Skip to main content
Top
Published in: Supportive Care in Cancer 9/2016

Open Access 01-09-2016 | Original Article

Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry

Authors: Roberta Della Pepa, M. Picardi, F. Sorà, M. Stamouli, A. Busca, A. Candoni, M. Delia, R. Fanci, V. Perriello, M. Zancanella, A. Nosari, P. Salutari, F. Marchesi, F. Pane, L. Pagano, on behalf of the SEIFEM group (Sorveglianza Epidemiologica Infezioni Fungine in Ematologia)

Published in: Supportive Care in Cancer | Issue 9/2016

Login to get access

Abstract

Purpose

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC.

Methods

In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated.

Results

Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6—100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned.

Conclusions

This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.
Literature
1.
go back to reference Beck-Sague C, Jarvis WR (1993) Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. National Nosocomial Infections Surveillance System. J Infect Dis 167(5):1247–1251CrossRefPubMed Beck-Sague C, Jarvis WR (1993) Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. National Nosocomial Infections Surveillance System. J Infect Dis 167(5):1247–1251CrossRefPubMed
2.
go back to reference Jarvis WR, Martone WJ, Suppl A (1992) Predominant pathogens in hospital infections. J Antimicrob Chemother 29:19–24CrossRefPubMed Jarvis WR, Martone WJ, Suppl A (1992) Predominant pathogens in hospital infections. J Antimicrob Chemother 29:19–24CrossRefPubMed
3.
go back to reference Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, Pastore D, Picardi M, Bonini A, Chierichini A, Fanci R, Caramatti C, Invernizzi R, Mattei D, Mitra ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C, Nosari A (2006) The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91(8):1068–1075PubMed Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, Pastore D, Picardi M, Bonini A, Chierichini A, Fanci R, Caramatti C, Invernizzi R, Mattei D, Mitra ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C, Nosari A (2006) The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91(8):1068–1075PubMed
4.
go back to reference Pagano L, Caira M, Rossi G, Tumbarello M, Fanci R, Garzia MG, Vianelli N, Filardi N, De Fabritiis P, Beltrame A, Musso M, Piccin A, Cuneo A, Cattaneo C, Aloisi T, Riva M, Rossi G, Salvadori U, Brugiatelli M, Sannicolo S, Morselli M, Bonini A, Viale P, Nosari A, Aversa F, Hema e-Chart Group I (2012) A prospective survey of febrile events in hematological malignancies. Ann Hematol 91(5):767–774. doi:10.1007/s00277-011-1373-2 CrossRefPubMed Pagano L, Caira M, Rossi G, Tumbarello M, Fanci R, Garzia MG, Vianelli N, Filardi N, De Fabritiis P, Beltrame A, Musso M, Piccin A, Cuneo A, Cattaneo C, Aloisi T, Riva M, Rossi G, Salvadori U, Brugiatelli M, Sannicolo S, Morselli M, Bonini A, Viale P, Nosari A, Aversa F, Hema e-Chart Group I (2012) A prospective survey of febrile events in hematological malignancies. Ann Hematol 91(5):767–774. doi:10.​1007/​s00277-011-1373-2 CrossRefPubMed
6.
go back to reference Lewis RE, Cahyame-Zuniga L, Leventakos K, Chamilos G, Ben-Ami R, Tamboli P, Tarrand J, Bodey GP, Luna M, Kontoyiannis DP (2013) Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study. Mycoses 56(6):638–645. doi:10.1111/myc.12081 CrossRefPubMed Lewis RE, Cahyame-Zuniga L, Leventakos K, Chamilos G, Ben-Ami R, Tamboli P, Tarrand J, Bodey GP, Luna M, Kontoyiannis DP (2013) Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study. Mycoses 56(6):638–645. doi:10.​1111/​myc.​12081 CrossRefPubMed
7.
go back to reference Jarvis WR (1995) Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 20(6):1526–1530CrossRefPubMed Jarvis WR (1995) Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 20(6):1526–1530CrossRefPubMed
8.
go back to reference Perduca M, Marangoni E, Guanziroli A, Romero E, Filice G (1995) Fungaemia in hospitalized patients. Mycoses 38(9–10):385–387CrossRefPubMed Perduca M, Marangoni E, Guanziroli A, Romero E, Filice G (1995) Fungaemia in hospitalized patients. Mycoses 38(9–10):385–387CrossRefPubMed
