title: High negative predictive value diagnostic strategies for the reevaluation of early antifungal treatment: A multicenter prospective trial in patients at risk for invasive fungal infections.
abstract: Early antifungal therapeutic strategies are proposed during invasive fungal infection (IFI), but antifungal stewardship programs should institute a systematic reevaluation of prescriptions, particularly in the context of empirical treatment. Here, we aimed to evaluate the performances and particularly the negative predictive value (NPV) of diagnostic strategies, including a whole blood panfungal quantitative PCR assay (PF-qPCR) in a high risk population for IFI. The first step was to standardize and optimize a new PF-qPCR targeting ITS2 region. Then, this method was evaluated in a multicenter prospective study including 313 patients with suspected IFI for whom an early antifungal treatment was prescribed. All patients enrolled at day 0 of their treatment benefited from serum Aspergillus galactomannan (GM) antigen detection twice a week, weekly PF-qPCR assay, and when indicated and feasible, CT-scan and mycological sampling. In total, 125 of 313 patients were diagnosed with IFI: 68 invasive aspergillosis (eight proven, 48 probable and 12 possible), one fusariosis, 47 candidemia, three disseminated candidiasis and six cryptococcosis. Globally, the sensitivity of the PF-qPCR assay was only 40%, but the specificity, PPV and NPV were 96%, 88% and 69%, respectively. In the population of patients at high risk for invasive aspergillosis who also benefited from Aspergillus GM detection, the sensitivity and the NPV of the combined detection reached to 78% and 84%, respectively. Even higher NPV were obtained when combining negative PF-qPCR and CT scan (95%) as well as negative GM and CT scan (93%), thus allowing to rationalize and re-evaluate the prescription of empirical treatment in such highly selected population.
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Nice, France. Electronic address: Hasseine.l@chu-nice.fr.
authors.forename: Lilia
authors.initials: L
authors.lastname: Hasseine
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cassaing
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Rennes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Robert-Gangneux
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Toulouse, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Fillaux
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Nice, Université Nice Sophia Antipolis, Unité Inserm U 1065, Equipe 6, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marty
authors.affiliation: Laboratoire de Parasitologie-Mycologie, CHU de Rennes, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gangneux
mesh_terms: D000328:Adult; D001769:Blood / Q000382:microbiology*; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D021903:DNA, Ribosomal Spacer / Q000235:genetics / Q000302:isolation & purification; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D016469:Fungemia / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D055502:Secondary Prevention / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer
keywords: Antifungal stewardship program; Antifungals; Aspergillus galactomannan; Empirical treatment; Invasive aspergillosis; Invasive fungal infection; PCR; Panfungal PCR; Reevaluation