Local amphotericin B therapy for Cutaneous Leishmaniasis: A systematic review

PLoS Negl Trop Dis. 2024 Apr 16;18(4):e0012127. doi: 10.1371/journal.pntd.0012127. eCollection 2024 Apr.

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.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Amphotericin B* / administration & dosage
  • Amphotericin B* / therapeutic use
  • Antiprotozoal Agents* / administration & dosage
  • Antiprotozoal Agents* / therapeutic use
  • Humans
  • Leishmaniasis, Cutaneous* / drug therapy
  • Treatment Outcome

Substances

  • Amphotericin B
  • Antiprotozoal Agents

Grants and funding

LLA 001 by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), available at https://www.capes.gov.br. MLF 151891/2022-2 by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), available at http://www.cnpq.br. GC 302069/2022-4 by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), available at http://www.cnpq.br. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.