Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD.
Patients on systemic glucocorticoids for GVHD after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole or fluconazole vs itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD who were administered voriconazole (n=97), fluconazole (n=36) or itraconazole (n=36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole vs 2/97 (2%) on voriconazole (P=0.03) within the first 100 days of glucocorticoids. Five (7%) patients developed Aspergillus IFI on fluconazole/itraconazole, compared with none on voriconazole (0%) (P=0.008); Aspergillus IFI resulted in death in all five patients. We found that IFI occurred in patients who received an initial dose of at least 2 mg/kg/day of prednisone or equivalent; when the analysis was restricted to these patients, the hazard ratio (0.39; 95% confidence interval: 0.08-1.86) was consistent with a protective effect of voriconazole compared with fluconazole/itraconazole, although this subset analysis did not reach significance. OS at 100 days after start of glucocorticoids was 77% in patients administered fluconazole/itraconazole and 85% in those administered voriconazole (P=0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids post transplant.
Gergis
U
U
Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Markey
K
K
Greene
J
J
Kharfan-Dabaja
M
M
Field
T
T
Wetzstein
G
G
Schell
M J
MJ
Huang
Y
Y
Anasetti
C
C
Perkins
J
J
D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D005938:Glucocorticoids / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D005938:Glucocorticoids; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D015725:Fluconazole; D065819:Voriconazole
Ann Intern Med. 2003 May 6;138(9):705-13
12729424
J Infect Dis. 1997 Jun;175(6):1459-66
9180187
Blood. 2002 Dec 15;100(13):4358-66
12393425
Antimicrob Agents Chemother. 1998 Jan;42(1):161-3
9449278
Antimicrob Agents Chemother. 2002 Aug;46(8):2546-53
12121931
Clin Infect Dis. 2008 Oct 15;47(8):1041-50
18781877
Clin Infect Dis. 1999 Feb;28(2):331-40
10064252
Haematologica. 2006 Jul;91(7):986-9
16757415
N Engl J Med. 1992 Mar 26;326(13):845-51
1542320
Blood. 2000 Sep 15;96(6):2055-61
10979947
Blood. 2004 Feb 15;103(4):1527-33
14525770
Clin Infect Dis. 2003 Jan 1;36(1):9-15
12491195
Blood. 2010 Dec 9;116(24):5111-8
20826719
Biol Blood Marrow Transplant. 1999;5(2):55-68
10371357
Clin Infect Dis. 2002 Jan 1;34(1):7-14
11731939
J Infect Dis. 1995 Jun;171(6):1545-52
7769290
N Engl J Med. 2007 Jan 25;356(4):335-47
17251530
J Clin Pharmacol. 2002 Apr;42(4):395-402
11936564
Blood. 2003 Aug 1;102(3):827-33
12689933
Biol Blood Marrow Transplant. 2006 Jul;12(7):734-48
16785063