title: Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis.
abstract: Early and accurate diagnosis of invasive aspergillosis (IA) is one of the most critical steps needed to efficiently treat the infection and reduce the high mortality rates that can occur. We have previously found that the Aspergillus spp. secondary metabolite, bis(methylthio)gliotoxin (bmGT), can be detected in the serum from patients with possible/probable IA. Thus, it could be used as a diagnosis marker of the infection. However, there is no data available concerning the sensitivity, specificity and performance of bmGT to detect the infection. Here, we have performed a prospective study comparing bmGT detection with galactomannan (GM), the most frequently used and adopted approach for IA diagnosis, in 357 sera from 90 episodes of patients at risk of IA. Our results, involving 79 patients that finally met inclusion criteria, suggest that bmGT presents higher sensitivity and positive predictive value (PPV) than GM and similar specificity and negative predictive value (NPV). Importantly, the combination of GM and bmGT increased the PPV (100 %) and NPV (97.5 %) of the individual biomarkers, demonstrating its potential utility in empirical antifungal treatment guidance and withdrawal. These results indicate that bmGT could be a good biomarker candidate for IA diagnosis and, in combination with GM, could result in highly specific diagnosis of IA and management of patients at risk of infection.
authors.affiliation: Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain. matvigar@gmail.com.
authors.forename: Matxalen
authors.initials: M
authors.lastname: Vidal-García
authors.affiliation: Instituto de Carboquímica, ICB-CSIC, Zaragoza, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Domingo
authors.affiliation: Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: De Rueda
authors.affiliation: Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Roc
authors.affiliation: Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Delgado
authors.affiliation: Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Revillo
authors.affiliation: Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|Centro de Investigación Biomédica de Aragón (CIBA), Zaragoza, Spain.|Aragon I+D Foundation, Zaragoza, Spain.|University of Zaragoza, Zaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
authors.affiliation: Instituto de Carboquímica, ICB-CSIC, Zaragoza, Spain.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Gálvez
authors.affiliation: Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain.|Fundación Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.|University of Zaragoza, Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rezusta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D005912:Gliotoxin / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis*; D008297:Male; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D008351:Mannans; C451025:methylthiogliotoxin; C012990:galactomannan; D005912:Gliotoxin; D005690:Galactose
keywords: Bis(methylthio)gliotoxin; Diagnostic accuracy; Galactomannan; Gliotoxin; Invasive aspergillosis