9.
go back to reference Nosari AM, Caira M, Pioltelli ML, Fanci R, Bonini A, Cattaneo C, Castagnola C, Capalbo SF, De Fabritiis P, Mettivier V, Morselli M, Pastore D, Aversa F, Rossi G, Pagano L, Hema e-Chart Group I (2013) Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections. Clin Microbiol Infect 19(8):757–762. doi:10.1111/1469-0691.12014 CrossRefPubMed Nosari AM, Caira M, Pioltelli ML, Fanci R, Bonini A, Cattaneo C, Castagnola C, Capalbo SF, De Fabritiis P, Mettivier V, Morselli M, Pastore D, Aversa F, Rossi G, Pagano L, Hema e-Chart Group I (2013) Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections. Clin Microbiol Infect 19(8):757–762. doi:10.​1111/​1469-0691.​12014 CrossRefPubMed
11.
go back to reference 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, Munoz 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 R, Treatment of Cancer/Invasive Fungal Infections Cooperative G, National Institute of A, Infectious Diseases Mycoses Study Group Consensus G (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(12):1813–1821. doi:10.1086/588660 CrossRefPubMedPubMedCentral 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, Munoz 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 R, Treatment of Cancer/Invasive Fungal Infections Cooperative G, National Institute of A, Infectious Diseases Mycoses Study Group Consensus G (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(12):1813–1821. doi:10.​1086/​588660 CrossRefPubMedPubMedCentral
12.
go back to reference 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 (2008) 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 47(5):674–683. doi:10.1086/590566 CrossRefPubMedPubMedCentral 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 (2008) 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 47(5):674–683. doi:10.​1086/​590566 CrossRefPubMedPubMedCentral
13.
go back to reference Kaplan ELM, P (1958) Nonparametric estimation from incomplete observations. J Amer Statist Assn 53:457–481CrossRef Kaplan ELM, P (1958) Nonparametric estimation from incomplete observations. J Amer Statist Assn 53:457–481CrossRef
14.
go back to reference Kaplan EL (1983) This week’s citation classic. Current Contents 24:14 Kaplan EL (1983) This week’s citation classic. Current Contents 24:14
15.
go back to reference Blade J, Lopez-Guillermo A, Rozman C, Granena A, Bruguera M, Bordas J, Cervantes F, Carreras E, Sierra J, Montserrat E (1992) Chronic systemic candidiasis in acute leukemia. Ann Hematol 64(5):240–244CrossRefPubMed Blade J, Lopez-Guillermo A, Rozman C, Granena A, Bruguera M, Bordas J, Cervantes F, Carreras E, Sierra J, Montserrat E (1992) Chronic systemic candidiasis in acute leukemia. Ann Hematol 64(5):240–244CrossRefPubMed
16.
go back to reference Pagano L, Mele L, Fianchi L, Melillo L, Martino B, D’Antonio D, Tosti ME, Posteraro B, Sanguinetti M, Trape G, Equitani F, Carotenuto M, Leone G (2002) Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes. Haematologica 87(5):535–541PubMed Pagano L, Mele L, Fianchi L, Melillo L, Martino B, D’Antonio D, Tosti ME, Posteraro B, Sanguinetti M, Trape G, Equitani F, Carotenuto M, Leone G (2002) Chronic disseminated candidiasis in patients with hematologic malignancies. Clinical features and outcome of 29 episodes. Haematologica 87(5):535–541PubMed
17.
go back to reference Ellis M, Frampton C, Joseph J, Alizadeh H, Kristensen J, Hauggaard A, Shammas F (2006) An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy. J Med Microbiol 55(Pt 10):1357–1365. doi:10.1099/jmm.0.46452-0 CrossRefPubMed Ellis M, Frampton C, Joseph J, Alizadeh H, Kristensen J, Hauggaard A, Shammas F (2006) An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy. J Med Microbiol 55(Pt 10):1357–1365. doi:10.​1099/​jmm.​0.​46452-0 CrossRefPubMed
19.
go back to reference Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of A (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48(5):503–535. doi:10.1086/596757 CrossRefPubMed Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of A (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48(5):503–535. doi:10.​1086/​596757 CrossRefPubMed
