Empirical antifungal therapy for patients with neutropenia and persistent fever: Systematic review and meta-analysis

2008 ◽  
Vol 44 (15) ◽  
pp. 2192-2203 ◽  
Author(s):  
Elad Goldberg ◽  
Anat Gafter-Gvili ◽  
Eyal Robenshtok ◽  
Leonard Leibovici ◽  
Mical Paul
Keyword(s):  
Systematic Review ◽  
Antifungal Therapy ◽  
Meta Analysis ◽  
Persistent Fever ◽  
Empirical Antifungal Therapy

Empirical Antifungal Therapy for Patients with Neutropenia and Persitent Fever - Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4961-4961
Author(s):  
Elad Goldberg ◽  
Anat Gafter-Gvili ◽  
Mical Paul ◽  
Eyal Robenshtok ◽  
Liat Vidal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Fungal Infections ◽  
Meta Analysis ◽  
Persistent Fever ◽  
All Cause Mortality ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients

Abstract Background: Opportunistic invasive fungal infections (IFIs) are a major concern in the management of immunocompromised patients with hematological malignancies. The practice of administering antifungal therapy to neutropenic patients with persistent fever has become a standard care. Conflicting data exists concerning the efficacy of empirical antifungal therapy. Objectives: This study aims to evaluate if empirical antifungal therapy reduces mortality and prevents invasive fungal infections (IFI). Methods: Systematic review and meta-analysis including randomized controlled trials (RCTs) comparing empirical antifungal treatment with placebo or no intervention (control), or another regimen, in neutropenic patients with persistent fever. The Cochrane Library, MEDLINE, conference proceedings and references were searched until 2007. Outcomes assessed were: All-cause mortality, documented IFI, and adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Results: Our search yielded 26 trials, 6 of which compared polyenes or azoles to control, and 20 compared between different regimens of polyenes, azoles or glucan synthesis inhibitors. Compared to control, there was no difference in all-cause mortality (RR 0.98; 95% CI 0.58–1.66, 5 trials, Fig.1). The risk for developing documented IFI was lower (RR 0.23; 95% CI 0.08–0.65, 4 trials, 4 events in the treatment group versus 18 in the control). When azoles (fluconazole, ketoconazole, itraconazole, voriconazole) were compared to polyenes (amphotericin B in 8 trials, liposomal ampho B in 1 trial) there was a trend in favor of azoles for decreased all-cause mortality (RR 0.89; 95% CI 0.73–1.09, 9 trials) and for decreased documented IFI (RR 0.70; 95% CI 0.47–1.04, 8 trials). Adverse events of any kind were less frequent in the azole group (RR 0.40; 95% CI 0.34–0.66, 5 trials), as were those which required discontinuation (RR 0.48; 95% CI 0.38–0.62, 7 trials). Conclusions: Our review demonstrates that empirical antifungal therapy does not reduce mortality. Although it reduces IFIs, data are based on a small number of trials and events. The use of amphotericin B as empirical antifungal therapy seems unwarranted since it appears to be less effective than azoles, with no mortality benefit and an increased rate of side effects. Future trials should pursue a pre-emptive approach using improved diagnostic tools (such as galactomannan testing, high resolution CT), to identify the patients for whom antifungal treatment is warranted. Figure Figure

P963 Empirical antifungal therapy in febrile neutropenic patients-systematic review

2007 ◽  
Vol 29 ◽  
pp. S253-S254
Author(s):  
E. Goldberg ◽  
A. Gafter-Gvili ◽  
M. Paul ◽  
E. Robenshtok ◽  
L. Vidal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antifungal Therapy ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients

scholarly journals Systematic Review and Meta-Analysis of the Tolerability and Hepatotoxicity of Antifungals in Empirical and Definitive Therapy for Invasive Fungal Infection

2010 ◽  
Vol 54 (6) ◽  
pp. 2409-2419 ◽  
Author(s):  
Jiun-Ling Wang ◽  
Chia-Hsuin Chang ◽  
Yinong Young-Xu ◽  
K. Arnold Chan
Keyword(s):  
Systematic Review ◽  
Liver Injury ◽  
Fungal Infection ◽  
Liver Enzyme ◽  
Antifungal Therapy ◽  
Invasive Fungal Infection ◽  
Adverse Reactions ◽  
Meta Analysis ◽  
Elevated Serum ◽  
Treatment Discontinuation

