1. It is interesting to note that this formulation is delivered in a normal saline infusion. All Amphotericin B formulations, including the conventional deoxycholate and all currently available lipid formulations carry explicit pre-cautions regarding incompatibility of Amphotericin B and saline solutions. How does this current preparation get around this incompatibility?

2. It should also be noted that LD 50 for Ambisome® is 175 mg/kg, a more accurate value than the <17.5 mg/kg cited in the article. This is a ten-fold greater value than that of the current liposomal preparation being described.

3. To claim a 100% response rate in the assessable cases fails to consider the fact that the patients who died or were otherwise non-evaluable could have had persisting fungal infections and in fact, may have been treatment failures. This is the rationale behind an intent-to-treat analysis, where all patients who receive atleast one dose of study drug treatment must be included in the efficacy analysis. Viewed in this way according to the results presented in Table I of the article, 13 of 23 patients treated had favourable outcomes, a response rate of 56.5%.

4. It should also be noted that all patients in this report had infections with Candida albicans. The other reports referenced included cases of non-albicans species of Candida as well, which are known to be more difficult to treat and many require longer courses of treatment. Thus, the response rate of treatment as well as the total doses of Amphotericin B needed to treat in this paper are not appropriately comparable to those reported in the references cited.

5. Too many patients in this study have required significant amount of blood transfusion. Authors do not mention whether that was due to ongoing sepsis or an adverse effect of the drug itself.

6. Step up doses (or inability to use an optimal dose) right from the begining may be deterimental to the outcome of such life threatening infections, as systemic fungosis. In such patients, we have often used successfully, de-escalting standard doses of liposomal Amphotericin B (Ambisome®). This could be the reason behind compro-mised efficacy with the novel prepara-tion in this study.

7. Also three of the authors of the current study are the manufacturers of this new molecule. So surely there would be a conflict of interest in reporting the results of this pilot study.

8. In our own experience of significant and severe fungal infections in immuno-competent and immunocompromized patients, the use of coventional Ampho-tericin B has been fraught with serious nephrotoxicity or adverse effects during administration of the drug, invariably forcing us to go back to standard lipo-somal Amphotericin B (Ambisome®).

9. As a small noncomparative phase 2 trial, these results do not provide any proof that this liposomal preparation of Amphotericin B is comparable in safety or efficacy to the currently available Amphotericin B products. Larger, controlled prospective trials in both children and adults, against a variety of clinically relevant fungal pathogens, comparing this agent to both Ampho-tericin B deoxycholate and the standard liposomal Amphotericin B product (Ambisome®) are needed in order to fully assess the relative merits of this new fungal formulation.