Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B.
Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.
Walsh
Thomas J
TJ
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, NIH Building 10, Room 13N240, Bethesda, MD 20892, USA. walsht@mail.nih.gov
Petraitis
Vidmantas
V
Petraitiene
Ruta
R
Field-Ridley
Aida
A
Sutton
Deanna
D
Ghannoum
Mahmoud
M
Sein
Tin
T
Schaufele
Robert
R
Peter
Joanne
J
Bacher
John
J
Casler
Heather
H
Armstrong
Derek
D
Espinel-Ingroff
Anna
A
Rinaldi
Michael G
MG
Lyman
Caron A
CA
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D021821:Communicable Diseases, Emerging / Q000188:drug therapy / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D005260:Female; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013045:Species Specificity
D000935:Antifungal Agents; D000666:Amphotericin B