ABSTRACT To evaluate the tolerability and liver safety profiles of the systemic antifungal agents commonly used for the treatment of invasive fungal infection, we conducted a systematic review and meta-analysis of randomized controlled trials published before 31 August 2009. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. We used the beta-binomial model to account for variation across studies and the maximum likelihood method to estimate the pooled risks. We identified 39 studies with more than 8,000 enrolled patients for planned comparisons. The incidence rates of treatment discontinuation due to adverse reactions and liver injury associated with antifungal therapy ranged widely. The pooled risks of treatment discontinuation due to adverse reactions were above 10% for amphotericin B formulations and itraconazole, whereas they were 2.5% to 3.8% for fluconazole, caspofungin, and micafungin. We found that 1.5% of the patients stopped itraconazole treatment due to hepatotoxicity. Furthermore, 19.7% of voriconazole users and 17.4% of itraconazole users had elevated serum liver enzyme levels, although they did not require treatment discontinuation, whereas 2.0% or 9.3% of fluconazole and echinocandin users had elevated serum liver enzyme levels but did not require treatment discontinuation. The results were similar when we stratified the data by empirical or definitive antifungal therapy. Possible explanations for antifungal agent-related hepatotoxicity were confounded by antifungal prescription to patients with a high risk of liver injury, the increased chance of detection of hepatotoxicity due to prolonged treatment, or the pharmacological entity.

Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Persistent Fever and Neutropenia

2004 ◽  
Vol 351 (14) ◽  
pp. 1391-1402 ◽  
Author(s):  
Thomas J. Walsh ◽  
Hedy Teppler ◽  
Gerald R. Donowitz ◽  
Johan A. Maertens ◽  
Lindsey R. Baden ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
Persistent Fever ◽  
Empirical Antifungal Therapy

Efficacy and Safety of Micafungin as An Empirical Antifungal Therapy for Suspected Fungal Infection in Patients with Hematological Disorders.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1939-1939
Author(s):  
Minoru Yoshida ◽  
Kazuo Tamura ◽  
Masahiro Imamura ◽  
Yoshiro Niitsu ◽  
Takeshi Sasaki ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Antifungal Therapy ◽  
Clinical Symptoms ◽  
Fungal Infections ◽  
Efficacy And Safety ◽  
Hematopoietic Stem ◽  
Persistent Fever ◽  
Hematological Disorders ◽  
Study Results ◽  
Empirical Antifungal Therapy

Abstract Background: Invasive fungal infections (IFIs) are of serious concern in the management of immunocompromised patients (pts) with hematological disorders. Empiric antifungal therapy is recommended for neutropenic pts with persistent fever, because treatment after confirmation of fungal infection often produces poor outcomes. Micafungin (MCFG), one of the echinocandin families, was launched first in Japan in 2002, and has now been approved in more than 11 countries and areas including the USA and the EU. Although the efficacy and safety of MCFG against both Candida and Aspergillus infections has been shown in many clinical trials, there are few clinical study reports on the empiric therapy of a suspected fungal infection. Here, we report the multi-center study results of MCFG for the empiric antifungal therapy, which were conducted from April 2005 to September 2006 in Japan. Objective: This prospective study was performed to clarify the efficacy and safety of MCFG for the empirical antifungal therapy on suspected fungal infection in pts with hematological disorders and neutropenia. Methods: Study design: A multiple-center, open, uncontrolled study. The investigator registered pts with neutropenia (< 1,000/μl) who met the following criteria to the Subject Registration Center. Suspected fungal infections were divided into two categories: possible fungal infection defined by positive clinical symptoms/findings and serological testing (beta-D-glucan or galactomannan) or diagnostic imaging (chest X-ray or CT scan), refractory fever defined by unexplained persistent fever (an axillary temperature higher than 37.5 °C) after the antibacterial treatment over 2 days and by positive clinical symptoms/findings. IFIs categorized as proven or probable were not included in this study. Efficacy evaluation was performed using an algorithm based on each of the evaluation of clinical symptoms/findings, imaging study findings, and serological tests. Results: 388 pts (M:234, F:154, mean age:57.8 years old) were registered. The mean dosage and duration of treatment with MCFG were 154.6±55.3 mg/day and 14.0±6.9 days, respectively. The main underlying hematological disorders were acute leukemia (61.3%), non-Hodgkin’s lymphoma (18.3%) and myelodysplastic syndrome (10.8%). The number of pts with hematopoietic stem cell transplantation (HSCT) was 76 (19.6%). The clinical response rate (CRR), excluding 4 non-evaluable pts was 63.3% (243/384): 60.1% (89/148) for pts with possible fungal infection and 65.3% (154/236) for pts with refractory fever, respectively. Even in persistent neutropenic pts whose neutrophil counts were < 500/μL throughout the treatment with MCFG, the CRR was high enough: 46.9% (61/130). No difference was observed in the CRR among the main underlying hematological disorders. The CRR in pts with HSCT and other conditions were 63.2% (48/76) and 63.3% (195/308), respectively. Drug-related adverse events (DAEs) were observed in 16.8% (65/388). Serious DAEs such as elevation of serum bilirubin and renal dysfunction was observed in 0.52% (2/388). Conclusion: MCFG was confirmed to have high clinical efficacy and be safe for the treatment of suspected fungal infection in pts with hematological disorders and neutropenia.

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