Diagnostic-driven antifungal treatment in high-risk patients receiving allogeneic hematopoietic stem cell transplantation (HSCT)

A. Busca1, A. Barbui2, G. Limerutti3, C. Frairia4, C. Pecoraro4, F. Locatelli4, B. Allione4, S. d’Ard305;`a4 and M. Falda4

Author address: 

1San Giovanni Battista Hospital and University, Italy, 2Laboratory of Microbiology, San Giovanni Battista Hospital, Italy, 3First Service of Radiology, San Giovanni Battista Hospital, Italy and 4Haematology 2, San Giovanni Battista Hospital and Un

Abstract: 

Empirical antifungal treatment (AFT) has been considered a standard practice in HSCT recipients with persisting febrile neutropenia, but may be associated with the risk of overtreatment with unnecessary drugs. For these reasons several preemptive strategies have been proposed based on the incorporation of positive serum tests, microbiological criteria, radiological findings and clinical features, however there is no a standardized diagnostic approach that has gained widespread acceptance. Objectives: to prospectively investigate the impact of CT scan and non-culturebased microbiological tests as diagnostic tools for guiding early AFT. Methods: Between february 2004 and april 2011, 263 patients with hematological malignancies received an allogeneic HSCT from matched siblings (n = 117), partially matched related (n = 16) or unrelated volunteer donors (n = 130). Overall, 234 (89%) patients received fluconazole as antifungal prophylaxis, 18 (7%) patients with a previous history of invasive fungal disease (IFD) received secondary anti-fungal prophylaxis with mold-active agents, while 11 (4%) patients received different prophylactic regimens. All patients were screened twice weekly for galactomannan (GM) antigenemia from day 0 until day 100; a positive result was defined as "¡2 consecutive serum GM using a threshold of "¡0.5. Lung CT scan was performed after 3 days of fever unresponsive to broadspectrum antibiotics; bronchoscopy with bronchoalveolar lavage (BAL) was pursued in patients without severe hypoxemia and biopsy for histological diagnosis was undertaken whenever feasible. Findings that triggered AFT were: (i) CT scan suggestive of IFD ± positive GM test; (ii) biopsy/culture proven IFD. Results: Of the 263 patients, 42 (16%) experienced IFD: 16 (6%) patients had possible, 19 (7%) probable and 7 (3%) proven IFD based on revised definitions of the criteria for IFD by the EORTC/MSG. Among the seven patients with proven IFD, three had candidemia (n = 2 C. albicans; n = 1 C. guilliermondii), two had invasive aspergillosis (n = 1 Aspergillus fumigatus; n = 1 Aspergillus flavus), 1 had zygomycosis and 1 had oesophageal invasive candidiasis. Among 263 patients, 43 (16%) actually followed a diagnostic-driven treatment strategy. AFT was guided by CT findings suggestive of IFD in association with a positive GM test in 20 patients: GM assay was positive in serum (16 cases), BAL fluid (three cases) and liquor (1 case). Imaging-documented IFD (n = 13 lung CT; n = 1 sinus CT; n = 1 hepatic CT) led to ATF in 15 cases, histologic evaluation and culture triggered the
2011

abstract No: 

P089

Full conference title: 

Trends in Medical Mycology, 5th
    • TIMM 5th (2013)