PMID- 25896093 OWN - NLM STAT- MEDLINE DCOM- 20160321 LR - 20191210 IS - 1532-2742 (Electronic) IS - 0163-4453 (Linking) VI - 71 IP - 2 DP - 2015 Aug TI - 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. PG - 258-65 LID - S0163-4453(15)00098-5 [pii] LID - 10.1016/j.jinf.2015.04.005 [doi] AB - 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. CI - Copyright (c) 2015. Published by Elsevier Ltd. FAU - Hasseine, Lilia AU - Hasseine L AD - Laboratoire de Parasitologie-Mycologie, CHU de Nice, France. Electronic address: Hasseine.l@chu-nice.fr. FAU - Cassaing, Sophie AU - Cassaing S AD - Laboratoire de Parasitologie-Mycologie, CHU de Toulouse, France. FAU - Robert-Gangneux, Florence AU - Robert-Gangneux F AD - Laboratoire de Parasitologie-Mycologie, CHU de Rennes, France. FAU - Fillaux, Judith AU - Fillaux J AD - Laboratoire de Parasitologie-Mycologie, CHU de Toulouse, France. FAU - Marty, Pierre AU - Marty P AD - Laboratoire de Parasitologie-Mycologie, CHU de Nice, Universite Nice Sophia Antipolis, Unite Inserm U 1065, Equipe 6, France. FAU - Gangneux, Jean-Pierre AU - Gangneux JP AD - Laboratoire de Parasitologie-Mycologie, CHU de Rennes, France. CN - PF-qPCR Study Group LA - eng PT - Evaluation Study PT - Journal Article PT - Multicenter Study DEP - 20150418 PL - England TA - J Infect JT - The Journal of infection JID - 7908424 RN - 0 (DNA, Fungal) RN - 0 (DNA, Ribosomal Spacer) SB - IM MH - Adult MH - Blood/*microbiology MH - DNA, Fungal/genetics/isolation & purification MH - DNA, Ribosomal Spacer/genetics/isolation & purification MH - Drug Monitoring/*methods MH - Female MH - Fungemia/*diagnosis/*drug therapy MH - Humans MH - Male MH - Middle Aged MH - Molecular Diagnostic Techniques/*methods MH - Predictive Value of Tests MH - Prospective Studies MH - Real-Time Polymerase Chain Reaction/*methods MH - Secondary Prevention/*methods MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Antifungal stewardship program OT - Antifungals OT - Aspergillus galactomannan OT - Empirical treatment OT - Invasive aspergillosis OT - Invasive fungal infection OT - PCR OT - Panfungal PCR OT - Reevaluation FIR - Sirvent, Anne IR - Sirvent A FIR - Mondain, Veronique IR - Mondain V FIR - Hyvernat, Herve IR - Hyvernat H FIR - Rosenthal, Eric IR - Rosenthal E FIR - Cointault, Olivier IR - Cointault O FIR - Lavayssiere, Laurence IR - Lavayssiere L FIR - Georges, Bernard IR - Georges B FIR - Berry, Antoine IR - Berry A FIR - de Guibert, Sophie IR - de Guibert S FIR - Nimubona, Stanislas IR - Nimubona S FIR - Revest, Matthieu IR - Revest M FIR - Tattevin, Pierre IR - Tattevin P EDAT- 2015/04/22 06:00 MHDA- 2016/03/22 06:00 CRDT- 2015/04/22 06:00 PHST- 2014/07/07 00:00 [received] PHST- 2015/03/09 00:00 [revised] PHST- 2015/04/10 00:00 [accepted] PHST- 2015/04/22 06:00 [entrez] PHST- 2015/04/22 06:00 [pubmed] PHST- 2016/03/22 06:00 [medline] AID - S0163-4453(15)00098-5 [pii] AID - 10.1016/j.jinf.2015.04.005 [doi] PST - ppublish SO - J Infect. 2015 Aug;71(2):258-65. doi: 10.1016/j.jinf.2015.04.005. Epub 2015 Apr 18.