title: Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis.
abstract: An improved number of anti-fungal drugs are currently available for the treatment of invasive aspergillosis (IA). While serial galactomannan index (GMI) measurement can be used to monitor response to treatment, the extent to which different anti-fungal regimens can affect galactomannan levels is unknown. In 147 IA patients receiving either voriconazole (VCZ) or conventional amphotericin B (CAB) in a multicentre clinical trial, we performed post-hoc analyses of GMI trends in relation to outcomes. The generalized estimation equations approach was used to estimate changes in the effect size for GMI over time within patients. Patients who received VCZ primary therapy and had good treatment response 12 weeks later showed earlier decreases in GMI values at Week 1 and Week 2 (p = 0.001 and 0.046 respectively) as compared to patients who only received CAB. At end-of-randomized therapy (EORT), which was a pre-set secondary assessment point for all patients who switched from randomized primary (CAB or VCZ) to an alternative anti-fungal drug, treatment failure was associated with increasing GMI at Weeks 1 and 2 in CAB-primary treated patients (p = 0.022 and 0.046 respectively). These distinct trends highlight the variations in GMI kinetics with the use of different anti-fungal drugs and their implications in relation to IA treatment response.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands ; Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, Singapore.
authors.forename: Louis Yi Ann
authors.initials: LY
authors.lastname: Chai
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands.
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.affiliation: Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Arul
authors.initials: A
authors.lastname: Earnest
authors.affiliation: Mycology Reference Laboratory, Health Protection Agency, Bristol, United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Johnson
authors.affiliation: Department of Epidemiology, Biostatistics and Health Technology Assessment, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: Teerenstra
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.
authors.forename: Alieke G
authors.initials: AG
authors.lastname: Vonk
authors.affiliation: Pfizer Global Research and Development, New York, New York, United States of America.
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.affiliation: Department of Oncology and Hematology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands ; Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen, the Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: The Old Court, Broadstairs, Kent, United Kingdom.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Troke
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D005260:Female; D062610:Fungal Polysaccharides / Q000097:blood*; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D006801:Humans; D008297:Male; D008351:Mannans / Q000097:blood*; D011743:Pyrimidines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D062610:Fungal Polysaccharides; D008351:Mannans; D011743:Pyrimidines; D014230:Triazoles; C012990:galactomannan; D000666:Amphotericin B; D065819:Voriconazole; D005690:Galactose