Clinical efficacy and management of primary antifungal prophylaxis with posaconazole in high-risk haematology patients

Isabel Sánchez-Ortega*, Isabel Cuesta, Beatriz Patiño, Rocío Parody, Montserrat Arnan, Alberto Fernández de Sevilla, Carlota Gudiol, Josefina Ayats, Manuel Cuenca-Estrella, Rafael F. Duarte

Author address: 

Barcelona, Majadahonda, Madrid, Sevilla, ES

Abstract: 

We have previously reported the use of posaconazole antifungal prophylaxis in a small series of 33 early phase alloHCT [BMT2011; 46(5):733-9]. Now, we present our experience on the efficacy and clinical management of primary antifungal prophylaxis with posaconazole in 262 consecutive high-risk episodes (161 AML-chemotherapy, 79 alloHCT and 22 grade II-IV GVHD) from 123 hematology patients prospectively included in a single-center study (2007-2011; CEIC Bellvitge; EPA 008/08). Our management algorithm included a comprehensive diagnostic approach for patients with persistent fever (CT scans, microbiological samples and cultures from urine, blood, BAL and other infected sites), as well as preemptive serum galactomannan (GM) tests twice weekly from the start of the risk episodes. Breakthrough IFD as per EORTC criteria occurred in 10 episodes (3.8%, Table 1): 5 invasive candidiasis (1.9%; 3 glabrata, 2 tropicalis) and 5 invasive aspergillosis (IA=1.9%; 1 proven, 4 probable), 8 after AML-chemotherapy and 2 in alloHCT/GVHD, leading to 4 IFD-related deaths (1.5%). Of note, 2 cases of IA occurred during an outbreak and co-infection with H1N1. Posaconazole was substituted for IV antifungal therapy in 34 additional episodes (13.0%) based on an individualized clinical judgment for persistent fever, intolerance or side-effects. The vast majority of episodes (218, 83.2%) completed posaconazole prophylaxis as planned. A total of 2972 serum GM tests were performed in this study (median 11 per episode, 3-30), and were all negative in the majority of episodes (188, 71.7%). Positive GM results contributed to the diagnosis of all 5 episodes of IA reported. Also, positive GM tests were documented in 30 additional episodes (11.4%) where patients remained on posaconazole prophylaxis, alive, and never developed other criteria of IFD. Such false positive (FP) GM tests (1-6 per episode; optical index 0.59-6.11) were more common when performed preemptively in asymptomatic cases (26, 86.7%) than as part of a diagnostic workup in persistently febrile symptomatic patients (4, 13.3%; p<0.001). Our results confirm the efficacy of posaconazole prophylaxis in high-risk hematology patients in real-life clinical practice. They also suggest that, in this context of very effective anti-mold prophylaxis with a low incidence of IA, serum GM should be preferably used as part of diagnostic algorithms for symptomatic cases, rather than as a preemptive surveillance in asymptomatic patients.

Tables: 

2013

Full conference title: 

Annual Meeting of European Society for Blood and Marrow Transplantation
    • EBMT 39th (2013)