Evaluation of Antifungal Treatment Strategies in Febrile Neutropenic Episodes of High-Risk Hematologic Malignancies: A Single Center Retrospective Study

Year 2025, Volume: 7 Issue: 1, 12 - 21, 29.01.2025

Aycan Acet , Vildan Ozkocaman , Fahir Özkalemkaş

https://doi.org/10.46310/tjim.1602618

Abstract

Background Febrile neutropenic patients are at high risk for developing invasive fungal infection (IFI). Currently, two treatment strategies, empiric and preemptive, are used in febrile neutropenic patients with IFI. This study aimed to evaluate empirical and preemptive treatment strategies in patients with high-risk hematologic malignancies.
Methods We retrospectively analyzed 402 febrile neutropenic attacks in 281 patients with hematological malignancies hospitalized in a university hospital hematology clinic. Between June 2006 and January 2009, 154 febrile neutropenic episodes of 104 patients who met the study eligibility criteria were included. Patients who received antibiotic and antifungal treatment for febrile neutropenia were retrospectively recorded. Patients treated with empiric and preemptive approaches were identified and compared with statistical methods.
Results Antifungal treatment was initiated as empiric treatment in 62 (40%), preemptive therapy in 55 (36%) (subgroups; 45 [29%] possible-IFI and 10 [7%] probable-IFI), and 37 (24%) for secondary prophylaxis. In terms of length of hospitalization and all-cause mortality, no statistically significant results were found when patients receiving empiric and preemptive treatment were compared. (p>0.05).
Conclusion In patients with high-risk hematologic malignancies, even if empiric treatment is initiated, a dynamic approach that can be summarized as persistently trying to obtain evidence by using ancillary diagnostic tools and early termination of therapy in unnecessary cases seems appropriate.

Keywords

febrile neutropenia, invasive fungal infections, empiric-preemptive therapy, High-risk hematologic malignancy

Ethical Statement

The study protocol was approved by the Medical Ethics Committee of Uludağ University Faculty of Medicine (Decision number: 2009-3/39).

