Cost-Effectiveness Analysis of Caspofungin Compared to Conventional Amphotericin B (C-AMB) for Empirical Antifungal Therapy in Febrile Neutropenic Patients in Thailand

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

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PIN16 COST-EFFECTIVENESS ANALYSIS OF MICAFUNGIN VERSUS LIPOSOMAL AMPHOTERICIN B IN THE TREATMENT OF PAEDIATRIC PATIENTS WITH SYSTEMIC CANDIDA INFECTIONS

Value in Health ◽

10.1016/s1098-3015(10)72923-5 ◽

2010 ◽

Vol 13 (3) ◽

pp. A189

Author(s):

A Odeyemi ◽

WM Hart ◽

II Odeyemi ◽

P Musingarimi

Keyword(s):

Cost Effectiveness ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Cost Effectiveness Analysis ◽

Liposomal Amphotericin B ◽

Effectiveness Analysis ◽

Paediatric Patients ◽

Candida Infections

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2391 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2391-2398 ◽

Cited By ~ 128

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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