title: Efficacy of liposomal amphotericin B and posaconazole in intratracheal models of murine mucormycosis.
abstract: Mucormycosis is a life-threatening fungal infection almost uniformly affecting diabetics in ketoacidosis or other forms of acidosis and/or immunocompromised patients. Inhalation of Mucorales spores provides the most common natural route of entry into the host. In this study, we developed an intratracheal instillation model of pulmonary mucormycosis that hematogenously disseminates into other organs using diabetic ketoacidotic (DKA) or cyclophosphamide-cortisone acetate-treated mice. Various degrees of lethality were achieved for the DKA or cyclophosphamide-cortisone acetate-treated mice when infected with different clinical isolates of Mucorales. In both DKA and cyclophosphamide-cortisone acetate models, liposomal amphotericin B (LAmB) or posaconazole (POS) treatments were effective in improving survival, reducing lungs and brain fungal burdens, and histologically resolving the infection compared with placebo. These models can be used to study mechanisms of infection, develop immunotherapeutic strategies, and evaluate drug efficacies against life-threatening Mucorales infections.
authors: Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, California, USA.
authors: Guanpingsheng
authors: G
authors: Luo
authors: Teclegiorgis
authors: T
authors: Gebremariam
authors: Hongkyu
authors: H
authors: Lee
authors: Samuel W
authors: SW
authors: French
authors: Nathan P
authors: NP
authors: Wiederhold
authors: Thomas F
authors: TF
authors: Patterson
authors: Scott G
authors: SG
authors: Filler
authors: Ashraf S
authors: AS
authors: Ibrahim
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003348:Cortisone / Q000031:analogs & derivatives; D003520:Cyclophosphamide; D016883:Diabetic Ketoacidosis / Q000139:chemically induced; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D008826:Microbial Sensitivity Tests; D009090:Mucorales / Q000187:drug effects*; D009091:Mucormycosis / Q000188:drug therapy* / Q000382:microbiology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C068538:liposomal amphotericin B; C101425:posaconazole; D000666:Amphotericin B; D003520:Cyclophosphamide; D003348:Cortisone
references: J Clin Invest. 1984 Jul;74(1):150-60
references: 6736246
references: Antimicrob Agents Chemother. 2004 May;48(5):1908-11
references: 15105158
references: Clin Infect Dis. 2012 Feb;54 Suppl 1:S35-43
references: 22247443
references: PLoS One. 2012;7(7):e40908
references: 22911715
references: Antimicrob Agents Chemother. 2012 May;56(5):2246-50
references: 22290952
references: Mycopathologia. 1990 May;110(2):87-91
references: 2142253
references: Antimicrob Agents Chemother. 2008 Apr;52(4):1556-8
references: 18212099
references: Clin Infect Dis. 2006 Apr 1;42(7):e61-5
references: 16511748
references: Clin Microbiol Rev. 2000 Apr;13(2):236-301
references: 10756000
references: J Natl Cancer Inst. 1998 Aug 5;90(15):1130-7
references: 9701362
references: Clin Infect Dis. 2000 Jun;30(6):851-6
references: 10852735
references: Antimicrob Agents Chemother. 2010 Mar;54(3):1055-9
references: 20065054
references: Clin Microbiol Infect. 2011 Dec;17(12):1859-67
references: 21199154
references: Leuk Lymphoma. 2004 Jul;45(7):1351-60
references: 15359632
references: Clin Infect Dis. 2003 Jul 15;37(2):221-9
references: 12856215
references: Clin Infect Dis. 2002 Apr 1;34(7):909-17
references: 11880955
references: J Antimicrob Chemother. 2012 Jul;67(7):1712-5
references: 22427614
references: N Engl J Med. 2012 Dec 6;367(23):2214-25
references: 23215557
references: Kidney Int. 1994 Mar;45(3):667-71
references: 8196268
references: Clin Pharmacokinet. 1995 Jan;28(1):41-66
references: 7712661
references: Curr Opin Infect Dis. 2011 Dec;24(6):521-6
references: 21799406
references: Transplantation. 2010 Nov 27;90(10):1133-5
references: 21427635
references: Antimicrob Agents Chemother. 2001 Dec;45(12):3474-81
references: 11709327
references: Clin Infect Dis. 2012 Feb;54 Suppl 1:S16-22
references: 22247441
references: Gut. 1978 Dec;19(12):1153-62
references: 217803
references: Clin Infect Dis. 2012 Feb;54 Suppl 1:S44-54
references: 22247444
references: Clin Cancer Res. 2007 Aug 15;13(16):4900-8
references: 17699870
references: J Antimicrob Chemother. 2003 Jan;51(1):45-52
references: 12493786
references: J Antimicrob Chemother. 2012 Mar;67(3):715-22
references: 21937481
references: J Clin Invest. 2010 Jun;120(6):1914-24
references: 20484814
references: Int J Surg Pathol. 2011 Feb;19(1):75-9
references: 19168908
references: Mycopathologia. 2013 Feb;175(1-2):99-106
references: 23124364
references: J Antimicrob Chemother. 2010 Oct;65(10):2158-63
references: 20667887
references: Clin Infect Dis. 2004 Aug 15;39(4):588-90
references: 15356828
references: Antimicrob Agents Chemother. 2003 Nov;47(11):3647-50
references: 14576138
references: Postgrad Med J. 2009 Nov;85(1009):573-81
references: 19892892
references: Clin Microbiol Rev. 2011 Apr;24(2):411-45
references: 21482731
references: Am Fam Physician. 2008 Jun 15;77(12):1697-702
references: 18619079
references: Lancet. 2005 Mar 5-11;365(9462):876-8
references: 15752532
references: J Infect Dis. 1984 Nov;150(5):752-60
references: 6387001
references: J Clin Invest. 1993 May;91(5):1979-86
references: 8486769
references: J Clin Microbiol. 2009 Dec;47(12):3862-70
references: 19759217
references: Antimicrob Agents Chemother. 2008 Apr;52(4):1573-6
references: 18227182
references: Antimicrob Agents Chemother. 2003 Oct;47(10):3343-4
references: 14506054
references: Antimicrob Agents Chemother. 2009 Feb;53(2):772-5
references: 18936190
references: PLoS Genet. 2009 Jul;5(7):e1000549
references: 19578406
references: Clin Infect Dis. 2005 Sep 1;41(5):634-53
references: 16080086
references: Antimicrob Agents Chemother. 2008 Oct;52(10):3786-8
references: 18694953
references: Clin Infect Dis. 2012 Feb;54 Suppl 1:S23-34
references: 22247442
references: Antimicrob Agents Chemother. 2002 May;46(5):1581-2
references: 11959605
references: Antimicrob Agents Chemother. 2005 Feb;49(2):721-7
references: 15673756
references: Clin Microbiol Rev. 2005 Jul;18(3):556-69
references: 16020690
references: J Infect Dis. 2009 May 1;199(9):1399-406
references: 19358672
references: Infect Immun. 2005 Feb;73(2):778-83
references: 15664916
references: Med Mycol. 2012 Oct;50(7):710-5
references: 22458251
references: J Clin Invest. 2007 Sep;117(9):2649-57
references: 17786247
references: Infect Immun. 1984 Apr;44(1):194-5
references: 6706405
references: Antimicrob Agents Chemother. 2002 Jul;46(7):2310-2
references: 12069997
references: Int J Antimicrob Agents. 2011 Dec;38(6):465-73
references: 21782392
references: Clin Infect Dis. 2003 Jun 1;36(11):1488-91
references: 12766845