agents, in order to assess the emergence of strains with decreased susceptibility (Espinel-Ingroff et al, 2011a, Espinel-Ingroff et al 2011b). A wild type organism being defined as a strain which does not harbor any acquired resistance to the particular antimicrobial agent being examined (Pfaller et al, 2011)
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