Amphotericin B

Lipid formulations of amphotericin B, including liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion, have improved safety profiles compared to amphotericin B deoxycholate. Lower rates of infusion related reactions and nephrotoxicity are observed with these agents. However, while these toxicities are reduced they are not eliminated (21-23). Furthermore, the extent to which these formulations have improved outcomes is unclear. Most available efficacy data for the lipid formulations for the treatment of invasive aspergillosis come from small, open-label studies that have enrolled heterogeneous patient populations (Fig. 1). Only amphotericin B colloidal dispersion has been compared directly to amphotericin B deoxycholate with no differences in response rates (51% and 52%, respectively) reported in a randomized double-blind study (24). The other lipid formulations have been compared to amphotericin B deoxycholate against invasive fungal infections not limited to those caused by Aspergillus species. In one study involving 55 patients with document or suspected invasive aspergillosis, a trend in favor of liposomal amphotercin B compared to amphotericin B deoxycholate was reported (25). However, the number of patients with documented infection was small and the difference in response rates did not reach significance.

Despite the availability and extensive use of lipid formulations for the treatment of invasive fungal infections the optimal dose of these agents still remains in question. Standard doses in clinical trials have ranged between 3 and 5mg/kg/day. Higher doses (up to 10mg/kg/day) have been advocated for the treatment of fungal infections involving the central nervous system

Figure 1 Response rates to antifungal therapy from (A) open-label studies and (B) randomized controlled trials. Abbreviations: ABCD, amphotericin B colloidal dispersion; ABLC, amphotercin B lipid complex; CAS, caspofungin; ITZ, itraconazole; LAMB, liposomal amphotericin B; MFG, micafungin; VOR, voriconazole.

Figure 1 Response rates to antifungal therapy from (A) open-label studies and (B) randomized controlled trials. Abbreviations: ABCD, amphotericin B colloidal dispersion; ABLC, amphotercin B lipid complex; CAS, caspofungin; ITZ, itraconazole; LAMB, liposomal amphotericin B; MFG, micafungin; VOR, voriconazole.

and those caused by Zygomycetes (26,27). However, this strategy has not consistently demonstrated improved outcomes in patients with invasive pulmonary aspergillosis. Similar response rates were reported in patients with invasive aspergillosis who received liposomal amphotericin B doses of either 1 or 4mg/kg/day in one randomized multicenter trial (28). Other uncontrolled studies have suggested that dose of up to 7.5mg/kg/day of lipid formulations of amphotericin B are relatively well tolerated (29,30). In contrast, a recent study demonstrated that doses of 10mg/kg/day of liposomal amphotericin B did not improve outcomes compared to doses of 3mg/kg/day but were associated with increased toxicity (31).

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