Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 4/2014

Open Access 01-04-2014 | Article

Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation

Authors: M. Döring, O. Blume, S. Haufe, U. Hartmann, A. Kimmig, C.-P. Schwarze, P. Lang, R. Handgretinger, I. Müller

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 4/2014

Login to get access

Abstract

Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents after high-dose chemotherapy and HSCT. Fifty consecutive pediatric patients received itraconazole, 50 received voriconazole, and 50 pediatric patients received posaconazole after HSCT as oral antifungal prophylaxis. The observation period lasted from the start of oral prophylactic treatment with itraconazole, voriconazole, or posaconazole until two weeks after terminating the oral antifungal prophylaxis. No incidences of proven or probable invasive mycosis were observed during itraconazole, voriconazole, or posaconazole treatment. A total of five possible invasive fungal infections occurred, two in the itraconazole group (4 %) and three in the voriconazole group (6 %). The percentage of patients with adverse events potentially related to clinical drugs were 14 % in the voriconazole group, 12 % in the itraconazole group, and 8 % in the posaconazole group. Itraconazole, voriconazole, and posaconazole showed comparable efficacy as antifungal prophylaxis in pediatric patients after allogeneic HSCT.
Literature
1.
3.
go back to reference Cuenca-Estrella M, Rodríguez-Tudela JL, Mellado E, Martínez-Suárez JV, Monzón A (1998) Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus. J Antimicrob Chemother 42:531–533PubMedCrossRef Cuenca-Estrella M, Rodríguez-Tudela JL, Mellado E, Martínez-Suárez JV, Monzón A (1998) Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus. J Antimicrob Chemother 42:531–533PubMedCrossRef
4.
go back to reference Espinel-Ingroff A, Canton E, Gibbs D, Wang A (2007) Correlation of Neo-Sensitabs tablet diffusion assay results on three different agar media with CLSI broth microdilution M27-A2 and disk diffusion M44-A results for testing susceptibilities of Candida spp. and Cryptococcus neoformans to amphotericin B, caspofungin, fluconazole, itraconazole, and voriconazole. J Clin Microbiol 45:858–864PubMedCentralPubMedCrossRef Espinel-Ingroff A, Canton E, Gibbs D, Wang A (2007) Correlation of Neo-Sensitabs tablet diffusion assay results on three different agar media with CLSI broth microdilution M27-A2 and disk diffusion M44-A results for testing susceptibilities of Candida spp. and Cryptococcus neoformans to amphotericin B, caspofungin, fluconazole, itraconazole, and voriconazole. J Clin Microbiol 45:858–864PubMedCentralPubMedCrossRef
5.
go back to reference Espinel-Ingroff A, Boyle K, Sheehan DJ (2001) In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia 150:101–115PubMedCrossRef Espinel-Ingroff A, Boyle K, Sheehan DJ (2001) In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia 150:101–115PubMedCrossRef
6.
go back to reference Potter M, Donnelly JP (2004) The role of itraconazole in preventing and treating systemic fungal infections in immunocompromised patients. Acta Haematol 111:175–180PubMedCrossRef Potter M, Donnelly JP (2004) The role of itraconazole in preventing and treating systemic fungal infections in immunocompromised patients. Acta Haematol 111:175–180PubMedCrossRef
7.
go back to reference Glasmacher A, Prentice A, Gorschlüter M, Engelhart S, Hahn C, Djulbegovic B et al (2003) Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol 21:4615–4626PubMedCrossRef Glasmacher A, Prentice A, Gorschlüter M, Engelhart S, Hahn C, Djulbegovic B et al (2003) Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol 21:4615–4626PubMedCrossRef
8.
go back to reference Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL et al (2003) Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med 138:705–713PubMedCrossRef Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL et al (2003) Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med 138:705–713PubMedCrossRef
9.
go back to reference Morgenstern GR, Prentice AG, Prentice HG, Ropner JE, Schey SA, Warnock DW (1999) A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haematol 105:901–911PubMedCrossRef Morgenstern GR, Prentice AG, Prentice HG, Ropner JE, Schey SA, Warnock DW (1999) A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haematol 105:901–911PubMedCrossRef
10.
go back to reference Vardakas KZ, Michalopoulos A, Falagas ME (2005) Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials. Br J Haematol 131:22–28PubMedCrossRef Vardakas KZ, Michalopoulos A, Falagas ME (2005) Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials. Br J Haematol 131:22–28PubMedCrossRef
11.
go back to reference Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW et al (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415PubMedCrossRef Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW et al (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415PubMedCrossRef