References

• Ascioglu S, de Pauw BE, Meis JF. Prophylaxis and treatment of fungal infections associated with haematological malignancies. Int J Antimicrob Agents. 2000 Aug;15(3):159-68. doi: 10.1016/s0924-8579(00)00159-x.
• von Eiff M, Roos N, Schulten R, Hesse M, Zühlsdorf M, van de Loo J. Pulmonary aspergillosis: early diagnosis improves survival. Respiration. 1995;62(6):341-7. doi: 10.1159/000196477.
• Reichenberger F, Habicht J, Matt P, Frei R, Solèr M, Bolliger CT, Dalquen P, Gratwohl A, Tamm M. Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis. Bone Marrow Transplant. 1999 Dec;24(11):1195-1199. doi: 10.1038/sj.bmt.1702045.
• De Pauw BE, Deresinski SC, Feld R, Lane-Allman EF, Donnelly JP. Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group. Ann Intern Med. 1994 May 15;120(10):834-44. doi: 10.7326/0003-4819-120-10-199405150-00004.
• Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003 May 1;36(9):1103-1110. doi: 10.1086/374339.
• Pauw B, Walsh TJ, Donnely P, et al. Revised Definitions of İnvasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Insitute of Allergy and Infectıous Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Inf Dis 2008;46:1813-21
• Febrile Neutropenia Study Group: Guidelines for the diagnosis and treatment of febrile neutropenic patients. Flora. 2004;9:5-28 (in Turkish).
• Rieger CT, Ostermann H. Empiric vs. preemptive antifungal treatment: an appraisal of treatment strategies in haematological patients. Mycoses. 2008;51 Suppl 1:31-4. doi: 10.1111/j.1439-0507.2008.01526.x.
• Wingard JR. Empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis. 2004 Jul 15;39 Suppl 1:S38-43. doi: 10.1086/383052.
• Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982 Jan;72(1):101-11. doi: 10.1016/0002-9343(82)90594-0.
• Mahfouz T, Anaissie E. Prevention of fungal infections in the immunocompromised host. Curr Opin Investig Drugs. 2003 Aug;4(8):974-90.
• Soyer N, Kiper Ünal HD, Vural F, Şahin F, Töbü M, Dönmez A, Tombuloğlu M, Arda B, Saydam G. Epidemiology and analysis of invasive fungal infections in patients withhematological malignancies: a single-center real-life experience. Turk J Med Sci. 2017 Nov 13;47(5):1535-1542. doi: 10.3906/sag-1611-90.
• Pagano L, Caira M, Nosari A, Cattaneo C, Fanci R, Bonini A, Vianelli N, Garzia MG, Mancinelli M, Tosti ME, Tumbarello M, Viale P, Aversa F, Rossi G; HEMA e-Chart Group. The use and efficacy of empirical versus pre-emptive therapy in the management of fungal infections: the HEMA e-Chart Project. Haematologica. 2011 Sep;96(9):1366-1370. doi: 10.3324/haematol.2011.042598.
• Fung M, Kim J, Marty FM, Schwarzinger M, Koo S. Meta-analysis and cost comparison of empirical versus pre-emptive antifungal strategies in hematologic malignancy patients with high-risk febrile neutropenia. PLoS One. 2015 Nov 10;10(11):e0140930. doi: 10.1371/journal.pone.0140930.
• Uzun Ö. Preemptive antifungal treatment. Ankem Derg. 2007;21(Suppl 2):220-3 (in Turkish).
• Maertens J, Deeren D, Dierickx D, Theunissen K. Preemptive antifungal therapy: still a way to go. Curr Opin Infect Dis. 2006 Dec;19(6):551-6. doi: 10.1097/QCO.0b013e3280106854.
• Yuan W, Ren J, Guo X, Guo X, Cai S. Preemptive antifungal therapy for febrile neutropenic hematological malignancy patients in China. Med Sci Monit. 2016 Nov 7;22:4226-4232. doi: 10.12659/msm.897596.
• Cordonnier C, Robin C, Alanio A, Bretagne S. Antifungal pre-emptive strategy for high-risk neutropenic patients: why the story is still ongoing. Clin Microbiol Infect. 2014 Jun;20 Suppl 6:27-35. doi: 10.1111/1469-0691.12428.
• Otting KA, Stover KR, Cleary JD. Drug-laboratory interaction between beta-lactam antibiotics and the galactomannan antigen test used to detect mould infections. Braz J Infect Dis. 2014;18(5):544-7. doi:10.1016/j.bjid.2014.03.009.
• Vergidis P, Razonable RR, Wheat LJ, Estes L, Caliendo AM, Baden LR, Wingard JR, Baddley J, Assi M, Norris S, Chandrasekar P, Shields R, Nguyen H, Freifeld A, Kohler R, Kleiman M, Walsh TJ, Hage CA. Reduction in false-positive Aspergillus serum galactomannan enzyme immunoassay results associated with use of piperacillin-tazobactam in the United States. J Clin Microbiol. 2014 Jun;52(6):2199-2201. doi: 10.1128/JCM.00285-14.
• Salehi M, Ghaderkhani S, Sharifian RA, Dehghan Manshadi SA, Samiee Fard E, Khodavaisy S, Pourahmad R, Foroushani AR, Rodini K, Kamali Sarvestani H. The value of nasal and oral clinical examination in febrile neutropenic patients for ınitiating antifungal therapy as a preemptive method. Front Med (Lausanne). 2022 Jan 28;8:803600. doi: 10.3389/fmed.2021.803600.
• Fung M, Kim J, Marty FM, Schwarzinger M, Koo S. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia. PLoS One. 2015 Nov 10;10(11):e0140930. doi: 10.1371/journal.pone.0140930.
• Walker BS, Schmidt RL, Tantravahi S, Kim K, Hanson KE. Cost-effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant. Transpl Infect Dis. 2019 Oct;21(5):e13148. doi: 10.1111/tid.13148.
• Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002 Mar 15;34(6):730-51. doi: 10.1086/339215.
• Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002 Mar 15;34(6):730-51. doi: 10.1086/339215.
• Goldberg E, Gafter-Gvili A, Robenshtok E, Leibovici L, Paul M. Empirical antifungal therapy for patients with neutropenia and persistent fever: Systematic review and meta-analysis. Eur J Cancer. 2008 Oct;44(15):2192-2203. doi: 10.1016/j.ejca.2008.06.040.
• Akan H. EORTC definitions in fungal infections. Ankem Derg. 2009;23(Suppl.2):130-4 (in Turkish).