Abstract
BackgroundA 73-year-old female suffering from acute myeloid leukemia presented with progressive rhinofacial mycosis. Suspecting it to be mucormycosis, the antifungal amphotericin B (AMB) was administered empirically, but the patient did not respond as planned. The fungus was then isolated from the biopsied tissue and morphologically identified as a species of Aspergillus. Necrosis progressed and she died of cerebral hemorrhage. Since Aspergillus flavus is susceptible to AMB, and several other Aspergillus species can be misidentified as A. flavus, the observed resistance necessitated a re-examination of the fungal isolate.MethodsThe fungal strain was re-isolated and re-examined morphologically. Additionally, genomic DNA was extracted from the fungus and sequences were obtained from three genomic regions [the rDNA internal transcribed spacer (ITS) region, and portions of the β-tubulin and calmodulin genes] to more accurately identify this Aspergillus strain. Its antifungal susceptibility was assessed using multiple compounds and our findings were compared with literature data.ResultsThe fungal culture again yielded an Aspergillus isolate morphologically identical to A. flavus. Molecular analyses, however, revealed the strain to be A. nomiae, a close relative of A. flavus in section Flavi, and it exhibited resistance to AMB. Reviewing the literature, only five other cases of A. nomiae infection in humans have been reported worldwide.Conclusion and Clinical ImportanceThe rhinofacial mycosis of the patient was actually due to A. nomiae. The initial misidentification of the fungus, coupled with its resistance to AMB, could be the reason treatment did not help the patient. We postulate that clinical A. nomiae infections may be underreported and that accurate and speedy pathogen identification is important so that an effective antifungal regimen can be administered.
Highlights
Invasive aspergillosis, i.e., deep infections by an Aspergillus species, are among the most common opportunistic mold infections that can cause potentially life-threatening disease in those with chronic neutropenia, or inherited or acquired immunodeficiencies, as well as in those undergoing allogeneic hematopoietic stem cell transplant, solid organ transplant, or prolonged corticosteroid use (Li et al, 2008; Patterson et al, 2016)
Second only to Aspergillus fumigatus for lung infections and rhino-(facial)orbital-cerebral mycosis (ROCM) (Alsalman et al, 2017; Rudramurthy and Paul, 2019; Hu et al, 2021), Aspergillus flavus is the most frequently encountered species in invasive sinusitis (Bakhshaee et al, 2016; Alsalman et al, 2017); in 9% of cases of ROCM, A. flavus is listed as the causal organism (Hu et al, 2021), while other species have remained unidentified in the literature (Hu et al, 2021)
Clinical outcomes of treatment of aspergilloses have markedly improved with the availability of newer triazoles, the development of resistance to triazoles in A. fumigatus and the intrinsic resistance to polyenes in A. flavus is a growing concern (Rudramurthy and Paul, 2019; Wiederhold and Verweij, 2020)
Summary
I.e., deep infections by an Aspergillus species, are among the most common opportunistic mold infections that can cause potentially life-threatening disease in those with chronic neutropenia, or inherited or acquired immunodeficiencies, as well as in those undergoing allogeneic hematopoietic stem cell transplant, solid organ transplant, or prolonged corticosteroid use (Li et al, 2008; Patterson et al, 2016). Given that A. flavus shares a similar morphology with other closely related species, potential misidentification of an isolate as A. flavus is an issue. With high morphological similarities, conserved loci most often help to delineate species of fungi (Houbraken et al, 2020). A 73-year-old female suffering from acute myeloid leukemia presented with progressive rhinofacial mycosis. Suspecting it to be mucormycosis, the antifungal amphotericin B (AMB) was administered empirically, but the patient did not respond as planned. The fungus was isolated from the biopsied tissue and morphologically identified as a species of Aspergillus. Necrosis progressed and she died of cerebral hemorrhage. Since Aspergillus flavus is susceptible to AMB, and several other Aspergillus species can be misidentified as A. flavus, the observed resistance necessitated a re-examination of the fungal isolate
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