title: Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD.
abstract: 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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: U
authors.initials: U
authors.lastname: Gergis
authors.forename: K
authors.initials: K
authors.lastname: Markey
authors.forename: J
authors.initials: J
authors.lastname: Greene
authors.forename: M
authors.initials: M
authors.lastname: Kharfan-Dabaja
authors.forename: T
authors.initials: T
authors.lastname: Field
authors.forename: G
authors.initials: G
authors.lastname: Wetzstein
authors.forename: M J
authors.initials: MJ
authors.lastname: Schell
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: J
authors.initials: J
authors.lastname: Perkins
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D005938:Glucocorticoids; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D015725:Fluconazole; D065819:Voriconazole
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