12.
go back to reference Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P et al (2002) Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J 21:240–248PubMedCrossRef Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P et al (2002) Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J 21:240–248PubMedCrossRef
13.
go back to reference Grigull L, Kuehlke O, Beilken A, Sander A, Linderkamp C, Schmid H et al (2007) Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric stem cell transplantation recipients: a pilot study for evaluation of safety and efficacy. Pediatr Transplant 11:261–266PubMedCrossRef Grigull L, Kuehlke O, Beilken A, Sander A, Linderkamp C, Schmid H et al (2007) Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric stem cell transplantation recipients: a pilot study for evaluation of safety and efficacy. Pediatr Transplant 11:261–266PubMedCrossRef
14.
go back to reference Cesaro S, Strugo L, Alaggio R, Cecchetto G, Rigobello L, Pillon M et al (2003) Voriconazole for invasive aspergillosis in oncohematological patients: a single-center pediatric experience. Support Care Cancer 11:722–727PubMedCrossRef Cesaro S, Strugo L, Alaggio R, Cecchetto G, Rigobello L, Pillon M et al (2003) Voriconazole for invasive aspergillosis in oncohematological patients: a single-center pediatric experience. Support Care Cancer 11:722–727PubMedCrossRef
15.
go back to reference Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G et al (2006) Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 50:126–133PubMedCentralPubMedCrossRef Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G et al (2006) Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 50:126–133PubMedCentralPubMedCrossRef
16.
go back to reference Maertens J, Groll AH, Cordonnier C, de la Cámara R, Roilides E, Marchetti O (2011) Treatment and timing in invasive mould disease. J Antimicrob Chemother 66:i37–i43PubMedCrossRef Maertens J, Groll AH, Cordonnier C, de la Cámara R, Roilides E, Marchetti O (2011) Treatment and timing in invasive mould disease. J Antimicrob Chemother 66:i37–i43PubMedCrossRef
17.
go back to reference Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G et al (2006) Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 42:1398–1403PubMedCrossRef Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G et al (2006) Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 42:1398–1403PubMedCrossRef
18.
go back to reference Raad II, Graybill JR, Bustamante AB, Cornely OA, Gaona-Flores V, Afif C et al (2006) Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis 42:1726–1734PubMedCrossRef Raad II, Graybill JR, Bustamante AB, Cornely OA, Gaona-Flores V, Afif C et al (2006) Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis 42:1726–1734PubMedCrossRef
19.
go back to reference Schering Corporation (2008) Prescribing information for Noxafil (posaconazole) oral suspension. Schering Corporation, Kenilworth, NJ Schering Corporation (2008) Prescribing information for Noxafil (posaconazole) oral suspension. Schering Corporation, Kenilworth, NJ
20.
go back to reference Krieter P, Flannery B, Musick T, Gohdes M, Martinho M, Courtney R (2004) Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob Agents Chemother 48:3543–3551PubMedCentralPubMedCrossRef Krieter P, Flannery B, Musick T, Gohdes M, Martinho M, Courtney R (2004) Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob Agents Chemother 48:3543–3551PubMedCentralPubMedCrossRef
21.
go back to reference Wexler D, Courtney R, Richards W, Banfield C, Lim J, Laughlin M (2004) Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci 21:645–653PubMedCrossRef Wexler D, Courtney R, Richards W, Banfield C, Lim J, Laughlin M (2004) Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci 21:645–653PubMedCrossRef
22.
go back to reference Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ et al (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356:348–359PubMedCrossRef Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ et al (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356:348–359PubMedCrossRef
23.
go back to reference Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR et al (2007) Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 356:335–347PubMedCrossRef Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR et al (2007) Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 356:335–347PubMedCrossRef
24.
go back to reference Döring M, Müller C, Johann PD, Erbacher A, Kimmig A, Schwarze CP et al (2012) Analysis of posaconazole as oral antifungal prophylaxis in pediatric patients under 12 years of age following allogeneic stem cell transplantation. BMC Infect Dis 12:263PubMedCentralPubMedCrossRef Döring M, Müller C, Johann PD, Erbacher A, Kimmig A, Schwarze CP et al (2012) Analysis of posaconazole as oral antifungal prophylaxis in pediatric patients under 12 years of age following allogeneic stem cell transplantation. BMC Infect Dis 12:263PubMedCentralPubMedCrossRef
25.
