title: Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions.
abstract: BACKGROUND
  To assess the performance of Candida albicans germ tube antibody (CAGTA), (1 → 3)-ß-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC).
  
  
  METHODS
  A prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay ≥ 7 days. CAGTA (cutoff positivity ≥ 1/160), BDG (≥80, 100 and 200 pg/mL), mannan-Ag (≥60 pg/mL), mannan-Ab (≥10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11).
  
  
  RESULTS
  The combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2-98.0) sensitivity, 42.1 % (95 % CI 35.2-98.8) specificity, and 96.6 % (95 % CI 90.5-98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7-90.1) sensitivity and 57.2 % (95 % CI 49.9-64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity.
  
  
  CONCLUSIONS
  Positive Candida albicans germ tube antibody and (1 → 3)-ß-D-glucan in a single blood sample or (1 → 3)-ß-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Valme, Universidad de Sevilla, Avenida Bellavista s/n, 41014, Sevilla, Spain. cleong@telefonica.net.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: León
authors.affiliation: Intensive Care Unit, Hospital Universitario Dr. Negrín, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz-Santana
authors.affiliation: Mathematics Department, Universidad de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Saavedra
authors.affiliation: Clinical Unit of Microbiology and Infectious Diseases, Hospital Universitario de Valme, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Castro
authors.affiliation: Intensive Care Unit, Hospital Universitario de Valme, Universidad de Sevilla, Avenida Bellavista s/n, 41014, Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Loza
authors.affiliation: Clinical Unit of Microbiology and Infectious Diseases, Hospital Universitario de Valme, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Ismail
authors.initials: I
authors.lastname: Zakariya
authors.affiliation: Intensive Care Unit, Hospital Punta de Europa, Algeciras, Cádiz, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Úbeda
authors.affiliation: Clinical Unit of Microbiology and Infectious Diseases, Hospital Universitario de Valme, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Parra
authors.affiliation: Intensive Care Unit, Hospital Universitario de Valme, Universidad de Sevilla, Avenida Bellavista s/n, 41014, Sevilla, Spain.
authors.forename: Desirée
authors.initials: D
authors.lastname: Macías
authors.affiliation: Intensive Care Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Tomás
authors.affiliation: Service of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rezusta
authors.affiliation: Critical Care Department, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Service of Microbiology, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Gómez
authors.affiliation: Clinical Unit of Microbiology and Infectious Diseases, Hospital Universitario de Valme, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Martín-Mazuelos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal; D000935:Antifungal Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D058365:Candidiasis, Invasive / Q000175:diagnosis* / Q000401:mortality; D016638:Critical Illness / Q000401:mortality / Q000451:nursing; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000908:Antibodies, Fungal; D000935:Antifungal Agents; D015415:Biomarkers; D008351:Mannans
keywords: (1 → 3)-ß-D-glucan; Anti-mannan antibody; Candida PCR; Candida albicans germ tube antibody; Candida spp. colonization; Candidemia; Intra-abdominal candidiasis; Invasive candidiasis; Mannan antigen