Antifungal prophylaxis among allogeneic hematopoietic stem cell transplant recipients: current issues and new agents

Strasfeld, Lynne; Weinstock, David M.

doi:10.1586/14787210.4.3.457

Cited by 15 publications

(9 citation statements)

References 65 publications

(22 reference statements)

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“…2,4 For practical purposes, the risk group of infections after HSCT can be divided with respect to the type of transplantation as: (a) low risk: autologous HSCT; (b) moderate risk: matched sibling donor HSCT with no GVHD (myeloablative, low-toxicity and reduced-intensity conditioning); (c) high risk: unrelated, mismatched, haploidentical, cord blood HSCT, T-cell depletion or CD34 selection, patients with moderate-to-severe GVHD and CMV infection. Multivariate analysis has identified the use of steroids as the most significant variable associated with infectious episodes.…”

Section: Risk Factors Of Infectionsmentioning

confidence: 99%

Prevention of infectious complications in pediatric HSCT

Styczyński

Gil

2008

Bone Marrow Transplant

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Infectious complications constitute a major cause of morbidity and mortality in pediatric and adult patients undergoing hematopoietic SCT (HSCT). Current guidelines and recommendations for prevention of infections in children after HSCT are presented in this mini review. The paper is based on evidence-based recommendations rated by the strength of the recommendation and the quality of the supporting evidence. Prophylaxis strategy based on risk stratification includes: (1) general infection control in hospital environment, (2) pharmacological approach related to antibacterial, antifungal and antiviral agents and (3) vaccination. Although most studies were carried out on adults only, some included both pediatric and adult patients. No differences in prophylaxis strategy and efficacy among age groups are reported. With changing practices, transplant teams are encouraged to review local patterns of prophylaxis strategy.

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Section: Risk Factors Of Infectionsmentioning

confidence: 99%

Prevention of infectious complications in pediatric HSCT

Styczyński

Gil

2008

Bone Marrow Transplant

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“…Once IFI has occurred in patients who have received immunosuppressants for prophylaxis or treatment of acute graft-versus-host disease (GVHD), the prognosis is very poor. The incidence of IFI in patients who have undergone allogeneic SCT is higher than that in those who have undergone autologous SCT [1]. For this indication, fluconazole (FLCZ) has been routinely used in many institutions and has shown excellent antifungal effects in both patients who have undergone autologous SCT and allogeneic SCT [2,3].…”

Section: Introductionmentioning

confidence: 99%

Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation

et al. 2007

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Objective: Invasive fungal infection is one of the major causes of death in neutropenic patients undergoing allogeneic stem cell transplantation (SCT). Although prophylactic antifungal therapy with fluconazole (FLCZ) has become the standard care for these patients, there remains a need for more effective and cost-beneficial alternative drugs.Patients and Methods: We conducted a prospective study to evaluate the usefulness of the administration of micafungin (MCFG) as a prophylactic antifungal therapy for patients undergoing allogeneic SCT. The results were compared with previous data for patients who had received FLCZ.Results: A total of 44 patients who underwent allogeneic SCT were enrolled in the study.Data from 29 patients who received allogeneic SCT using prophylactic FLCZ before this study were used as historical control data. Underlying diseases included acute leukemia (n=16), non-Hodgkin's lymphoma (n=11), myelodysplastic syndrome (n=6), and others (n=11) in the MCFG group and acute leukemia (n=18), chronic myelogenous leukemia (n=6), and others (n=5) in the FLCZ group. The median durations of administration of MCFG and FLCZ were 36 and 34 days, respectively. Prophylactic success, defined as the absence of proven, probable, and possible invasive fungal infection (IFI) until the end of prophylactic therapy was achieved in 36 (87.8%) of the 41 evaluated patients in the MCFG group and in 65.5% of the patients in the FLCZ group (p=0.038). No patients in the MCFG group showed proven or probable IFI, whereas proven or probable IFI was observed in 3 patients in the FLCZ group. Four patients in the MCFG group required dose escalation due to febrile neutropenia. Although one patient in the MCFG group required the discontinuation of MCFG due to allergic skin eruption (grade 2), none of the other patients in either group required dose reduction due to adverse effects.Conclusions: Although the study design was not a prospective randomized trial, our results indicate that the administration of MCFG at a daily dose of 100 mg is promising for prophylactic antifungal therapy in patients undergoing allogeneic SCT.

