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

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

scholarly journals Safety, Tolerance, and Pharmacokinetics of a Small Unilamellar Liposomal Formulation of Amphotericin B (AmBisome) in Neutropenic Patients

1998 ◽  
Vol 42 (9) ◽  
pp. 2391-2398 ◽  
Author(s):  
Thomas J. Walsh ◽  
Vijay Yeldandi ◽  
Maureen McEvoy ◽  
Corina Gonzalez ◽  
Stephen Chanock ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
High Performance ◽  
Fungal Infections ◽  
Empirical Therapy ◽  
Liposomal Formulation ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients

ABSTRACT The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.

Liposomal Amphotericin B (L-AMB) Is Superior to Amphotericin B Deoxycholate (AmB-d) in Preventing Breakthrough Fungal Infections in Patients with Prolonged Neutropenia and Fever: Results of a Sub-Group Analysis of an Empirical Antifungal Therapy Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1336-1336
Author(s):  
Catherine Cordonnier ◽  
Thomas J. Walsh ◽  
Mark Bresnik
Keyword(s):  
Treatment Group ◽  
Antifungal Therapy ◽  
Median Duration ◽  
Fungal Infections ◽  
Clinical Success ◽  
Group Analysis ◽  
Candida Spp ◽  
All Cause Mortality ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients

Abstract In a trial of empirical antifungal therapy in persistently febrile neutropenic patients, L-AMB was shown to be comparable in overall efficacy with significantly less nephrotoxicity and infusion-related reactions when compared to AmB-d. In addition, significantly fewer proven breakthrough invasive fungal infections (IFI) occurred in the L-AMB treatment group. (Walsh TJ, et al, NEJM1999; 340: 764–71). In order to better evaluate the maximum efficacy benefit of L-AMB in a higher risk patient subset, a sub-group analysis was performed on those patients with duration of neutropenia greater than or equal to the median duration for the entire study population. The results of this sub-group analysis are presented. Methods: From the original data set, the median duration of neutropenia from the time of treatment initiation was determined. Clinical success (defined by a composite endpoint), frequency of proven breakthrough IFI and all cause mortality were reported by treatment group for patients with duration of neutropenia greater than or equal to the median. Investigator-reported proven breakthrough IFI were reviewed and verified by an independent, blinded expert. Results: A total of 687 patients were enrolled in the trial. Median duration of neutropenia following initiation of antifungal therapy was 7 days (range 1–50). 392 patients had neutropenia >/= 7 days, (L-AMB=205), (AmB-d=187). Clinical success: L-AMB: 128/205 (62.4%); AmB-d: 112/187 (59.9%), and all cause mortality: L-AMB: 19/205 (9.3%); AmB-d: 24/187 (12.8%) were not significantly different. The frequency of proven breakthrough IFI favored L-AMB: L-AMB: 7/205 (3.4%); AmB-d: 18/187 (9.6%), p=0.01. Organisms isolated: L-AMB: 2 Candida spp (blood); 4 Aspergillus spp. (3 pneumonia, 1 wound); 1 Mucor sp (pneumonia). AmB-d: 9 Candida spp (8 blood, 1 pneumonia); 7 Aspergillus spp (4 pneumonia, 1 sinus, 1 pericarditis, 1 wound); 1 Cryptococcus albidus (blood); 1 unclassified mould (pneumonia). The difference in emergent proven IFI for the patients with neutropenia <7d trended in favor of L-AMB, but was not statistically significant: L-AMB 3/138 (2.2%); AmB-d 8/157 (5.1%). Conclusions: Overall clinical success and all cause mortality remained equivalent for the 2 treatment arms in the subset of patients with prolonged neutropenia. However, L-AMB significantly reduced the frequency of proven breakthrough IFI in this high-risk patient population. These data support the efficacy of L-AMB as empirical therapy, particularly for persistently neutropenic patients at higher risk for invasive fungal infections.

