New Oral Amphotericin B Offers Promising Treatment for Cryptococcal Meningitis
Cryptococcal meningitis is a severe fungal infection, often associated with human immunodeficiency virus (HIV). The gold standard treatment for such infections has traditionally been intravenous amphotericin B. However, a new orally delivered formulation of amphotericin B offers a less toxic and potentially more accessible treatment option.
A randomized clinical trial Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America by David R Boulware and colleagues assessed the efficacy and safety of oral lipid nanocrystal (LNC) amphotericin B, known as MAT2203, compared to intravenous (IV) amphotericin B in treating cryptococcal meningitis among individuals with HIV. The trial comprised four cohorts, including safety, tolerability, and efficacy assessments. The findings of the study were:
● Efficacy Confirmed: The primary endpoint of cerebrospinal fluid (CSF) early fungicidal activity (EFA) was met in all groups, demonstrating the antifungal effectiveness of LNC amphotericin B. The mean EFA was comparable between oral LNC amphotericin B groups and IV amphotericin controls.
● High CSF Sterility Rates: Both oral LNC amphotericin B groups achieved 2-week CSF sterility in a substantial percentage of cases, with 63% and 68% success rates, respectively, compared to 68% in the IV amphotericin control group.
● Survival Rates: The 18-week survival rates were encouraging, with 85% for all-oral LNC amphotericin, 90% for oral LNC amphotericin with IV loading doses, and 85% for IV amphotericin controls.
● Reduced Toxicity: Grade 3-4 laboratory adverse events occurred less frequently in the LNC amphotericin groups (41%) compared to the IV amphotericin group (61%). This was particularly notable for anaemia (21% vs. 44%) and potassium-related issues (5% vs. 17%).
The results of this study suggest that the new oral amphotericin B LNC formulation holds promise for the treatment of cryptococcal meningitis. It demonstrated antifungal activity on par with IV amphotericin while offering similar survival rates. Most notably, the oral formulation showed significantly less toxicity, making it a more tolerable option for patients.
Cryptococcal meningitis, especially in the context of HIV, has been a challenging condition to treat effectively. The development of an oral amphotericin B LNC formulation represents a significant advancement in antifungal therapy. Not only does it show promise in terms of efficacy and survival rates, but it also addresses the critical issue of treatment-related toxicity. This innovation brings new hope for individuals battling this life-threatening infection.
Reference:
Boulware, D. R., Atukunda, M., Kagimu, E., Musubire, A. K., Akampurira, A., Tugume, L., Ssebambulidde, K., Kasibante, J., Nsangi, L., Mugabi, T., Gakuru, J., Kimuda, S., Kasozi, D., Namombwe, S., Turyasingura, I., Rutakingirwa, M. K., Mpoza, E., Kigozi, E., Muzoora, C., … Meya, D. B. (2023). Oral lipid nanocrystal amphotericin B for cryptococcal meningitis: A randomized clinical trial. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. https://doi.org/10.1093/cid/ciad440
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