Abstract:In vitro susceptibility testing of Fusarium is becoming increasingly important because of frequency and diversity of infections and because resistance profiles are species-specific. Reference methods for antifungal susceptibility testing (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints (BPs) have not yet been established. One of the problems is that phylogenetic distances between Fusarium species are much sma… Show more
“…The echinocandins and azoles had no activity; the only antifungal compound with low MICs against some strains was amphotericin B. Other authors have reported different patterns according to the species complexes; thus, Fusarium solani isolates are usually resistant to azoles and show higher MICs of amphotericin B than other species, whereas Fusarium oxysporum and Fusarium verticillioides can be susceptible to voriconazole and posaconazole (35). In our study, most isolates (9 out of 13) were identified as Fusarium proliferatum (Fusarium fujikuroi complex); a study analyzing 81 strains of the Fusarium fujikuroi complex found that amphotericin B was the most active drug, followed by voriconazole, posaconazole, isavuconazole, and natamycin, while fluconazole, itraconazole, and micafungin showed poor activity (36).…”
Antifungal resistance is increasing by the emergence of intrinsically resistant species and by the development of secondary resistance in susceptible species. A previous study performed in Spain revealed levels of azole resistance in molds of between 10 and 12.7%, but secondary resistance in was not detected. We used itraconazole (ITZ)-supplemented medium to select resistant strains. A total of 500 plates supplemented with 2 mg/liter of ITZ were sent to 10 Spanish tertiary hospitals, and molecular identification and antifungal susceptibility testing were performed. In addition, the gene in those strains showing azole resistance was sequenced. A total of 493 isolates were included in the study. Sixteen strains were isolated from patients with an infection classified as proven, 104 were isolated from patients with an infection classified as probable, and 373 were isolated from patients with an infection classified as colonization. was the most frequent genus isolated, at 80.3%, followed by (7.9%), (4.5%), (2.6%), and the order (1%). Antifungal resistance was detected in species,, , and Three strains of were resistant to azoles; two of them harbored the TR+L98H mechanism of resistance, and the other one had no mutations in The level of azole resistance in remains low, but cryptic species represent over 10% of the isolates and have a broader but overall higher range of antifungal resistance.
“…The echinocandins and azoles had no activity; the only antifungal compound with low MICs against some strains was amphotericin B. Other authors have reported different patterns according to the species complexes; thus, Fusarium solani isolates are usually resistant to azoles and show higher MICs of amphotericin B than other species, whereas Fusarium oxysporum and Fusarium verticillioides can be susceptible to voriconazole and posaconazole (35). In our study, most isolates (9 out of 13) were identified as Fusarium proliferatum (Fusarium fujikuroi complex); a study analyzing 81 strains of the Fusarium fujikuroi complex found that amphotericin B was the most active drug, followed by voriconazole, posaconazole, isavuconazole, and natamycin, while fluconazole, itraconazole, and micafungin showed poor activity (36).…”
Antifungal resistance is increasing by the emergence of intrinsically resistant species and by the development of secondary resistance in susceptible species. A previous study performed in Spain revealed levels of azole resistance in molds of between 10 and 12.7%, but secondary resistance in was not detected. We used itraconazole (ITZ)-supplemented medium to select resistant strains. A total of 500 plates supplemented with 2 mg/liter of ITZ were sent to 10 Spanish tertiary hospitals, and molecular identification and antifungal susceptibility testing were performed. In addition, the gene in those strains showing azole resistance was sequenced. A total of 493 isolates were included in the study. Sixteen strains were isolated from patients with an infection classified as proven, 104 were isolated from patients with an infection classified as probable, and 373 were isolated from patients with an infection classified as colonization. was the most frequent genus isolated, at 80.3%, followed by (7.9%), (4.5%), (2.6%), and the order (1%). Antifungal resistance was detected in species,, , and Three strains of were resistant to azoles; two of them harbored the TR+L98H mechanism of resistance, and the other one had no mutations in The level of azole resistance in remains low, but cryptic species represent over 10% of the isolates and have a broader but overall higher range of antifungal resistance.
“…Novel identification tools, such as MALDI-TOF MS, or nonculture diagnostic assays, enable both accurate and fast identification of Fusarium species in the clinical laboratory: further insight into antifungal susceptibility profiles associated with each species should help to choose an adequate first-line antifungal treatment and thus improve the prognosis of invasive fusariosis patients [93]. Susceptibility testing of clinical isolates is highly recommended in the clinical setting, not only because there are significant strain-and species-specific differences in antifungal susceptibility, but also for epidemiological studies to detect emergence of resistant strains [94]. Further data from animal models and clinical trials evaluating the optimal treatment strategy against Fusarium infections are needed to refine and improve treatment guidelines, which are currently based on data from relatively large, but uncontrolled case series.…”
Fungi of the genus Fusarium are well known as major plant pathogens and soil inhabitants, but also cause a broad spectrum of human infections. Fusariosis is the second most common mould infection after aspergillosis, and keratitis is the most encountered implantation infection in immunocompetent individuals. Natamycin is active against Fusarium species both in vitro and in vivo, and is used along with voriconazole as the mainstay of treatment for Fusarium keratitis. Onychomycosis is treated with terbinafine, voriconazole and sometimes itraconazole. Cure is possible despite high in vitro minimum inhibitory concentrations (MICs). Recently, disseminated infections have increased dramatically, mainly affecting severely immunocompromised patients. The remarkable intrinsic resistance of Fusarium species to most antifungal agents results in high mortality rates in this patient population. Recovery of neutropenia is essential for patient survival and treatment should include voriconazole or amphotericin B as first-line and posaconazole as salvage therapy.
Antifungal susceptibility testing is an important tool for managing patients with invasive fungal infections, as well as for epidemiological surveillance of emerging resistance. For routine testing in clinical microbiology laboratories, ready-to-use commercial methods are more practical than homemade reference techniques. Among commercially available methods, the concentration gradient Etest strip technique is widely used. It combines an agar-based diffusion method with a dilution method that determinates a minimal inhibitory concentration (MIC) in µg/mL. Many studies have evaluated the agreement between the gradient strip method and the reference methods for both yeasts and filamentous fungi. This agreement has been variable depending on the antifungal, the species, and the incubation time. It has also been shown that the gradient strip method could be a valuable alternative for detection of emerging resistance (non-wild-type isolates) as Etest epidemiological cutoff values have been recently defined for several drug-species combinations. Furthermore, the Etest could be useful for direct antifungal susceptibility testing on blood samples and basic research studies (e.g., the evaluation of the in vitro activity of antifungal combinations). This review summarizes the available data on the performance and potential use of the gradient strip method.
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