EP.WE.14Prognostic significance of metabolic syndrome in patients undergoing carotid artery revascularisation: A systematic review and meta-analysis

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh
Keyword(s):  
Myocardial Infarction ◽  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Long Term Outcomes ◽  
Short Term ◽  
All Cause Mortality ◽  
Major Adverse Events

Abstract Aims to evaluate prognostic significance of metabolic syndrome (MetS) in patients undergoing carotid artery revascularisation. Methods A systematic review and meta-analysis was performed in compliance with PRISMA standards to evaluate prognostic significance of MetS in patients undergoing carotid endarterectomy or carotid stenting. Short-term (&lt;30 days) postoperative outcomes (all-cause mortality, stroke or transient ischaemic attack (TIA), myocardial infarction, major adverse events) and long-term outcomes (restenosis, all-cause mortality, stroke or TIA, myocardial infarction, major adverse events) were considered as outcomes of interest. Random effects modelling was applied for the analyses. Results Analysis of 3721 patients from five cohort studies showed no difference between the MetS and no MetS groups in terms of the following short-term outcomes: all-cause mortality (OR: 1.67,P=0.32), stroke or TIA (OR: 2.44,P=0.06), myocardial infarction (OR: 1.01,P=0.96), major adverse events (OR: 1.23, P = 0.66). In terms of long-term outcomes, MetS was associated with higher risk of restenosis (OR: 1.75,P=0.02), myocardial infarction (OR: 2.12,P=0.04), and major adverse events (OR: 1.30, P = 0.009) but there was no difference between the two groups in terms of all-cause mortality (OR: 1.11, P = 0.25), and stroke or TIA (OR: 1.24, P = 0.33). The quality and certainty of the available evidence were judged to be moderate. Conclusions The best available evidence suggest that although MetS may not affect the short-term postoperative morbidity and mortality outcomes in patients undergoing carotid revascularisation, it may result in higher risks of restenosis, myocardial infarction and major adverse events in the long-term. Evidence from large prospective cohort studies are required for more robust conclusions.

Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis

2007 ◽  
Vol 25 (34) ◽  
pp. 5471-5489 ◽  
Author(s):  
Eyal Robenshtok ◽  
Anat Gafter-Gvili ◽  
Elad Goldberg ◽  
Miriam Weinberger ◽  
Moshe Yeshurun ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem ◽  
All Cause Mortality ◽  
Related Mortality

Purpose To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions. Methods We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data. Results Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole. Conclusion Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.

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

Immunoglobulin Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation - Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4962-4962
Author(s):  
Pia Raanani ◽  
Anat Gafter-Gvili ◽  
Mical Paul ◽  
Isaac Ben-Bassat ◽  
Leonard Leibovici ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Adverse Events ◽  
Acute Gvhd ◽  
Meta Analysis ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
All Cause Mortality ◽  
Autologous Hsct

Abstract Background: Many studies have evaluated the role of polyvalent immunoglobulins (IVIG) and CMV-hyperimmune IVIG (CMV-IVIG) prophylaxis in patients undergoing hematopoietic stem cell transplantation (HSCT), with inconsistent results and implications for practice. Objectives: To evaluate the role of IVIG and CMV- IVIG prophylaxis in HSCT. Methods: Systematic review and meta-analysis of randomized controlled trials comparing IVIG or CMV- IVIG with placebo or no intervention (control) for prophylaxis in HSCT. The Cochrane Library, MEDLINE, conference proceedings and references were searched until 2007. Primary outcome: all-cause-mortality ; Secondary outcomes: CMV infections, acute graft versus host disease (GVHD), interstitial pneumonitis (IP), veno-occlusive disease (VOD) and adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Results: Nineteen trials met inclusion criteria. IVIG was compared to control in 10 trials (7 IVIG in allogeneic HSCT, 2 allogeneic/autologous HSCT and 1 autologous HSCT). When IVIG was compared to control, there was no difference in all-cause mortality (RR 1.03; 95% CI 0.89–1.18, 6 trials, Fig.). There was a reduction in the number of CMV infections (RR 0.70; 95% CI 0.50–0.99, 4 trials) and in the number of episodes of IP (RR 0.61; 95% CI 0.43–0.87, 6 trials). There was no significant difference in the number of episodes of acute GVHD (RR 0.93; 95% CI 0.83–1.05, 6 trials). The risk for VOD was increased (RR 2.71; 95% CI 1.06–6.94, 3 trials) as were adverse events in the IVIG group (RR 8.12; 95% CI 3.15–20.9, 5 trials). CMV-IVIG was compared to control in 7 trials, all allogeneic HSCT. There was no difference in all-cause mortality (RR 0.86; 95% CI 0.63–1.16, 4 trials). In addition, there were no differences in the risk for developing CMV infections (RR 1.07; 95% CI 0.86–1.33, 7 trials), acute GVHD (RR 1.02; 95% CI 0.72–1.44, 5 trials) or IP (0.95; 95% CI 0.58–1.56, 5 trials). Conclusions: Our review demonstrates that IVIG prophylaxis for HSCT reduces the risk for CMV infections and IP without a significant influence on mortality. The beneficial effects should be weighed against the higher incidence of adverse events, VOD, and cost associated with the use of prophylactic IVIG in HSCT patients. Conversely, the use of CMV-IVIG was not associated with a change in any of the parameters. Outcomes Summary Outcome IVIG vs. control CMV-IVIG vs. control All Cause Mortality RR 1.03; 95% CI 0.89–1.18 RR 0.86; 95% CI 0.63–1.16 CMV infections RR 0.70; 95% CI 0.50–0.99 RR 1.07; 95% CI 0.86–1.33 acute GVHD RR 0.93; 95% CI 0.83–1.05 RR 1.02; 95% CI 0.72–1.44 IP RR 0.61; 95% CI 0.43–0.87 RR 0.95; 95% CI 0.58–1.56 VOD RR 2.71; 95% CI 1.06–6.94 No data Adverse events RR 8.12; 95% CI 3.15–20.9 RR 7.0; 95% CI 0.38–129.34 Figure Figure

