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Lower Concentrations of Amphotericin B Combined with Ent-Hardwickiic Acid Are Effective against Candida Strains

Maria V Sousa Teixeira1, Jennyfer A Aldana-Mejía1, Márcia E da Silva Ferreira1

  • 1Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café, s/n, Ribeirão Preto 14040-903, Brazil.

Antibiotics (Basel, Switzerland)
|March 29, 2023
PubMed

Insights

Combining ent-hardwickiic acid with amphotericin B significantly lowers antifungal drug concentrations needed to combat Candida infections. This combination therapy offers a promising strategy to reduce side effects and enhance treatment efficacy against resistant strains.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Life-threatening Candida infections are rising, exacerbated by the COVID-19 pandemic.
  • Existing antifungal drug limitations are worsened by side effects linked to SARS-CoV-2 complications.
  • Drug combination strategies can mitigate side effects without compromising therapeutic effectiveness.

Purpose of the Study:

  • To evaluate the synergistic effect of ent-hardwickiic acid combined with low-dose amphotericin B against Candida strains.
  • To determine the impact of this combination on minimum inhibitory concentrations (MICs) and fungicidal activity.

Main Methods:

  • Checkerboard microdilution method to assess 77 combinations of ent-hardwickiic acid and amphotericin B.
  • Determination of MIC values for individual compounds and their combinations.
  • Time-kill assays to evaluate the fungistatic or fungicidal properties of the combinations.

Main Results:

  • The combination markedly reduced amphotericin B MIC from 16 µg/mL to 1 µg/mL and ent-hardwickiic acid MIC from 12.5 µg/mL to 6.25 µg/mL against azole-resistant Candida albicans.
  • A specific combination (1 µg/mL amphotericin B with 6.25 µg/mL ent-hardwickiic acid) eradicated all Candida cells within four hours.

Conclusions:

  • The combination of ent-hardwickiic acid and amphotericin B demonstrates significant synergistic activity against Candida infections.
  • This drug combination presents a viable strategy to reduce antifungal drug dosages and associated side effects.
  • The findings support the development of novel combination therapies for challenging Candida infections.
Keywords:
Candida albicansCandida kruseiamphotericin Bantifungal combinationcheckerboardent-hardwickiic acidresistant straintime–kill curves

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