J Korean Med Sci.  2008 Dec;23(6):941-947. 10.3346/jkms.2008.23.6.941.

Current Antimicrobial Usage for the Management of Neutropenic Fever in Korea: A Nationwide Survey

• Choi SM
• Park SH
• Lee DG
• Choi JH
• Yoo JH
• Shin WS

• KMID: 1107514
• DOI: http://doi.org/10.3346/jkms.2008.23.6.941

Abstract

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second- line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future.

Keyword

Neutropenia; Fever; Therapeutics; Guideline; Prevention and Control; Anti-Bacterial Agents; Antifungal Agents

MeSH Terms

Administration, Oral
Aminoglycosides/therapeutic use
Amphotericin B/therapeutic use
Anti-Bacterial Agents/*therapeutic use
Antifungal Agents/therapeutic use
Cephalosporins/therapeutic use
Data Collection
Deoxycholic Acid/therapeutic use
Drug Combinations
Drug Therapy, Combination
Fever/*drug therapy/etiology
Fluoroquinolones/therapeutic use
Hematopoietic Stem Cell Transplantation
Humans
Korea
Neoplasms/drug therapy
Neutropenia/*drug therapy
Prospective Studies
Questionnaires
Time Factors
Treatment Failure

Figure

• 

  Fig. 1 Process of data collection.

Reference

1. 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. 34:730–751.

2. Link H, Bohme A, Cornely OA, Hoffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW. Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Antimicrobial therapy of unexplained fever in neutropenic patients. guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol. 2003. 82:Suppl 2. S105–S117.

3. Biron P, Fuhrmann C, Escande MC, Blanc-Vincent MP, Crokaert F, Beal J, Bussy V, Lesimple T, Pottecher B, Raveneau J, Senet JM, Viot M. Standards, Options, and Recommendations for the management of brief neutropenias. Fedération Nationale des Centres de Lutte Contre le Cancer. Bull Cancer. 1998. 85:695–711.

4. Viscoli C, Castagnola E, Caniggia M, De Sio L, Garaventa A, Giacchino M, Indolfi P, Izzi GC, Manzoni P, Rossi MR, Santoro N, Zanazzo GA, Masera G. Italian guidelines for the management of infectious complications in pediatric oncology: empirical antimicrobial therapy of febrile neutropenia. Oncology. 1998. 55:489–500.

5. Proceedings of the consensus meeting: evidence-based recommendations on the management of febrile neutropenia in Japan. Honolulu, Hawaii, 8-9 March 2003. Clin Infect Dis. 2004. 39:Suppl 1. S1–S69.

6. Song YG, Chang KH, Kim HY, Hong SK, Park YS, Cho JH, Kim CO, Huh AJ, Park ES, Kim YS, Choi YW, Kim JM. Evaluation for appropriateness of therapeutic use of antibiotics in patients with respiratory tract infections and in patients with febrile neutropenia. J Korean Soc Chemother. 2000. 18:125–140.

7. Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. 2005. 142:979–995.

8. Hori S, Sunley R, Tami A, Grundmann H. The Nottingham Staphylococcus aureus Population Study: prevalence of MRSA among the elderly in a university hospital. J Hosp Infect. 2002. 50:25–29.

9. Yoo JH, Huh DH, Choi JH, Shin WS, Kang MW, Kim CC, Kim DJ. Molecular epidemiological analysis of quinolone-resistant Escherichia coli causing bacteremia in neutropenic patients with leukemia in Korea. Clin Infect Dis. 1997. 25:1385–1391.

10. Lee DG, Choi SM, Choi JH, Yoo JH, Park YH, Kim YJ, Lee S, Min CK, Kim HJ, Kim DW, Lee JW, Min WS, Shin WS, Kim CC. Selective bowel decontamination for the prevention of infection in acute myelogenous leukemia: a prospective randomized trial. Korean J Intern Med. 2002. 17:38–44.

11. Furno P, Bucaneve G, Del Favero A. Monotherapy or aminoglycoside containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis. Lancet Infect Dis. 2002. 2:231–242.

12. Paul M, Soares-Weiser K, Leibovici L. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis. BMJ. 2003. 326:1111.

13. Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, Gallagher J, Herrstedt J, Rapoport B, Rolston K, Talcott J. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000. 18:3038–3051.

14. Vidal L, Paul M, Ben-Dor I, Pokroy E, Soares-Weiser K, Leibovici L. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev. 2004. 4:CD003992.

15. Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC), International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group. J Infect Dis. 1991. 163:951–958.

16. Paul M, Borok S, Fraser A, Vidal L, Leibovici L. Empirical antibiotics against Gram-positive infections for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2005. 55:436–444.

17. Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999. 340:764–771.

18. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004. 351:1391–1402.

19. Kerr JP, Liakopolou E, Brown J, Cornish JM, Fleming D, Massey E, Oakhill A, Pamphilon DH, Robinson SP, Totem A, Valencia AM, Marks DI. The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogeneic stem cell transplantation. Br J Haematol. 2003. 123:114–118.

20. Mousset S, Hermann S, Klein SA, Bialleck H, Duchscherer M, Bomke B, Wassmann B, Bohme A, Hoelzer D, Martin H. Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Ann Hematol. 2005. 84:734–741.

21. Price TH. Granulocyte transfusion: current status. Semin hematol. 2007. 44:15–23.

22. Park SH, Choi SM, Lee DG, Choi JH, Yoo JH, Shin WS, Kang MW. Efficacies and safeties on granulocyte transfusion for severe infections during neutropenic fever. Infect Chemother. 2004. 36(S2):S153.