Abstract
Voriconazole is increasingly used as a first-line agent for empirical antifungal therapy of prolonged febrile neutropenia in paediatric cancer patients. We describe the case of a 9-year-old patient with stage IV Burkitt lymphoma, who developed pulmonary and splenic zygomycosis while receiving voriconazole for persistent febrile neutropenia. The causative agent, Absidia corymbifera, was identified by broad-range fungal PCR in a lung biopsy sample. The patient was successfully treated with a combination of partial resection of the left upper lobe and antifungal therapy with high-dose liposomal amphotericin B followed by oral itraconazole as demonstrated by resolving pulmonary infiltrates on serial high resolution CT scans. Conclusion:This case emphasises that the lack of in vitro activity of voriconazole against zygomycetes is clinically relevant. Failure of voriconazole in suspected fungal infection should be investigated for the possibility of zygomycosis. Broad-range polymerase chain reaction may be able to identify the causative organism when cultures remain sterile.
Similar content being viewed by others
Abbreviations
- BAL :
-
bronchoalveolar lavage
- HRCT :
-
high-resolution computed tomography
- PET :
-
positron emission tomography
References
Bennett JE, Powers J, Walsh T, Viscoli C, de Pauw B, Dismukes W, Galgiani J, Glauser M, Herbrecht R, Kauffman C, Lee J, Pappas P, Rex J, Verweij P (2003) Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 36: S117–S122
Clement L, Salmon A, Mansuy L, Paczesny S, Bordigoni P (2004) Mucormycosis after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 33: S205
Dannaoui E, Meletiadis, Mouton JW, Meis JFGM, Verweij PE (2003) In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother 511: 45–52
Dannaoui E, Meis JF, Leobenberg D, Verweij PE (2003) Activity of posaconazole in treatment of experimental disseminated zygomycosis. Antimicrob Agent Chemother 47: 3647–3650
Gebhard F, Chastagner P, Maillot D, Kures L, Georges JL, Schmitt C, Bordigoni P, Sommelet D (1995) Evolution favorable d’une mucormycose orbitonasosinusienne compliquant le traitement d’induction d’une leucémie aiguë lymphoblastique. Arch Pédiatr 2: 47–51
Grigull L, Beier R, Schrauder, Kirschner P, Loening L, Jack T, Welte K, Sykora KW, Schrappe M (2003) Invasive fungal infections are responsible for one-fifth of infectious death in children with ALL. Mycoses 46: 441–446
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 34: 730–751
Johnson EM, Szekely A, Warnock DW (1998) In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi. J Antimicrob Chemother 42: 741–745
Leong KW, Crowley B, White B, Crotty GM, O’Brian DS, Keane C, McCann SR (1997) Cutaneous mucormycosis due to Absidia corymbifera occurring after bone marrow transplantation. Bone Marrow Transplant 19: 513–515
Marty FM, Cosimi LA, Baden LR (2004) Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 350: 950–951
Parkyn T, McNinch AW, Riordan T, Mott M (2000) Zygomycosis in relapsed acute leukaemia. J Infect 41: 265–282
Rickerts V, Loeffler J, Böhme A, Einsele H, Just-Nübling G (2001) Diagnosis of disseminated zygomycosis using a polymerase chain reaction assay. Eur J Clin Microbiol Infect Dis 20: 744–745
Ryan M, Yeo S, Maguire A, Webb D, O’Marcaigh A, McDermott M, Butler K, O’Meara A (2001) Rhinocerebral zygomycosis in childhood acute lymphoblastic leukaemia. Eur J Pediatr 160: 235–238
Tobon AM, Arango M, Fernandez D, Restrepo A (2003) Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis 36: 1488–1491
Wali YA, Al Lamki Z, Al Kindi H, Taqi AM, Shah W, Soliman H, Zackaria M, Al Okbi H (2001) Successful outcome of invasive nasal sinus zygomycosis in a child with relapsed acute lymphoblastic leukaemia due to liposomal amphotericin B. Mycoses 44: 195–199
Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, Hodges M, Groll AH, Perfect JR (2002) Voriconazole in treatment of aspergillosis, scedosporosis and other invasive fungal infections in children. Pediatr Infect Dis J 21: 240–248
Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J (2002) Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 346: 225–234
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ritz, N., Ammann, R.A., Aebischer, C.C. et al. Failure of voriconazole to cure disseminated zygomycosis in an immunocompromised child. Eur J Pediatr 164, 231–235 (2005). https://doi.org/10.1007/s00431-004-1606-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-004-1606-7