Background: Invasive aspergillosis has become a leading cause of infectious mortality in recipients of hematopoietic stem cell transplantation (HSCT), prompting investigation of prophylaxis and early diagnosis strategies. Given the high risk for subsequent invasion in HSCT recipients colonized with A. fumigatus, empiric therapy has become common. This study was performed to determine itraconazole susceptibilities and genotypes of isolates recovered from HSCT recipients, with an emphasis on comparison of sequential colonizing and invasive clinical isolates. Methods: Itraconazole susceptibilities of 85 A. fumigatus isolates collected from HSCT recipients between 10/98 and 7/00 were determined using Etests, with confirmation using the NCCLS method. Strain discrimination of sequential isolates was performed by PCR amplification of intergenic spacer regions between ribosomal DNA transcription units. Results: Itraconazole MICs, determined using Etest, ranged from 0.094 to 1mg/mL and correlated with NCCLS results. Genotypes of 34 isolates from14 series of colonizing and invasive isolates, and isolates obtained from sequential invasive sites (i.e. lung and brain), were compared. Three distinct patterns were recognized in the series of invasive isolates, with one genotype responsible for the majority (58%). All colonizing and invasive isolates within patients were genetically similar, even among those obtained from the patient at different times. Conclusions: Itraconazole resistance appears infrequently, although one matched series of susceptible and resistant isolates was identified. Genetic similarity is maintained among sequential colonizing and invasive isolates in HSCT recipients. The predominance of one genotype among invasive isolates suggests the presence of a particularly virulent strain, although further studies are required to confirm this observation.
Full conference title:
- ICAAC 41st