Molecular Characterization and Antifungal Susceptibility of Clinical Fusarium Species From Brazil

Abstract

Fusarium is widely distributed in the environment and is involved with plant and animal diseases. In humans, several species and species complexes (SC) are related to fusariosis, i.e., F. solani SC, F. oxysporum SC, F. fujikuroi SC, F. dimerum, F. chlamydosporum, F. incarnatum-equiseti , and F. sporotrichoides . We aimed to investigate the susceptibility of Fusarium clinical isolates to antifungals and azole fungicides and identify the species. Forty-three clinical Fusarium isolates were identified by sequencing translation elongation factor 1-alpha ( TEF1 α) gene. Antifungal susceptibility testing was performed to the antifungals amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, and the azole fungicides difenoconazole, tebuconazole, and propiconazole. The isolates were recovered from patients with median age of 36 years (range 2–78 years) of which 21 were female. Disseminated fusariosis was the most frequent clinical form ( n = 16, 37.2%) and acute lymphoblastic leukemia ( n = 7; 16.3%) was the most commonly underlying condition. A few species described in Fusarium solani SC have recently been renamed in the genus Neocosmospora , but consistent naming is yet not possible. Fusarium keratoplasticum FSSC 2 ( n = 12) was the prevalent species, followed by F. petroliphilum FSSC 1 ( n = 10), N. gamsii FSSC 7 ( n = 5), N. suttoniana FSSC 20 ( n = 3), F. solani sensu stricto FSSC 5 ( n = 2), Fusarium sp. FSSC 25 ( n = 2), Fusarium sp. FSSC 35 ( n = 1), Fusarium sp. FSSC18 ( n = 1), F. falciforme FSSC 3+4 ( n = 1), F. pseudensiforme ( n = 1), and F. solani f. xanthoxyli ( n = 1). Amphotericin B had activity against most isolates although MICs ranged from 0.5 to 32 μg mL -1 . Fusarium keratoplasticum showed high MIC values (8–>32 μg mL -1 ) for itraconazole, voriconazole, posaconazole, and isavuconazole. Among agricultural fungicides, difenoconazole had the lowest activity against FSSC with MICs of >32 μg mL -1 for all isolates.

A 23 bp cyp51A Promoter Deletion Associated With Voriconazole Resistance in Clinical and Environmental Isolates of Neocosmospora keratoplastica

“…AMB and VRC MICs are values for 100% growth inhibition and the listed ITC and POS MICs are the values for 80% growth inhibition.Thirteen of the 25 FSSC isolates were classified as N. keratoplastica (FSSC 2), five as N. falciformis (FSSC 3+4), six as N. suttoniana (FSSC 20), and one as N. petroliphila (FSSC 1) (Table 1). As expected(Espinel-Ingroff et al, 2016;Herkert et al, 2019), all 25 FSSC isolates had very high (>32 mg/l) MICs for the long-tailed azoles, ITC, and POS. Initially, the susceptibility of 15 clinical FSSC isolates to ITC was measured and all isolates showed very high MIC ITC s (>32 mg/l), and so we predicted the same or higher MIC ITC s in FSSC environmental isolates.…”

“…Most Fusarium species have low susceptibilities to the majority of azole antifungals (Tupaki-Sreepurna et al, 2017;Rotjanapan et al, 2018;Herkert et al, 2019) and patients with IFs have high mortality rates (Esnakula et al, 2013;Silva et al, 2013;Okada et al, 2018). Voriconazole (VRC) and amphotericin B (AMB) are the recommended treatment options for localised infections and IFs (Efeİris et al, 2016;Okada et al, 2018).…”

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

“…Herkert et al reported that the use of sequencing translation elongation factor 1-alpha gene showed a good ability to distinguish and differentiate clinical Fusarium species. 206 Therefore, since Fusarium species cause disseminated infections in patients with hematologic malignancies and these infections are resistant to antifungal treatments, before starting immunosuppressive drugs, patients should be carefully investigated for the presence of infections that involve skin or nail, and more attention should be paid to the cutaneous lesions to reduce the risk of infections by these microorganisms in patients with blood malignancies. Of note, more clinical studies are needed to evaluate the precise function of antifungal agents to inhibit Fusarium species, because proper prophylaxis and treatment of patients with hematologic malignancies may prevent disseminated fusariosis with high mortality in these patients.…”

In Vitro Susceptibility of Fusarium to Isavuconazole

“…Our results also confirm previous studies regarding the poor in vitro efficacy of ISA against Fusarium spp. (14,15,23,24). Indeed, using the EUCAST reference method, the MIC 50 of our panel of strains was Ͼ16 mg/ml.…”

“…Isavuconazole (ISA), the last azole derivative marketed, has a more suitable safety profile than voriconazole and is now recommended at grade AI as first-line therapy for invasive aspergillosis by the European Conference on Infections in Leukemia (13). However, data on in vitro efficacy of ISA against Fusarium remain limited (14,15). Most of the previous studies used the Clinical and Laboratory Standards Institute (CLSI) reference method and included a limited number of strains, strains representing a limited number of species, or strains only identified at the species complex level.…”