21.
go back to reference Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S, Bille J, Castagnola E, Cuenca-Estrella M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Florl C, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ, Group EFIS (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37. doi:10.1111/1469-0691.12039 CrossRefPubMed Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S, Bille J, Castagnola E, Cuenca-Estrella M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Florl C, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ, Group EFIS (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 18(Suppl 7):19–37. doi:10.​1111/​1469-0691.​12039 CrossRefPubMed
22.
go back to reference Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely OA, Egerer G, Kruger W, Link H, Neumann S, Ostermann H, Panse J, Penack O, Rieger C, Schmidt-Hieber M, Silling G, Sudhoff T, Ullmann AJ, Wolf HH, Maschmeyer G, Bohme A (2014) Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 93(1):13–32. doi:10.1007/s00277-013-1867-1 CrossRefPubMed Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely OA, Egerer G, Kruger W, Link H, Neumann S, Ostermann H, Panse J, Penack O, Rieger C, Schmidt-Hieber M, Silling G, Sudhoff T, Ullmann AJ, Wolf HH, Maschmeyer G, Bohme A (2014) Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 93(1):13–32. doi:10.​1007/​s00277-013-1867-1 CrossRefPubMed
23.
go back to reference Cornely OA, Maertens J, Bresnik M, Ebrahimi R, Ullmann AJ, Bouza E, Heussel CP, Lortholary O, Rieger C, Boehme A, Aoun M, Horst HA, Thiebaut A, Ruhnke M, Reichert D, Vianelli N, Krause SW, Olavarria E, Herbrecht R, AmBiLoad Trial Study G (2007) Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 44(10):1289–1297. doi:10.1086/514341 CrossRefPubMed Cornely OA, Maertens J, Bresnik M, Ebrahimi R, Ullmann AJ, Bouza E, Heussel CP, Lortholary O, Rieger C, Boehme A, Aoun M, Horst HA, Thiebaut A, Ruhnke M, Reichert D, Vianelli N, Krause SW, Olavarria E, Herbrecht R, AmBiLoad Trial Study G (2007) Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 44(10):1289–1297. doi:10.​1086/​514341 CrossRefPubMed
25.
go back to reference Ellis M, Spence D, de Pauw B, Meunier F, Marinus A, Collette L, Sylvester R, Meis J, Boogaerts M, Selleslag D, Krcmery V, von Sinner W, MacDonald P, Doyen C, Vandercam B (1998) An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis. Clin Infect Dis 27(6):1406–1412CrossRefPubMed Ellis M, Spence D, de Pauw B, Meunier F, Marinus A, Collette L, Sylvester R, Meis J, Boogaerts M, Selleslag D, Krcmery V, von Sinner W, MacDonald P, Doyen C, Vandercam B (1998) An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis. Clin Infect Dis 27(6):1406–1412CrossRefPubMed
26.
go back to reference Vogelsinger H, Weiler S, Djanani A, Kountchev J, Bellmann-Weiler R, Wiedermann CJ, Bellmann R (2006) Amphotericin B tissue distribution in autopsy material after treatment with liposomal amphotericin B and amphotericin B colloidal dispersion. J Antimicrob Chemother 57(6):1153–1160. doi:10.1093/jac/dkl141 CrossRefPubMed Vogelsinger H, Weiler S, Djanani A, Kountchev J, Bellmann-Weiler R, Wiedermann CJ, Bellmann R (2006) Amphotericin B tissue distribution in autopsy material after treatment with liposomal amphotericin B and amphotericin B colloidal dispersion. J Antimicrob Chemother 57(6):1153–1160. doi:10.​1093/​jac/​dkl141 CrossRefPubMed
Metadata
Title
Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry
Authors
Roberta Della Pepa
M. Picardi
F. Sorà
M. Stamouli
A. Busca
A. Candoni
M. Delia
R. Fanci
V. Perriello
M. Zancanella
A. Nosari
P. Salutari
F. Marchesi
F. Pane
L. Pagano
on behalf of the SEIFEM group (Sorveglianza Epidemiologica Infezioni Fungine in Ematologia)
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 9/2016
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-016-3208-0

Other articles of this Issue 9/2016

Supportive Care in Cancer 9/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine