Antifungal therapy in haematology patients: Empirical or preemptive ?

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3ème Atelier Thématique en Hématologie (ATHEM ) 22 novembre 2013. Antifungal therapy in haematology patients: Empirical or preemptive ?. Dr S. Alfandari Médecin Référent en antibiothérapie et Hygiéniste, CH Tourcoing Infectiologue Consultant, Service des Maladies du sang, CHRU Lille - PowerPoint PPT Presentation

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3me Atelier Thmatique en Hmatologie (ATHEM)22 novembre 2013 Dr S. AlfandariMdecin Rfrent en antibiothrapie et Hyginiste, CH TourcoingInfectiologue Consultant, Service des Maladies du sang, CHRU Lillewww.infectio-lille.comAntifungal therapy in haematology patients:Empirical or preemptive ?

1Lectures: Gilead, MSD, Novartis, PfizerMeetings: Gilead, MSD, Pfizer, SanofiFrench ID society administrator: Astellas - Astra Zeneca - Gilead - Viiv Healthcare - Janssen Cilag - MSD - Sanofi Pasteur MSD - Pfizer - Bayer Pharma - BMS - Abbott - Roche - Novartis Vitalaire - Biofilm control - GSK - CelestisPotential conflicts of interestAll haematology patientsNo, thats prophylaxis

Haematology patients with mycological evidence of IFINo, thats targeted treatment

Febrile neutropenia patients Yes, but which patients ?What treatment are we talking about ?Standard of care since the 2002 IDSA guidelinesSupporting studies Pizzo et al. AMJ 198250 patients with fever & 7 days broad spectrum AB randomized toAB stop/continuing AB/ AB + amphotericin BInfections: 9/6/2EORTC. AMJ 1989132 patients with fever & 4 days AB randomized w - w/o AmB1,5% (n=1) vs 9% IFI (n=6)No significant difference in overall mortalityEmpirical antifungal therapy in febrile neutropenia patientsThree large trials: similar results - few events

ProEarly IFI RxAnother step in antimicrobial therapyMight delay escalation therapy to carbapenemsPsychological support: we DO something to treat the feverConMost patients receive unnecessary Rx: no infection/no IFIAdverse eventsCostsNew diagnostic tools allow for early diagnosisPro/con empirical AF therapyDecreasing IFI risk in haematology patients90s17-25% in AML/allograft (Bodey, EJCMID 1992, Guiot CID 1994)00s~10% in AML (Nosary, AJH 2001, Cornely, NEJM 2007) and allograft (Ullmann, NEJM 2007)Including arms without mould-active prophylaxis from randomized trials10sUnfrequent event with generalized mould-active prophylaxis5 d or pulm infiltrate:B- Empirical antifungal therapy (n=207)Persistent fever >5 d (w ou w/o PCR+) or pulm infiltratePCR-Based Preemptive Antifungal TherapyHebart et al BMT 2009;43: 553-61PCREmpiricalpN treated112 (57.1%)76 (36.7%)0.003N proven/probable IFI1617NSN death D304 (1.5%)13 (6.3%)0.015N total death D1003234NSDrug: AmB or AmB-L daily / CrClEmpirical armFever drivenPre-emptive armPneumonia, shock, skin lesions evocative of IFI, sinusitis, orbititis, hepatosplenic abscesses, grade 4 mucositis, Aspergillus colonization, or one GM Ag +Multiple criteria based Preemptive Antifungal TherapyCordonnier et al CID 2009 48:104251Multiple criteria based Preemptive Antifungal TherapyEmpirical (N=150)Preemptive (N=143)P Fever before ATF (d) 713