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

2001 ◽  
Vol 135 (6) ◽  
pp. 412 ◽  
Author(s):  
Marc Boogaerts
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Broad Spectrum ◽  
Persistent Fever ◽  
Patients With Cancer ◽  
Amphotericin B Deoxycholate ◽  
Oral Itraconazole ◽  
Empirical Antifungal Therapy ◽  
Neutropenic Patients ◽  
Intravenous Amphotericin

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

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

Safety and Efficacy of Caspofungin as Preventive and Empirical Antifungal Treatment of Neutropenic Allografted Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5024-5024
Author(s):  
Patrice Chevallier ◽  
Pierre Bordigoni ◽  
Thierry Lamy ◽  
Philippe Moreau ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Therapy ◽  
Antibacterial Therapy ◽  
Conditioning Regimen ◽  
Antifungal Treatment ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
Who Grade ◽  
Persistent Fever ◽  
Neutropenic Patients

Abstract Antifungal therapy is appropriate in neutropenic patients who have unexplained persistent fever, despite receipt of few days of antibacterial therapy. Conventional or liposomal amphotericin B are the preferred agents in this situation for allografted patients but toxicity or interaction with other drugs could limit their prescription. Caspofungin, the first inhibitor of fungal cell wall glucan synthesis, is the only echinocandin approved by the FDA for treatment of candidiasis. In case of suspected or documented aspergillosis infection, caspofungin is generally reserved to patients who failed to respond to amphotericin B or voriconazole. Recently, Walsh et al (ICAAC 2003) demonstrated in a randomised trial that caspofungin was comparable to liposomal amphotericine B in overall success as empirical antifungal therapy of persistently febrile neutropenic patients and was better tolerated. Here, we report our experience of caspofungin as preventive and empirical anti-fungal treatment, between November 2002 and May 2003, in 19 allografted patients with neutropenia (< 500/mm3 neutrophils) ± persistent fever despite at least 4 days of appropriate antibacterial therapy (n=12). There were 15 adult and 4 children, 11 male and 8 female. Median age was 33 years (range: 3–57). There were 6 ALL, 5 AML, 1 Myelodysplasia, 1 CML, 1 Hodgkin disease, 1 NHL, 1 myeloma, 1 aplastic anemia, 1 carcinoma and 1 Ewing sarcoma. A myeloablative conditioning regimen was used in 14 patients consisting of total body irradiation (TBI) plus high-dose chemotherapy in 9 patients and busulfan plus cyclophosphamide in 5 patients. A non myeloablative conditioning regimen was used in 5 patients. For graft-versus-host disease prophylaxis, the regimen was cyclosporin plus methotrexate in 13 patients or ATG in 6 patients. Nine patients received a bone marrow graft, 9 received granulocyte-colony-stimulating factor (G-CSF) mobilized peripheral blood stem-cells and 1 received an unrelated cord blood transplant. Twelve/19 patients have received prophylaxis with fluconazole from day 0 of the graft. Patients received caspofungin at an initial dose of 70 mg then 50 mg per day. Caspofungin was initiated within a median of 10 days after allograft (range: 0–174) including 7 patients receiving preventive caspofungin treatment at the date of aplasia. The mean duration of caspofungin therapy was 16 days (range: 3–72). Caspofungin was well tolerated and not stopped because of toxicity: WHO grade 1 and 2 hepatotoxicity occurred in 5 patients including 3 with previous hepatic abnormalities, WHO grade 1 and 2 nephrotoxicity occurred in 6 patients. No infusion reaction was observed. Only one patient developed a probable invasive bronchopulmonary aspergillosis on day 30 while receiving caspofungin. Seventeen/19 (89%) patients remain alive at least 7 days after the end of caspofungin administration without documented or suspected fungal, bacterial, or viral infection. Resolution of fever occurred in 11/12 febrile neutropenic patients in a median of 2 days (range:2–13) after starting caspofungin. We conclude that caspofungin is safe and effective as preventive and empirical antifungal treatment of neutropenic allografted patients.

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.

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