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

• Published in: The Journal of infection 2015-08, Vol.71 (2), p.258-265
• Main Authors: Hasseine, Lilia, Cassaing, Sophie, Robert-Gangneux, Florence, Fillaux, Judith, Marty, Pierre, Gangneux, Jean-Pierre
• Format: Article
• Language: English
• Subjects: Adult; Antifungal stewardship program; Antifungals; Aspergillus galactomannan; Blood - microbiology; DNA, Fungal - genetics; DNA, Fungal - isolation & purification; DNA, Ribosomal Spacer - genetics; DNA, Ribosomal Spacer - isolation & purification; Drug Monitoring - methods; Empirical treatment; Female; Fungemia - diagnosis; Fungemia - drug therapy; Humans; Infectious Disease; Invasive aspergillosis; Invasive fungal infection; Life Sciences; Male; Middle Aged; Molecular Diagnostic Techniques - methods; Panfungal PCR; PCR; Predictive Value of Tests; Prospective Studies; Real-Time Polymerase Chain Reaction - methods; Reevaluation; Secondary Prevention - methods; Treatment Outcome; Young Adult
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2015.04.005

Summary 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.