Abstract
Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.
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Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, Nosari A, Buelli M, Picardi M, Allione B, Corvatta L, D’Antonio D, Montillo M, Melillo L, Chierichini A, Cenacchi A, Tonso A, Cudillo L, Candoni A, Savignano C, Bonini A, Martino P, Del Favero A. GIMEMA Infection Program; Gruppo Italiano Malattie Ematologiche dell’Adulto. Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program. Haematologica. 2001;86(8):862–70.
Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34(7):909–17.
Patterson JE. Epidemiology of fungal infections in solid organ transplant patients. Transpl Infect Dis. 1999;1(4):229–36.
Kriengkauykiat J, Ito JI, Dadwal SS. Epidemiology and treatment approaches in management of invasive fungal infections. Clin Epidemiol. 2011;3:175–91.
Shoham S. Emerging fungal infections in solid organ transplant recipients. Infect Dis Clin North Am. 2013;27(2):305–16.
Mullane K, Toor AA, Kalnicky C, Rodriguez T, Klein J, Stiff P. Posaconazole salvage therapy allows successful allogeneic hematopoietic stem cell transplantation in patients with refractory invasive mold infections. Transpl Infect Dis. 2007;9(2):89–96.
Vigouroux S, Morin O, Moreau P, Méchinaud F, Morineau N, Mahé B, Chevallier P, Guillaume T, Dubruille V, Harousseau JL, Milpied N. Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required. Clin Infect Dis. 2005;40(4):e35–7.
Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, Safdar A, Kantarjian H, Champlin R, Walsh TJ, Raad II. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191(8):1350–60.
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.
Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, Dromer F, Desenclos JC, Lortholary O. Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006. Emerg Infect Dis. 2009;15(9):1395–401.
Sabatelli F, Patel R, Mann PA, Mendrick CA, Norris CC, Hare R, Loebenberg D, Black TA, McNicholas PM. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006;50(6):2009–15.
Heinz WJ, Egerer G, Lellek H, Boehme A, Greiner J. Posaconazole after previous antifungal therapy with voriconazole for therapy of invasive aspergillus disease, a retrospective analysis. Mycoses. 2013;56(3):304–10.
Huang X, Wang F, Chen Y, Liu T, Wang J, Hu J, Jie J, Chen F, Wang S, Shen Z, Yu L, Yu K, Liang Y. A multicenter, open-label study of posaconazole oral suspension in the treatment of invasive fungal infections in patients refractory to or intolerant of first-line therapy. Future Microbiol. 2012;7(2):201–9.
Alexander BD, Perfect JR, Daly JS, Restrepo A, Tobón AM, Patino H, Hardalo CJ, Graybill JR. Posaconazole as salvage therapy in patients with invasive fungal infections after solid organ transplant. Transplantation. 2008;86(6):791–6.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 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.
Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, Walsh TJ, Maertens J, Patterson TF, Perfect JR, Dupont B, Wingard JR, Calandra T, Kauffman CA, Graybill JR, Baden LR, Pappas PG, Bennett JE, Kontoyiannis DP, Cordonnier C, Viviani MA, Bille J, Almyroudis NG, Wheat LJ, Graninger W, Bow EJ, Holland SM, Kullberg BJ, Dismukes WE, De Pauw BE. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008;47(5):674–83.
Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Langston A, Louie A, Ribaud P, Segal BH, Stevens DA, van Burik JA, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Perfect JR. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44(1):2–12.
Raad II, Hanna HA, Boktour M, Jiang Y, Torres HA, Afif C, Kontoyiannis DP, Hachem RY. Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin. Leukemia. 2008;22(3):496–503.
van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42(7):e61–5.
Lee HJ, Kwon JC, Kim SH, Choi SM, Lee DG, Park SH, Choi JH, Yoo JH, Cho BS, Lee S, Kim HJ, Min CK, Lee JW, Min WS. Posaconazole treatment in Korea: single-center experience over 5 years. Yonsei Med J. 2013;54(5):1234–40.
Dolton MJ, Ray JE, Chen SC, Ng K, Pont L, McLachlan AJ. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration. Antimicrob Agents Chemother. 2012;56(11):5503–10.
Kontoyiannis DP, Lewis RE. How I treat mucormycosis. Blood. 2011;118(5):1216–24.
Raad II, Graybill JR, Bustamante AB, Cornely OA, Gaona-Flores V, Afif C, Graham DR, Greenberg RN, Hadley S, Langston A, Negroni R, Perfect JR, Pitisuttithum P, Restrepo A, Schiller G, Pedicone L, Ullmann AJ. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis. 2006;42(12):1726–34.
Acknowlegments
This work was supported by an investigator initiated grant from Merck to JH Kim (MISP 50495).
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J.H. Kim has received research funding from Merck.
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Kim, J.H., Williams, K. Posaconazole Salvage Treatment for Invasive Fungal Infection. Mycopathologia 178, 259–265 (2014). https://doi.org/10.1007/s11046-014-9792-y
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DOI: https://doi.org/10.1007/s11046-014-9792-y