title: Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.
abstract: Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.|Stanford University School of Medicine, Stanford, CA.
authors.forename: M
authors.initials: M
authors.lastname: Mansh
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.
authors.forename: M
authors.initials: M
authors.lastname: Binstock
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.
authors.forename: K
authors.initials: K
authors.lastname: Williams
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.
authors.forename: F
authors.initials: F
authors.lastname: Hafeez
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
authors.forename: D
authors.initials: D
authors.lastname: Glidden
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, CA.
authors.forename: R
authors.initials: R
authors.lastname: Boettger
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: S
authors.initials: S
authors.lastname: Hays
authors.affiliation: Department of Surgery, University of California, San Francisco, CA.
authors.forename: J
authors.initials: J
authors.lastname: Kukreja
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: J
authors.initials: J
authors.lastname: Golden
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland, CA.
authors.forename: M M
authors.initials: MM
authors.lastname: Asgari
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: P
authors.initials: P
authors.lastname: Chin-Hong
authors.affiliation: Department of Medicine, University of California, San Francisco, CA.
authors.forename: J P
authors.initials: JP
authors.lastname: Singer
authors.affiliation: Department of Dermatology, University of California, San Francisco, CA.
authors.forename: S T
authors.initials: ST
authors.lastname: Arron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents; D001228:Aspergillosis / Q000139:chemically induced* / Q000453:epidemiology / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000139:chemically induced* / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D066027:Transplant Recipients; D065819:Voriconazole / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole