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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis

Authors: Ken Chen, Qi Wang, Roy A. Pleasants, Long Ge, Wei Liu, Kangning Peng, Suodi Zhai

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

The most optimal antifungal agent for empiric treatment of invasive fungal diseases (IFDs) in febrile neutropenia is controversial. Our objective was evaluate the relative efficacy of antifungals for all-cause mortality, fungal infection-related mortality and treatment response in this population.

Methods

Pubmed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs). Two reviewers performed the quality assessment and extracted data independently. Pairwise meta-analysis and network meta-analysis were conducted to compare the antifungals.

Results

Seventeen RCTs involving 4583 patients were included. Risk of bias of included studies was moderate. Pairwise meta-analysis indicated the treatment response rate of itraconazole was significantly better than conventional amphotericin B (RR = 1.33, 95%CI 1.10–1.61). Network meta-analysis showed that amphotericin B lipid complex, conventional amphotericin B, liposomal amphotericin B, itraconazole and voriconazole had a significantly lower rate of fungal infection-related mortality than no antifungal treatment. Other differences in outcomes among antifungals were not statistically significant. From the rank probability plot, caspofungin appeared to be the most effective agent for all-cause mortality and fungal infection-related mortality, whereas micafungin tended to be superior for treatment response. The results were stable after excluding RCTs with high risk of bias, whereas micafungin had the lowest fungal infection-related mortality.

