Randomized, Double‐Blind Clinical Trial of Amphotericin B Colloidal Dispersion vs. Amphotericin B in the Empirical Treatment of Fever and Neutropenia

Abstract

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Adverse effects of antifungal therapies in invasive fungal infections: review and meta-analysis

“…In the meta-analysis, 11 randomized controlled trials reported fever in patients receiving study medications: fluconazole vs AmB [17-19, 26, 32], L-AmB vs AmB [25,28], ABCD vs AmB [27,30], and ABLC vs L-AmB [31,34], but a majority of these studies were too heterogeneous to be pooled. With the exclusion of the German study by Abele-Horn et al [17], which used a dose of fluconazole inconsistent with the four other studies, trials comparing fluconazole with AmB had the following patient inclusion criteria: Malik et al [26] and Winston et al [32] required neutropenia [absolute neutrophil count (ANC) <500 cells/ mm 3 ]; Viscoli et al [18], Malik et al [26], and Winston et al [32] included only patients with hematologic malignancies and defined "fever" as >38°C, whereas Anaissie et al [19] used a threshold of >38.3°C (101°F).…”

“…Once pooled, there was no difference between the two antifungal agents causing rashes. Eight randomized trials reported bronchospasms, but only four used the same study drugs: fluconazole vs AmB [26,32] and ABCD vs AmB [27,30], where all included patients had hematologic malignancies or bone marrow transplants with neutropenia and 3 days of broad-spectrum antibiotics. The respiratory event profile was surprisingly more favorable for AmB than for ABCD.…”

Forum Report: Issues in Clinical Trials of Empirical Antifungal Therapy in Treating Febrile Neutropenic Patients

“…A study by Walsh et al [9] found liposomal amphotericin B to be comparable in efficacy but less toxic than amphotericin B deoxycholate. White et al [10] found amphotericin B colloidal dispersion to have comparable efficacy to but different toxicity than amphotericin B deoxycholate. Although amphotericin B lipid complex (Abelcet) has been compared with liposomal amphotericin B as empirical therapy in a randomized double-blind trial, the study was designed to compare safety and not efficacy [11].…”

Candidiasis invasoras en recién nacidos: diagnóstico, tratamiento y prevención

“…Un grupo de expertos de la Sociedad Europea de Microbiología Clínica e Infectología (ESCMID) se refiere al uso de L-amB, en dosis de 2,5 a 7 mg/kg/día en RN con un adecuado perfil de seguridad 38 . Los estudios con ABCL y ABDC son escasos 39,40 . No está recomendado el uso de formulaciones lipídicas de anfotericina B en caso de urocultivos positivos a Candida spp.…”