1. Local amphotericin B therapy for Cutaneous Leishmaniasis: A systematic review.
- Author
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Alves, Líndicy Leidicy, Freire, Mariana Lourenço, Troian, Isadora Lana, Morais-Teixeira, Eliane de, and Cota, Gláucia
- Subjects
CUTANEOUS leishmaniasis ,AMPHOTERICIN B ,TOPICAL drug administration ,SKIN ulcers ,NEGLECTED diseases - Abstract
Background: Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis. Methodology: Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components. Principal findings: A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5–64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3–82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34–9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified. Conclusions: Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis. Author summary: Cutaneous leishmaniasis (CL) is a neglected disease recognized for causing ulcers distributed throughout the body; such ulcers can be disfiguring and may intrinsically attract a social stigma. Furthermore, the currently available therapeutic arsenal is admittedly limited and associated with significant toxicity. Long therapeutic regimens and parenteral administration have been considered in recent years as a strategy to be replaced. In this scenario, the search for new treatment alternatives for CL is considered a priority by the World Health Organization, which has been expanding its treatment recommendations with alternatives for local use. In this study, we performed an extensive literature search to gather evidence on the efficacy of amphotericin B (AmB) in local administration for the treatment of CL in preclinical or clinical studies. In total, 21 studies, 16 preclinical studies and five clinical studies were identified. The global cure rate for clinical studies addressing intralesional infiltration and topical application was estimated at 56.9% (CI: 41.1–71.4%). High heterogeneity in the design, groups, and route of administration of AmB among studies was observed, requiring caution in interpreting and extrapolating of this pooled rate. In summary, the results show that local routes of administration of AmB are a promising strategy and need to be evaluated in studies with adequate design, enabling the expansion of therapeutic alternatives for the treatment of CL. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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