Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
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Posaconazole for Prophylaxis of Fungal Infection in Pediatric Patients with Acute Myeloid Leukemia undergoing Induction Chemotherapy

소아 급성골수성백혈병에서 관해유도 요법 중 Posaconazole의 예방적 항진균 치료

  • Kim, Seung Min (Department of Pharmacy, Severance Hospital, Yon-sei University Health System) ;
  • Ree, Yoon Sun (Department of Pharmacy, Severance Hospital, Yon-sei University Health System) ;
  • Kim, Jae Song (Department of Pharmacy, Severance Hospital, Yon-sei University Health System) ;
  • Kim, Soo Hyun (Department of Pharmacy, Severance Hospital, Yon-sei University Health System) ;
  • Son, Eun Sun (Department of Pharmacy, Severance Hospital, Yon-sei University Health System) ;
  • Lyu, Chuhl Joo (Department of Pediatric Hematology Oncology, Severance Hospital, Yon-sei University Health System)
  • 김승민 (연세대학교의료원 세브란스병원 약무국) ;
  • 이윤선 (연세대학교의료원 세브란스병원 약무국) ;
  • 김재송 (연세대학교의료원 세브란스병원 약무국) ;
  • 김수현 (연세대학교의료원 세브란스병원 약무국) ;
  • 손은선 (연세대학교의료원 세브란스병원 약무국) ;
  • 유철주 (연세대학교 세브란스병원 소아혈액종양과)
  • Received : 2018.02.20
  • Accepted : 2018.03.27
  • Published : 2018.09.03
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Abstract

Background: Posaconazole is a broad-spectrum triazole antifungal agent and the most recommended prophylactic antifungal agent for patients with acute myeloid leukemia (AML) undergoing induction chemotherapy. In this study, we evaluated the status and effectiveness of posaconazole as a prophylactic antifungal agent in pediatric patients receiving induction chemotherapy for AML. Methods: We retrospectively reviewed the electronic medical records of 36 pediatric patients with AML (between January 2013 and September 2017) at the Yonsei University Health System. Invasive fungal disease (IFD) was assessed as the primary endpoint of prophylactic antifungal effect. The secondary endpoints were incidence of fever, persistent fever despite the use of broad-spectrum antibiotics for 72 h, alteration of antifungal agent, intensive care unit admission, and death within 100 days. Results: Among the 36 patients, 18 patients used posaconazole, 12 were treated with suspension formula, and 6 of them were treated with tablets. Eighteen patients did not use antifungal agents prophylactically. The mean number of days of posaconazole administration was $26.8{\pm}16days$. IFD occurred in 2/18 (11.1%) patients in the no prophylaxis group and in 1/18 (5.6%) patients in the posaconazole group (p=0.49). Conclusion: Posaconazole is expected to be useful for the prevention of IFD in pediatric patients with AML undergoing induction chemotherapy. Prospective studies of the effectiveness of posaconazole prophylaxis should be conducted in more pediatric patients in the future.

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References

  1. Cuenca EM, Bernal ML, Buitrago MJ, et al. Update on the epidemiology and diagnosis of invasive fungal infection. Int J Antimicmb Agents 2008;32(2):143-7. https://doi.org/10.1016/S0924-8579(08)70016-5
  2. Berking S, Doedens D, Horns H, et al. Antifungal prophylaxis in newly diagnosed AML patients adherence to guidelines and feasibility in a real life setting. Mycoses 2017;60(9):600-6. https://doi.org/10.1111/myc.12635
  3. Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007;356(4):348-59. https://doi.org/10.1056/NEJMoa061094
  4. Jung DS, Tverdek FP, Kontoyiannis DP, et al. Switching from Posaconazole Suspension to Tablets Increases Serum Drug Levels in Leukemia Patients without Clinically Relevant Hepatotoxicity. Antimicrob Agents Chemother 2014;58(11):6993-5. https://doi.org/10.1128/AAC.04035-14
  5. Durani U, Tosh PK, Barreto JN, et al. Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension. Antimicrob Agents Chemother 2015; 59(8):4914-8. https://doi.org/10.1128/AAC.00496-15
  6. Bruggemann RJ, Alffenaar JW, Blijlevens NM, et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 2009;48(10):1441- 58. https://doi.org/10.1086/598327
  7. Krishna G, Moton A, Ma L, et al. Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 2009;53(3):958-66. https://doi.org/10.1128/AAC.01034-08
  8. Doring M, Muller C, Johann PD, et al. Analysis of Posaconazole as Oral Antifungal Prophylaxis in Pediatric Patients Under 12 Years of Age Following Allogeneic Stem Cell Transplantation. BMC Infect Dis 2012;12:263. https://doi.org/10.1186/1471-2334-12-263
  9. De PB, Walsh TJ, Donnelly JP, et al. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooper- ative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/ MSG) Consensus Group (2008) 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;46(12):1813-21. https://doi.org/10.1086/588660
  10. Lass-Florl C. The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 2009;52(3):197-205. https://doi.org/10.1111/j.1439-0507.2009.01691.x
  11. Kung HC, Kan LP, Lin HA, et al. Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology-oncology patients. Cancer Medicine 2014;3(3):667-73. https://doi.org/10.1002/cam4.225
  12. Cho SH, Lee DG, Choi SM, et al. Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single-centre retrospective study in Korea and clinical considerations. Mycoses 2015;58(9):565-71. https://doi.org/10.1111/myc.12357
  13. Pagano L, Stamouli M, Tumbarello M, et al. Risk of invasive fungal infection in patients affected by acute promyelocytic leukaemia. A report by the SEIFEM-D registry. Br J Haematol 2015;170(3):434-9. https://doi.org/10.1111/bjh.13308
  14. Muhlemann K, Wenger C, Zenhuusern R, et al. Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies. Leukemia 2005;19(4):545-50. https://doi.org/10.1038/sj.leu.2403674
  15. Doring M, Cabanillas KM, Queudeville M, et al. Efficacy, safety and feasibility of antifungal prophylaxis with posaconazole tablet in paediatric patients after haematopoietic stem cell transplantation. J Cancer Res Clin Oncol 2017;143(7):1281-92. https://doi.org/10.1007/s00432-017-2369-7
  16. Gwee A, Cranswick N, Cranswick N, et al. Posaconazole: Promising but Problematic in Practice in Pediatric Patients. The Pediatr Infect Dis J 2015;34(6):604-6. https://doi.org/10.1097/INF.0000000000000635
  17. Gross BN, Ihorst G, Jung M, et al. Posaconazole Therapeutic Drug Monitoring in the Real-life Setting. Pharmacotherapy 2013;33(10): 1117-25. https://doi.org/10.1002/phar.1328
  18. Doring M, Eikemeier M, Cabanillas KM, et al. Antifungal prophylaxis with posaconazole vs. fluconazole or itraconazole in pediatric patients with neutropenia. Eur J Clin Microbiol Infect Dis 2015;34(6):1189-200. https://doi.org/10.1007/s10096-015-2340-y