TY - JOUR
T1 - How does antifungal pharmacology differ for mucormycosis versus aspergillosis?
AU - Lewis, Russell E.
AU - Lortholary, Olivier
AU - Spellberg, Brad
AU - Roilides, Emmanuel
AU - Kontoyiannis, Dimitrios P.
AU - Walsh, Thomas J.
N1 - Funding Information:
Potential conflicts of interest. R. L. has received grant support from Merck & Co, Gilead, Astellas, and Enzon. O. L. has received grant support from Gilead and Astellas; has been a consultant for Astellas; and has served on the speakers’ bureaus of Astellas, Gilead, Pfizer, Schering-Plough, and Merck. B. S. has received grant support from Gilead, Astellas, and Novartis; has been a consultant for Merck, Pfizer, Arpida, Theravance, Advanced Life Sciences, Basilea, The Medicines Company, Novo Nordisk, Novartis, and Cerexa; and is a shareholder of NovaDigm Therapeutics and Neutropenia Immunotherapy Solutions. T. J .W. has received grant support from Novartis and Astellas and has been a consultant for Trius, iCo, Sigma Tau, Draius, and Novartis. D. K. has served on the boards of and received consultancy support from Schering-Plough and Merck. E. R. has been a consultant for Schering, Gilead, Astellas, Cephalon, Pfizer, Wyeth, Merck, and Aventis and has served on the lecture/speakers’ bureaus of Pfizer, Gilead, Enzon, Schering, and Wyeth.
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Over the last decade, advances in diagnostic systems and the introduction of new antifungal agents have significantly improved outcomes in immunocompromised patients who develop invasive aspergillosis. However, mortality rates remain relatively unchanged for less common, but highly aggressive, mold infections such as mucormycosis. Recent genome sequencing of Rhizopus oryzae revealed evidence of a whole-genome duplication event during the evolution of this pathogen. Consequently, R. oryzae has a 2- to 10-fold enrichment in gene families associated with ergosterol and cell wall biosynthesis, cell growth, iron uptake, and known fungal virulence factors compared with sequenced Aspergillus fumigatus strains. This genetic plasticity may explain the remarkable capability of this pathogen for rapid growth in hostile environments, such as the inflammatory milieu, as well as its relative resistance to multiple antifungal classes. Herein, we examine how pharmacological aspects of treating mucormycosis may differ from those of the more commonly encountered invasive aspergillosis.
AB - Over the last decade, advances in diagnostic systems and the introduction of new antifungal agents have significantly improved outcomes in immunocompromised patients who develop invasive aspergillosis. However, mortality rates remain relatively unchanged for less common, but highly aggressive, mold infections such as mucormycosis. Recent genome sequencing of Rhizopus oryzae revealed evidence of a whole-genome duplication event during the evolution of this pathogen. Consequently, R. oryzae has a 2- to 10-fold enrichment in gene families associated with ergosterol and cell wall biosynthesis, cell growth, iron uptake, and known fungal virulence factors compared with sequenced Aspergillus fumigatus strains. This genetic plasticity may explain the remarkable capability of this pathogen for rapid growth in hostile environments, such as the inflammatory milieu, as well as its relative resistance to multiple antifungal classes. Herein, we examine how pharmacological aspects of treating mucormycosis may differ from those of the more commonly encountered invasive aspergillosis.
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U2 - 10.1093/cid/cir884
DO - 10.1093/cid/cir884
M3 - Article
C2 - 22247448
AN - SCOPUS:84855864796
SN - 1058-4838
VL - 54
SP - S67-S72
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - SUPPL. 1
ER -