Lipid amphotericin B combinations; 'la crème de la crème'?

Abstract

Fungal infections are significant causes of mortality and morbidity in seriously ill and immunocompromised patients. Their frequency has risen because of changes in the epidemiology of predisposing diseases such as the spread of AIDS, or in management, including the development of techniques such as bone marrow transplantation (BMT). The widescale use of control measures, including antibiotics, for infection has also affected the distribution of fungal infections and there has been a concomitant increase in antifungal drug resistance against azole antifungals, particularly amongst pathogenic yeasts as well as the emergence of new fungal pathogens, such as Trichosporon, Fusarium, Bipolaris and Scedosporium.’ A multicentre survey of 16 hospitals in Europe found that 22% of patients dying with acute leukaemia had systemic fungal infection found at autopsy, the range being 12-46%.? Yet the mortality of the commonest systemic mycoses, aspergillosis and candidosis remains very high in the neutropenic patient; untreated it approaches 100% and even with conventional treatment it is greater than 70% for aspergillosis and somewhat less for Candida infections. This combination of an unmet clinical need, new organisms and the emergence of drug resistance has placed a premium on the quest for better antifungal treatments. Amphotericin B remains the treatment option of choice for many of these infections, although fluconazole has a clear role in certain diseases and clinical situations such as candidemia due to Candida albicans in the Intensive Care Unit (KU). Factors which are thought to be important in the continued interest in amphotericin B (AMB) are it’s broad in vitro spectrum of activity, the ability to achieve adequate levels rapidly following intravenous infusion and the very low risk of drug resistance. The down side of the drug is the high frequency of adverse reactions such as hyperpyrexia, renal tubular damage leading to renal failure,j hypokalaemia and anaemia”,j coupled with poor penetration into areas such as the urine and cerebrospinal fluid (CSF). However, it has been possible to mitigate some of AMBs disadvantages although the most important of