go back to reference de Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al (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 46:1813–1821PubMedCentralPubMedCrossRef de Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al (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 46:1813–1821PubMedCentralPubMedCrossRef
26.
go back to reference Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F et al (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34:7–14PubMedCrossRef Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F et al (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34:7–14PubMedCrossRef
28.
go back to reference Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P et al (2011) European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 update. Bone Marrow Transplant 46:709–718PubMedCrossRef Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P et al (2011) European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 update. Bone Marrow Transplant 46:709–718PubMedCrossRef
29.
go back to reference Cornely OA, Böhme A, Buchheidt D, Einsele H, Heinz WJ, Karthaus M et al (2009) Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 94:113–122PubMedCentralPubMedCrossRef Cornely OA, Böhme A, Buchheidt D, Einsele H, Heinz WJ, Karthaus M et al (2009) Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Haematologica 94:113–122PubMedCentralPubMedCrossRef
30.
go back to reference Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al (2009) Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15:1143–1238PubMedCentralPubMedCrossRef Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al (2009) Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15:1143–1238PubMedCentralPubMedCrossRef
31.
go back to reference Lehrnbecher T, Attarbaschi A, Duerken M, Garbino J, Gruhn B, Kontny U et al (2010) Posaconazole salvage treatment in paediatric patients: a multicentre survey. Eur J Clin Microbiol Infect Dis 29:1043–1045PubMedCrossRef Lehrnbecher T, Attarbaschi A, Duerken M, Garbino J, Gruhn B, Kontny U et al (2010) Posaconazole salvage treatment in paediatric patients: a multicentre survey. Eur J Clin Microbiol Infect Dis 29:1043–1045PubMedCrossRef
32.
go back to reference Cesaro S, Milano GM, Aversa F (2011) Retrospective survey on the off-label use of posaconazole in pediatric hematology patients. Eur J Clin Microbiol Infect Dis 30:595–596PubMedCrossRef Cesaro S, Milano GM, Aversa F (2011) Retrospective survey on the off-label use of posaconazole in pediatric hematology patients. Eur J Clin Microbiol Infect Dis 30:595–596PubMedCrossRef
33.
go back to reference Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191PubMedCrossRef Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191PubMedCrossRef
34.
go back to reference Winston DJ, Bartoni K, Territo MC, Schiller GJ (2011) Efficacy, safety, and breakthrough infections associated with standard long-term posaconazole antifungal prophylaxis in allogeneic stem cell transplantation recipients. Biol Blood Marrow Transplant 17:507–515PubMedCrossRef Winston DJ, Bartoni K, Territo MC, Schiller GJ (2011) Efficacy, safety, and breakthrough infections associated with standard long-term posaconazole antifungal prophylaxis in allogeneic stem cell transplantation recipients. Biol Blood Marrow Transplant 17:507–515PubMedCrossRef
36.
go back to reference Sánchez-Ortega I, Vázquez L, Montes C, Patiño B, Arnan M, Bermúdez A et al (2012) Effect of posaconazole on cyclosporine blood levels and dose adjustment in allogeneic blood and marrow transplant recipients. Antimicrob Agents Chemother 56:6422–6424. doi:10.1128/AAC.01489-12 PubMedCentralPubMedCrossRef Sánchez-Ortega I, Vázquez L, Montes C, Patiño B, Arnan M, Bermúdez A et al (2012) Effect of posaconazole on cyclosporine blood levels and dose adjustment in allogeneic blood and marrow transplant recipients. Antimicrob Agents Chemother 56:6422–6424. doi:10.​1128/​AAC.​01489-12 PubMedCentralPubMedCrossRef
38.
go back to reference Schmalreck AF, Willinger B, Haase G, Blum G, Lass-Flörl C, Fegeler W et al (2012) Species and susceptibility distribution of 1062 clinical yeast isolates to azoles, echinocandins, flucytosine and amphotericin B from a multi-centre study. Mycoses 55:e124–e137. doi:10.1111/j.1439-0507.2011.02165.x PubMedCrossRef Schmalreck AF, Willinger B, Haase G, Blum G, Lass-Flörl C, Fegeler W et al (2012) Species and susceptibility distribution of 1062 clinical yeast isolates to azoles, echinocandins, flucytosine and amphotericin B from a multi-centre study. Mycoses 55:e124–e137. doi:10.​1111/​j.​1439-0507.​2011.​02165.​x PubMedCrossRef
Metadata
Title
Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation
Authors
M. Döring
O. Blume
S. Haufe
U. Hartmann
A. Kimmig
C.-P. Schwarze
P. Lang
R. Handgretinger
I. Müller
Publication date
01-04-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 4/2014
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-013-1998-2

Other articles of this Issue 4/2014

European Journal of Clinical Microbiology & Infectious Diseases 4/2014 Go to the issue