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“…Treatment of an established IFI is frequently very difficult, and the most effective agents have treatmentlimiting toxicities (19). Consequently, antifungal prophylaxis is increasingly being used for patients at high risk of acquiring a fungal infection; the benefits of antifungal prophylaxis include reduced mortality as well as reduced health care costs (5,6,10,12,17,18,20). However, there are concerns that the prophylactic agent may select for less susceptible isolates.…”

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confidence: 99%

Impact of Antifungal Prophylaxis on Colonization and Azole Susceptibility of Candida Species

Mann¹,

McNicholas²,

Chau³

et al. 2009

Antimicrob Agents Chemother

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Two large studies compared posaconazole and fluconazole or itraconazole for prophylaxis in subjects undergoing allogeneic hematopoietic stem cell transplantation or subjects with acute myelogenous leukemia. To assess the impact of prophylaxis on colonization and the development of resistance in Saccharomyces yeasts, identification and susceptibility testing were performed with yeasts cultured at regular intervals from mouth, throat, and stool samples. Prior to therapy, 34 to 50% of the subjects were colonized with yeasts. For all three drugs, the number of positive Candida albicans cultures decreased during drug therapy. In contrast, the proportion of subjects with positive C. glabrata cultures increased by two-and fourfold in the posaconazole and itraconazole arms, respectively. Likewise, in the fluconazole arm the proportion of subjects with positive C. krusei cultures increased twofold. C. glabrata was the species that most frequently exhibited decreases in susceptibility, and this trend did not differ significantly between the prophylactic regimens. For the subset of subjects from whom colonizing C. glabrata isolates were recovered at the baseline and the end of treatment, approximately 40% of the isolates exhibited more than fourfold increases in MICs during therapy. Molecular typing of the C. albicans and C. glabrata isolates confirmed that the majority of the baseline and end-of-treatment isolates were closely related, suggesting that they were persistent colonizers and not newly acquired. Overall breakthrough infections by Candida species were very rare (ϳ1%), and C. glabrata was the colonizing species that was the most frequently associated with breakthrough infections.Invasive fungal infections (IFIs) are a leading cause of morbidity and mortality in neutropenic patients with hematological malignancies and recipients of hematopoietic stem cell transplants (HSCT). Treatment of an established IFI is frequently very difficult, and the most effective agents have treatmentlimiting toxicities (19). Consequently, antifungal prophylaxis is increasingly being used for patients at high risk of acquiring a fungal infection; the benefits of antifungal prophylaxis include reduced mortality as well as reduced health care costs (5,6,10,12,17,18,20). However, there are concerns that the prophylactic agent may select for less susceptible isolates. Changes in susceptibility can be caused by mutations in existing colonizing isolates, through overgrowth (by a previously minor species), or by de novo colonization by inherently less susceptible species. This concern is particularly relevant for Candida, since colonization of the oral mucosa, gastrointestinal tract, and skin are risk factors associated with the acquisition of invasive Candida infections (11, 13).Two large randomized clinical trials compared orally administered posaconazole with either fluconazole or itraconazole for antifungal prophylaxis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) or HSCT recipients receiving high-dose im...

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Antifungal prophylaxis among allogeneic hematopoietic stem cell transplant recipients: current issues and new agents

Cited by 15 publications

References 65 publications

Prevention of infectious complications in pediatric HSCT

Prevention of infectious complications in pediatric HSCT

Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation

Impact of Antifungal Prophylaxis on Colonization and Azole Susceptibility of Candida Species

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