Emerging fungal pathogens, drug resistance and the role of lipid formulations of amphotericin B in the treatment of fungal infections in cancer patients: a review.
The incidence of life-threatening invasive fungal infections in immunocompromised patients has increased dramatically in recent years. Candida spp other than C. albicans are increasingly being isolated, and Aspergillus infections also are on the increase, as well as infections due to previously uncommon organisms. It is likely that this phenomenon is multifactorial in origin, although the extensive use of antifungal prophylaxis may have played a role, especially for the emergence of non-albicans Candida. Amphotericin B remains the antifungal agent with the broadest spectrum of action available and is thus the standard treatment for immunocompromised patients with proven or suspected fungal infections, especially aspergillosis. However, its potential for nephrotoxicity limits its usefulness. Lipid formulations of amphotericin B may allow therapy to be administered with reduced renal toxicity. Three different lipid formulations of amphotericin B currently are available. These compounds have different pharmacokinetic properties and seem to achieve higher serum or tissue concentrations than amphotericin B. This statement is based on animal models and scattered human data. At present, there are no studies comparing the lipid formulations with each other and only a few randomized trials comparing them with conventional amphotericin B. However, a number of open clinical trials and compassionate-use protocols suggest that lipid-based forms of amphotericin B can achieve good response rates with minimal toxicity in patients with a variety of invasive mycoses, including those who have proved refractory or intolerant to previous therapy with conventional amphotericin B. Unfortunately, the cost of these compounds remains high and may represent a limiting factor to their use.
Viscoli
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Immunocompromised Host Unit, University of Genoa and National Institute for Cancer Research, Genoa, Italy.
Castagnola
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D000666:Amphotericin B / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000737:chemistry / Q000627:therapeutic use*; D001230:Aspergillus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003102:Colloids / Q000627:therapeutic use; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D017964:Itraconazole / Q000627:therapeutic use; D008081:Liposomes / Q000627:therapeutic use; D009181:Mycoses / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality; D009369:Neoplasms / Q000150:complications* / Q000401:mortality; D010713:Phosphatidylcholines / Q000627:therapeutic use; D010715:Phosphatidylglycerols / Q000627:therapeutic use
D000935:Antifungal Agents; D003102:Colloids; D004338:Drug Combinations; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole