Liposomal forms of amphotericin B - a new "gold standard" in the treatment of invasive mycosis
Liposomal forms of amphotericin B can now be considered the drugs of choice for the treatment of systemic fungal infections with the possibility of using a wide range of doses.
Amphotericin B (AmV) has been used in clinical practice since 1959. For a long time, it was the only drug for the treatment of severe invasive mycosis. Now, the main reason for using AmV as a second-line or reserve drug is its nephrotoxicity and the high frequency of infusion reactions. The liposomal forms of amphotericin B, in particular the lipid complex AmB, the liposomal dispersion AmB and the colloidal AmB, have no such adverse reactions.
In an article published in the journal Clinical Infectious Diseases, Ostrosky-Zeichner L. et al. They have tried to justify the view that the liposomal forms of amphotericin B are by no means inferior in efficacy and superior to ordinary amphotericin B in their tolerance, and there is therefore reason to recommend these forms of drug as the drug of choice for most systemic fungal infections.
In in vitro studies with cryptococci, Candida fungi and certain mycelial fungi, higher BMD and minimal fungicidal concentrations have been shown for all liposomal forms amphotericin B. However, this fact may be associated with a more difficult release of the active drug from lipid molecules, which mainly targets pharmacokinetic changes in the drug in the body, and therefore the data obtained in vitroare difficult to compare with clinical efficacy indicators. This requires research into new ways to determine the activity of the in vitro liposomal forms of amphotericin B against various types of fungi.
At the present time, a sufficient number of multicentre randomized controlled clinical trials have been carried out, which allows us to say with confidence that at least the equivalent efficacy of the liposomal forms of amphotericin B compared to the usual form. of the drug, mainly in terms of patient survival. Some studies have shown a significantly faster response to treatment with forms of liposomes, particularly with cryptococcal meningitis (Leenders et al.). The largest study can be viewed as a multicenter, double-blind, randomized study by Walsh et al. He compared normal and liposomal amphotericin B in the treatment of patients with neutropenic fever. As a result, the two drugs were equally effective, but the use of liposomal amphotericin B was accompanied by fewer side effects. In a comparative study of conventional amphotericin B and its colloidal dispersion in invasive aspergillosis (Bowden et al.), The two drugs showed the same clinical efficacy, however, the frequency of development of nephrotoxicity during use of the colloidal dispersion of amphotericin B was 3 times less likely (12% vs 38%).
Thus, the liposomal forms of amphotericin B can currently be considered as the drug of choice for the treatment of systemic fungal infections with the possibility of using a wide range of doses of 3 mg / kg / day for Candidaspp., Up to 6 mg / kg / day for cryptococcosis or fungal infections caused by mycelial fungi. They should completely replace conventional amphotericin B in cases where its use is dangerous due to the high risk of developing nephrotoxicity in the patient or infusion reactions. However, further clinical trials will be required to select the optimal liposomal form of AmV and the most appropriate dosage regimen for various forms of invasive fungal infections.