Invasive aspergillosis due to Neosartorya udagawae.
BACKGROUND
Invasive aspergillosis (IA) is most commonly caused by the morphospecies Aspergillus fumigatus. However, genetic-based methods indicate that organisms phenotypically identified as A. fumigatus actually constitute a mold complex, designated Aspergillus section fumigati subgenus fumigati.


METHODS
Multilocus sequencing and analysis was performed on fungi identified as A. fumigatus from the clinical culture collection maintained at the National Institutes of Health from 2000 through 2008, with a focus on the internal transcribed spacer 1 and 2 regions of ribosomal DNA (rDNA), beta-tubulin, and rodlet A genes. We reviewed the medical records, radiology, and histopathology of corresponding patients. To confirm identification of Neosartorya udagawae isolates, mating studies were performed with reference strains. Antifungal susceptibility testing was performed by broth microdilution and read at 48 hours.


RESULTS
Thirty-six cases of infection attributed to A. fumigatus were identified; 4 were caused by N. udagawae (3 in patients with chronic granulomatous disease and 1 in a patient with myelodysplastic syndrome). Disease due to N. udagawae was chronic, with a median duration of 35 weeks, compared with a median duration of 5.5 weeks for patients with chronic granulomatous disease who had infection due to A. fumigatus sensu stricto (P < .05 , Mann-Whitney U test). Infection spread across anatomical planes in a contiguous manner and was refractory to standard therapy. Two of the 4 patients died. N. udagawae demonstrated relatively higher minimum inhibitory concentrations to various agents, compared with those demonstrated by contemporary A. fumigatus sensu stricto isolates.


CONCLUSIONS
To our knowledge, this is the first report documenting infection due to N. udagawae. Clinical manifestations were distinct from those of typical IA. Fumigati-mimetics with inherent potential for antifungal resistance are agents of IA. Genetic identification of molds should be considered for unusual or refractory IA.
Vinh
Donald C
DC
Sections of Immunopathogenesis, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892-1684, USA.
Shea
Yvonne R
YR
Sugui
Janyce A
JA
Parrilla-Castellar
Edgardo R
ER
Freeman
Alexandra F
AF
Campbell
J William
JW
Pittaluga
Stefania
S
Jones
Pamela A
PA
Zelazny
Adrian
A
Kleiner
David
D
Kwon-Chung
Kyung J
KJ
Holland
Steven M
SM
D000328:Adult; D000818:Animals; D016172:DNA Fingerprinting / Q000379:methods; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000737:chemistry / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D005838:Genotype; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000382:microbiology*; D008297:Male; D008826:Microbial Sensitivity Tests; D016533:Mycological Typing Techniques; D009181:Mycoses / Q000382:microbiology*; D055326:Neosartorya / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D013902:Radiography, Thoracic; D017422:Sequence Analysis, DNA; D014404:Tubulin / Q000235:genetics
D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer; D005656:Fungal Proteins; D014404:Tubulin