Micafungin Versus Voriconazole for Empirical Antifungal Therapy In Febrile Neutropenic Patients with Acute Myeloid Leukemia: A Randomized, Controlled Trial.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1062-1062
Author(s):  
Tatsuo Oyake ◽  
Shugo Kowata ◽  
Kazunori Murai ◽  
Shigeki Ito ◽  
Tomoaki Akagi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Antifungal Therapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Controlled Trial ◽  
End Point ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients ◽  
Acute Myeloid

Abstract Abstract 1062 Background: Invasive fungal infections (IFIs) incur significant morbidity and mortality among neutropenic patients after chemotherapy. The risk for these infections is related to the intensity and duration of neutropenia, and varies from 2% to 40%. Mortality rates associated with documented IFIs are considerable, reportedly ranging from 30% to 60%. Empirical antifungal therapy is the standard care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Several antifungal agents including voriconazole (VRCZ) or liposomal amphotericin B (L-AMB) have been studied as empirical therapy for febrile neutropenia (FN). However, limited data are available concerning the efficacy of micafungin (MCFG) in FN patients with acute myeloid leukemia (AML). Methods: We conducted a randomized, cooperative group, open-label trial comparing MCFG (150 mg once daily) with VRCZ (6 mg/kg twice on day 1 followed by 4 mg/kg twice daily) as first-line empirical antifungal treatment for 95 hospitalized FN patients with AML during induction or consolidation chemotherapy (MCFG, 49; VRCZ, 46). The efficacy end point was a favorable overall response, as determined by a five-component end point according to the criteria of Walsh et al (N Engl J Med 2004; 351: 1391). Results: At the time of enrolment, there were no significant differences in the demographics or baseline characteristics between the two groups. The mean treatment duration for MCFG and VRCZ was 10 and 9 days, respectively. The efficacy rates of MCFG and VRCZ were not significantly different (37.8% vs. 32.4%). The rates of breakthrough fungal infections (proven, probable and possible IFIs), successful treatment of baseline fungal infections, survival 7 days after end of therapy, and resolution of fever during neutropenia were similar in the two groups. However, premature discontinuation of therapy occurred less often in the MCFG group than in the VRCZ group (32.4% vs. 55.9%, P=0.0457*). In safety evaluation, there were fewer adverse events in the MCFG group than in the VRCZ group (27.0% vs. 64.7%, P=0.0013*). *: Chi square test Conclusions: MCFG was as effective as VRCZ, and better tolerated than VRCZ as empirical antifungal therapy in FN patients with AML. Disclosures: No relevant conflicts of interest to declare.

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