Disseminated Amphotericin-Resistant Fusariosis in Acute Leukemia Patients: Report of Two Cases

Abstract

Disseminated fusariosis has emerged as a significant, usually fatal infection in immunocompromised hosts despite antifungal treatment. We describe here two patients with acute leukemia who developed disseminated amphotericin-resistant fusariosis, and review of six studies of cases series in the literature. Two Fusarium solani strains were isolated from blood and skin cultures of one patient, and one strain from the blood culture of the second patient. Both patients died despite antifungal treatment. Strains were identified by sequencing of ITS1 and ITS4 regions. Random amplified polymorphic DNA analysis of the three F. solani isolates showed a low degree of similarity. Screening for Fusarium spp. contaminants within our facility was negative. Using the CLSI M-38-A2 broth dilution method and E tests(®), we found that the MICs were low for voriconazole (0.12 and 0.5 mg/L, respectively), unexpectedly high for amphotericin B (≥8 and ≥32 μg/mL, respectively) and itraconazole (≥16 mg/ml). Patients with leukemia or persistent neutropenia should be assessed for disseminated fungal infections, including biopsy and skin cultures. Antifungal susceptibility tests are important due to the possibility of the strains being amphotericin resistant. Treatments must be aggressive, with high doses of antifungals or combined therapy.

Fusarium napiforme systemic infection: case report with molecular characterization and antifungal susceptibility tests

“…However, it is controversial, since there are reports of Fusarium showing MICs for AMB ranging from 1 to 4 μg/mL. Triazoles, as voriconazole and posaconazole, have also been used successfully (Pereira et al 2013; Tortorano et al 2008). Furthermore, different Fusarium can exhibit variable susceptibility patterns.…”

“…Conversely, immunocompromised hosts, mainly those with acute onco-hematological diseases or after allogeneic hematopoietic stem cell transplant, have high risk of invasive life-threatening diseases. In such patients, invasive fusariosis (IF) is relatively resistant to standard antifungal therapy limiting their treatment options (Scheel et al 2013; Pereira et al 2013). …”

Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic Fusarium Species: Fusarium Multi-Drug Resistant Pattern

“…MDR resistance in Fusarium can be classified into: Intrinsic resistance: the innate ability of a Fusarium species to resist activity of an antifungal agent through its inherent structural or functional characteristics without prior exposure to the drug, which allows tolerance of a drug or antifungal class. It occurs naturally in Fusarium species that have never been susceptible to that agent [ 25 , 35 , 36 ]. Acquired resistance: used to describe the resistance that arises in Fusarium after exposure to the antifungal agent.…”

Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana

“…The fact that the incidence of resistance to AmB in fungi has been slow to emerge, in spite of over 50 years of use [14], has underpinned a belief that the fitness costs associated with any resistance might protect against the problem [15]. However, there are increasing reports of AmB resistance in fungi [16–18]. Moreover, several reports of AmB treatment failure have been reported in leishmaniasis patients in India [19, 20] and in immunocompromised patients in France [21] and resistance to the drug has been reported to occur in at least one field isolate already [19].…”