Risk Adapted Management of Febrile Neutrepenia and Early Cessation of Empirical Antibiotherapy in Hematopoietic Stem Cell Transplantation Setting

Abstract

Background: Haematopoietic stem cell transplantation is a curative treatment option for many haematological disorders. Infection following haematopoietic stem cell transplantation is one of the major causes of mortality. Aims: To investigate the outcomes of early cessation of empirical antibiotic treatment per protocol in febrile neutropenia patients who have undergone haematopoietic stem cell transplantation at our clinic. Study Design: Descriptive study. Methods: The present study retrospectively evaluated febrile neutropenia attacks in haematopoietic stem cell transplantation recipients during the period June 2014 - January 2015 at our haematopoietic stem cell transplantation clinic. Results: A total of 72 febrile neutropenia attacks were evaluated in 53 patients. In 46 febrile neutropenia attacks, microbiologic cultures revealed positive results. In culture-positive febrile neutropenia episodes a single bacterium was isolated in 32 cases and multiple strains were isolated in 14. In 15 patients, empirical antibiotic therapy was discontinued after 72 hours. These patients were clinically stable, without evident focus of infection and had negative culture results. Only 4 recurrent episodes were observed (27%) after cessation of antibiotherapy. No patient died as a result of recurrent infection. The 30-day and 100-day post-transplantation mortality rates of patients with febrile neutropenia episodes were 11.3% (6/53) and 3.8% (2/53), respectively. Infection-related 30-day and 100-day mortality rates were 7.5% (4/53) and 0% (0/53), respectively. Conclusion: The main message of our study is that early cessation of empirical antibiotherapy seems to be feasible in eligible patients without increasing febrile neutropenia mortality rates.

Keywords

• Haematopoietic stem cell transplantation, febrile neutropenia, early cessation of empirical antibiotherapy

References

1. 1. Pasquini MC, Zhu X. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides, 2014. Available at: http://www. cibmtr.org.
2. 2. Basak GW, Wiktor-Jedrzejczak W, Labopin M, Schoemans H, Ljungman P, Kobbe G, et al. Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT. Am J Transplant 2015;15:705-14.
3. 3. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases Society of America. Clin Infect Dis 2011;15;52:e56-93.
4. 4. Zuckermann J, Moreira LB, Stoll P, Moreira LM, Kuchenbecker RS, Polanczyk CA. Compliance with a critical pathway for the management of febrile neutropenia and impact on clinical outcomes. Ann Hematol 2008;87:139-45.
5. 5. Sipsas NV, Bodey GP, Kontoyiannis DP. Perspectives for the management of febrile neutropenic patients with cancer in the 21st century. Cancer 2005;15;103:1103-13.
6. 6. Uys A, Rapoport BL, Anderson R. Febrile neutropenia: A prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support Care Cancer 2004;12:555- 60.
7. 7. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;15;46:1813-21.
8. 8. Barberan J, Mensa J, Llamas JC, Ramos IJ, Ruiz JC, Marín JR, et al. Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient. Rev Esp Quimioter 2011;24:263-70.

9. 9. http://www.cibmtr.org.
10. 10. Sharma A, Lokeshwar N. Febrile neutropenia in haematological malignancies. J Postgrad Med 2005;51(Suppl)1:S42-8.
11. 11. Toussaint E, Bahel-Ball E, Vekemans M, Georgala A, Al-Hakak L, Paesmans M, et al. Causes of fever in cancer patients. Support Care Cancer 2006;14:763-9.
12. 12. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 2005;8;353:977-87.
13. 13. Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 2005;142:979-95.
14. 14. Cattaneo C, Quaresmini G, Casari S, Capucci MA, Micheletti M, Borlenghi E, et al. Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: Results of a prospective study on 823 patients at a single institution. J Antimicrob Chemother 2008;61:721-8.
15. 15. Erbay MÇ, Tekgündüz E, Çimentepe M, Akay N, İskender G, Tetik A, et al. Kinolon resistance in patients with hematological malignancies. 15th Congress of Turkish Clinical Microbiology and Infectious Diseases 2011-Antalya. p:265.
16. 16. Köse Ş, Atalay S, Ödemiş İ, Adar P. Çeşitli Klinik Örneklerden İzole Edilen Pseudomonas Aeruginosa Suşlarının Antibiyotik Duyarlılıkları. ANKEM Derg 2014;28:100-4.
17. 17. Akan H. Febril Nötropeni. İç hastalıkları 1. baskı. Ed. Erol Ç. Ankara 2008; 873.
18. 18. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al; European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 2013;98:1826-35.
19. 19. Trecarichi EM, Tumbarello M, Spanu T, Caira M, Fianchi L, Chiusolo P, et al. Incidence and clinical impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies. J Infect 2009;58:299-307.
20. 20. Sigurdardottir K, Digranes A, Harthug S, Nesthus I, Tangen JM, Dybdahl B, et al. A multicentre prospective study of febrile neutropenia in Norway: microbiological fi ndings and antimicrobial susceptibility. Scand J Infect Dis 2005;37:455-64.
21. 21. Demiraslan H, Yıldız O, Kaynar L, Altuntaş F, Eser B, Aygen B. Febril nötropenik hastalardan izole edilen mikroorganizmalar ve antimikrobiyal duyarlılıkları: 2005 yılı verileri. Erciyes Tıp Derg 2007;29:376-80.
22. 22. Gur D, Hascelik G, Aydin N, Telli M, Gültekin M, Ogülnç D, et al. Antimicrobial resistance in Gram-negative hospital isolates: results of the Turkish HITIT-2 surveillance study of 2007. J Chemother 2009;21:383-9.
23. 23. Marchetti O, Lamoth F, Mikulska M, Viscoli C, Verweij P, Bretagne S. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant 2012;47:846-54.
24. 24. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, et al. Galactomannan and Computed Tomography-Based Preemptive Antifungal Therapy in Neutropenic Patients at High Risk for Invasive Fungal Infection: A Prospective Feasibility Study. Clin Infect Dis 2005;1;41:1242-50
25. 25. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis 2009;15;48:1042-51.
26. 26. Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: Epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005;40(Suppl 4):S240-5.
27. 27. Sacar S, Hacioglu SK, Keskin A, Turgut H. Evaluation of febrile neutropenic attacks in a tertiary care medical center in Turkey. J Infect Dev Ctries 2008;2:359-63.
28. 28. Pehlivan M, Demirkan F, Özsan H, Yılmaz U, Ündar B. Sitotoksik tedavi veya kemik iliği tutulumuna bağlı gelişen 148 febril nötropeni epizodu. Klimik Derg 1999;12:93.
29. 29. Savaş L, Yıldırımak T, Önlen Y, Tan-Çetmeli G, Savaş N, Efe-İris N, ve ark. Febril ve afebril hastalarda kan kültürlerinin değerlendirilmesi. Klimik Derg 2006;19:32-5.