Abstract
The aim of this study is to compare the curative effect of empirical with diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients (SAAs) with invasive fungal disease (IFD) after intensive immunosuppressive therapy (IST). Patients undergoing voriconazole antifungal therapy were randomized to empirical therapy group and diagnostic-driven therapy group. Empirical therapy group accounted for 48.5% of all cases, and diagnostic-driven therapy group accounted for 51.5%. The morbidity of IFD (probable and proven cases) was slightly increased in diagnostic-driven therapy group compared with empirical therapy group (P > 0.05). The total effective rate was 62.1%. The effective rate in empirical therapy group was 78.1%, which was significantly increased compared with diagnostic-driven therapy group (47.1%) (P < 0.05). This value was especially significant in possible IFD cases (P < 0.05). The efficacy of possible IFD cases in empirical therapy group was the best (84%) followed by the probable and proven cases in empirical therapy group (57.1%). In diagnostic-driven therapy group, the efficacy of possible IFD cases was 50%, and the efficacy of probable and proven cases was only 37.5%. The difference was statistically significant (P < 0.05). Absolute neutrophil count (ANC) is the key anti-infection factor. The efficacy of patients whose ANC ˂ 0.1 × 109/L was 39.28%, which was significantly reduced compared with that of patients whose ANC ≥ 0.1 × 109/L (78.95%) (P < 0.05). This finding was especially obvious in diagnostic-driven therapy group. As empirical therapy is superior to diagnostic-driven therapy, we recommend that empirical therapy should be started for high-risk patients, and efforts should be made to definitively diagnose the disease.
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References
Shan W et al (2018) Fungal infection caused by Geotrichum capitatum in a severe aplastic anemia patient: a case report and review of the literature. Clin Lab 64(5):867–869
Samanta A et al (2019) Clinical profile and microbiological spectrum of febrile neutropenic episodes in children with severe aplastic anemia. J Pediatr Hematol Oncol
Marsh JC et al (2009) Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 147(1):43–70
Donnelly JP et al (2019) Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the mycoses study group education and research consortium. Clin Infect Dis
Groll AH et al (2014) Fourth European conference on infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol 15(8):e327–e340
Okuturlar Y et al (2015) Serum galactomannan levels in the diagnosis of invasive aspergillosis. Korean J Intern Med 30(6):899–905
Chinese Invasive Fungal Infection Working, G (2017) The Chinese guidelines for the diagnosis and treatment of invasive fungal disease in patients with hematological disorders and cancers (the fifth revision). Zhonghua Nei Ke Za Zhi 56(6):453–459
Pappas PG et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62(4):e1–e50
Koch E, Rada G (2016) Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia? Medwave 16(Suppl 2):e6463
Drgona L et al (2014) Clinical and economic burden of invasive fungal diseases in Europe: focus on pre-emptive and empirical treatment of Aspergillus and Candida species. Eur J Clin Microbiol Infect Dis 33(1):7–21
Wu YH et al (2003) The clinical features of severe aplastic anemia patients with complication of infection. Zhonghua Xue Ye Xue Za Zhi 24(10):530–533
Patterson TF et al (2016) Executive summary: practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 63(4):433–442
Wilson DT, Drew RH, Perfect JR (2009) Antifungal therapy for invasive fungal diseases in allogeneic stem cell transplant recipients: an update. Mycopathologia 168(6):313–327
Yuan W et al (2016) Preemptive antifungal therapy for febrile neutropenic hematological malignancy patients in China. Med Sci Monit 22:4226–4232
Maertens JA et al (2016) The current management landscape: aspergillosis. J Antimicrob Chemother 71(suppl 2):ii23–ii29
Dib RW et al (2018) Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies. BMC Infect Dis 18(1):656
Santolaya ME et al (2018) Efficacy of pre-emptive versus empirical antifungal therapy in children with cancer and high-risk febrile neutropenia: a randomized clinical trial. J Antimicrob Chemother 73(10):2860–2866
Funding
This work was supported by grants from the National Natural Science Foundation of China (81700118, 81870101, 81800119, 81800120, 81700117, 81900125) and Natural Science Foundation of Tianjin City (18ZXDBSY00140, 17JCQNJC11500).
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Wu, Y., Yan, L., Wang, H. et al. Clinical study on empirical and diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients with invasive fungal disease after intensive immunosuppressive therapy. Eur J Clin Microbiol Infect Dis 40, 949–954 (2021). https://doi.org/10.1007/s10096-020-04054-9
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DOI: https://doi.org/10.1007/s10096-020-04054-9