Conclusions

Our results highlighted the necessity of empiric antifungal treatment and indicates that echinocandins appeared to be the most effective agents for empiric treatment of febrile neutropenic patients based on mortality and treatment response. However, more studies are needed to determine the best antifungal agent for empiric treatment. Our systematic review has been prospectively registered in PROSPERO and the registration number was CRD42015026629.
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Literature
1.
Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91(7):986–9.PubMed
2.
Slobbe L, Polinder S, Doorduijn JK, Lugtenburg PJ, el Barzouhi A, Steyerberg EW, et al. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clin Infect Dis. 2008;47(12):1507–12.CrossRefPubMed
3.
Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis. 2009;48(3):265–73.CrossRefPubMed
4.
Bitar D, Lortholary O, Le SY, Nicolau J, Coignard B, Tattevin P, et al. Population-based analysis of invasive fungal infections, France, 2001–2010. Emerg Infect Dis. 2014;20(7):1149–55.CrossRefPubMed
5.
Pagano L, Caira M, Candoni A, Offidani M, Martino B, Specchia G, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica. 2010;95(4):644–50.CrossRefPubMed
6.
Pagano L, Caira M, Picardi M, Candoni A, Melillo L, Fianchi L, et al. Invasive Aspergillosis in patients with acute leukemia: update on morbidity and mortality--SEIFEM-C Report. Clin Infect Dis. 2007;44(11):1524–5.CrossRefPubMed
7.
Singh N. Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin Infect Dis. 2001;33(10):1692–6.CrossRefPubMed
8.
De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. 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.CrossRefPubMedPubMedCentral
9.
Schmiedel Y, Zimmerli S. Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia. Swiss Med Wkly. 2016;146:w14281.PubMed
10.
Goldberg E, Gafter-Gvili A, Robenshtok E, Leibovici L, Paul M. Empirical antifungal therapy for patients with neutropenia and persistent fever: systematic review and meta-analysis. Eur J Cancer. 2008;44(15):2192–203.CrossRefPubMed
11.
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;62(4):e1–50.CrossRefPubMed
12.
Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63:e1-60.
13.
Maertens J, Marchetti O, Herbrecht R, Cornely OA, Flückiger U, Frêre P, et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3–2009 update. Bone Marrow Transplant. 2011;46(5):709–18.CrossRefPubMed
14.
15.
Ge L, Tian JH, Li L, Wang Q, Yang KH. Mesh fixation methods in open inguinal hernia repair: a protocol for network meta-analysis and trial sequential analysis of randomised controlled trials. BMJ Open. 2015;5(11):e009369.CrossRefPubMedPubMedCentral
16.
Gelman A, Rubin DB. Inference from iterative simulation using multiple sequences. Stat Sci. 1992;7:457–72.CrossRef
17.
Boogaerts M, Winston DJ, Bow EJ, Garber G, Reboli AC, Schwarer AP, et al. Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med. 2001;135(6):412–22.CrossRefPubMed
18.
Caselli D, Cesaro S, Ziino O, Ragusa P, Pontillo A, Pegoraro A, et al. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children. Br J Haematol. 2012;158(2):249–55.CrossRefPubMed
19.
Groll AH, Silling G, Young C, Schwerdtfeger R, Ostermann H, Heinz WJ, et al. Randomized comparison of safety and pharmacokinetics of caspofungin, liposomal amphotericin B, and the combination of both in allogeneic hematopoietic stem cell recipients. Antimicrob Agents Chemother. 2010;54(10):4143–9.CrossRefPubMedPubMedCentral
20.
Jadhav M, PShinde VM, Chandrakala S, Jijina F, Menon H, Arora B, et al. A randomized comparative trial evaluating the safety and efficacy of liposomal amphotericin B (Fungisome) versus conventional amphotericin B in the empirical treatment of febrile neutropenia in India. Indian J Cancer. 2012;49(1):107–13.CrossRefPubMed
21.
Maertens JA, Madero L, Reilly AF, Lehrnbecher T, Groll AH, Jafri HS, et al. A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin B for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. Pediatr infect dis j. 2010;29(5):415–20.CrossRefPubMed
22.
Meunier F. Empirical antifungal therapy in febrile granulocytopenic patients. Am j med. 1989;86(6 I):668–72.
23.
Oyake T, Kowata S, Murai K, Ito S, Akagi T, Kubo K, et al. Comparison of micafungin and voriconazole as empirical antifungal therapies in febrile neutropenic patients with hematological disorders: a randomized controlled trial. Eur J Haematol. 2016;96(6):602–9.CrossRefPubMed
24.
Prentice HG, Hann IM, Herbrecht R, Aoun M, Kvaloy S, Catovsky D, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997;98(3):711–8.CrossRefPubMed
25.
Schiel X, Link H, Maschmeyer G, Glass B, Cornely OA, Buchheidt D, et al. A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich society for chemotherapy (PEG) multicenter trial II. Infection. 2006;34(3):118–26.CrossRefPubMed
26.
Schuler U, Bammer S, Aulitzky WE, Binder C, Böhme A, Egerer G, et al. Safety and efficacy of itraconazole compared to amphotericin B as empirical antifungal therapy for neutropenic fever in patients with haematological malignancy. Onkologie. 2007;30(4):185–91.PubMed
27.
Viscoli C, Castagnola E, Van Lint MT, Moroni C, Garaventa A, Rossi MR, et al. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer. 1996;32A(5):814–20.CrossRefPubMed
28.
Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, et al. Liposomal amphotericin b for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999;340(10):764–71.CrossRefPubMed
29.
Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002;346(4):225–34.CrossRefPubMed
30.
Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351(14):1391–402.CrossRefPubMed
31.
Wang J, Sun AN, Wu DP, Chen SN, Qiu HY, Jin ZM, et al. Comparison of caspofungin and liposomal amphotericin B for empirical antifungal therapy in patients with hematologic disease. Chin J Antibiot. 2007;32(5):316.
32.
Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. Clin Infect Dis. 2000;31(5):1155–63.CrossRefPubMed
33.
Jeong SH, Kim DY, Jang JH, Mun YC, Choi CW, Kim SH, et al. Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study. Ann Hematol. 2016;95(2):337–44.CrossRefPubMed
34.
Blyth CC, Hale K, Palasanthiran P, O’Brien T, Bennett MH. Antifungal therapy in infants and children with proven, probable or suspected invasive fungal infections. Cochrane Database Syst Rev. 2010;2:CD006343.
35.
Blyth CC, Palasanthiran P, O’Brien TA. Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics. 2007;119(4):772–84.CrossRefPubMed
36.
Zhang J, Gong Y, Wang K, Kong J, Chen Y. Caspofungin versus liposomal amphotericin B for treatment of invasive fungal infections or febrile neutropenia. Chin Med J (Engl). 2014;127(4):753–7.
37.
Freemantle N, Tharmanathan P, Herbrecht R. Systematic review and mixed treatment comparison of randomized evidence for empirical, pre-emptive and directed treatment strategies for invasive mould disease. J Antimicrob Chemother. 2011;66 Suppl 1:i25–35.CrossRefPubMed
38.
Pound MW, Townsend ML, Drew RH. Echinocandin pharmacodynamics: review and clinical implications. J Antimicrob Chemother. 2010;65(6):1108–18.CrossRefPubMed
39.
Nett JE, Andes DR. Antifungal agents: spectrum of activity, pharmacology, and clinical indications. Infect Dis Clin North Am. 2016;30(1):51–83.CrossRefPubMed
40.
Kohno S, Izumikawa K, Yoshida M, Takesue Y, Oka S, Kamei K, et al. A double-blind comparative study of the safety and efficacy of caspofungin versus micafungin in the treatment of candidiasis and aspergillosis. Eur J Clin Microbiol Infect Dis. 2013;32(3):387–97.CrossRefPubMed
41.
Stam WB, Aversa F, Kumar RN, Jansen JP. Economic evaluation of caspofungin versus liposomal amphotericin B for empiric antifungal treatment in patients with neutropenic fever in Italy. Value Health. 2008;11(5):830–41.CrossRefPubMed
42.
Al-Badriyeh D, Liew D, Stewart K, Kong DC. Economic impact of caspofungin as compared with liposomal amphotericin B for empirical therapy in febrile neutropenia in Australia. J Antimicrob Chemother. 2009;63(6):1276–85.CrossRefPubMed
43.
Naik S, Lundberg J, Kumar R, Sjolin J, Jansen JP. Economic evaluation of caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia in Sweden. Scand J Infect Dis. 2011;43(6–7):504–14.CrossRefPubMed
44.
Al-Badriyeh D, Liew D, Stewart K, Kong DC. Pharmacoeconomic analysis of voriconazole vs. caspofungin in the empirical antifungal therapy of febrile neutropenia in Australia. Mycoses. 2012;55(3):244–56.CrossRefPubMed
45.
Turner SJ, Senol E, Kara A, Al-Badriyeh D, Dinleyici EC, Kong DC. Cost effectiveness of caspofungin vs. voriconazole for empiric therapy in Turkey. Mycoses. 2014;57(8):489–96.CrossRefPubMed
Metadata
Title
Empiric treatment against invasive fungal diseases in febrile neutropenic patients: a systematic review and network meta-analysis
Authors
Ken Chen
Qi Wang
Roy A. Pleasants
Long Ge
Wei Liu
Kangning Peng
Suodi Zhai
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2263-6

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