Efficacy and tolerance of an amphotericm B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients

Abstract

The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients.

Comparison of the Activity of Free and Liposomal Amphotericin B In Vitro and in a Model of Systemic and Localized Murine Candidiasis

“…Attempts have been made to lower AmB toxicity by entrapping it in liposomes [4][5][6][7][8], complexing it with lipids [9][10][11][12], or administering Amls-desoxycholate (AmB-d) in a lipid emulsion [13][14][15][16]. However, it is the potential of AmB to preferentially bind to ergosterol rather than to cholesterol that is the key to understanding its fungicidal and toxic activity [17][18][19].…”

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

“…In fact, several clinical trials reveal the efficacy of such strategy 2,4,12 . However, additional studies should be addressed to this "new pharmaceutical entity" to clearly understand its mechanism of action.…”

“…in the first one, AmB-D was previously reconstituted with distilled water for injection and then, added to the parenteral emulsion (AmB-DAL) (9-11). The second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL) (12 M, respectively) were used for the in vitro profile of activity or toxicity. To evaluate the effectiveness and toxicity of AmB, 4mL of RBC (5 x 10 7 cell/ml) or 2mL of Ct (5 x 10 7 cfu/ml) suspension were incubated by one hour at 37ºC with AmB-D, AmB-DL or AmB-DAL, respectively.…”

Efficacy of amphotericin B in a fat emulsion for the treatment of cryptococcal meningitis in AIDS patients

“…Thus, an alternative system based on AmB in the fat emulsion intralipid (AmB-IL), clinically used for parenteral nutrition, has given a reduction in the adverse effects during administration and the nephrotoxicity of AmB in neutropenic and critically ill patients, as well as providing a good therapeutic efficacy [10][11][12][13][14].…”