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Antifungal Associations with a Polyelectrolyte Promote Significant Reduction of Minimum Inhibitory Concentrations

Lavínia da V Pereira1,2, Tiago Rizzi1,2, Micaela Federizzi1,2

  • 1Laboratório de Pesquisa Em Micologia Aplicada (LPMA), Universidade Federal Do Rio Grande Do Sul, Rua São Luís 152, Porto Alegre, 90470-440, Brazil.

Current Microbiology
|November 4, 2024
PubMed

Insights

This study explored Poly(diallyldimethylammonium chloride) (PDDA) combined with antifungal drugs to combat rising fungal infections. PDDA significantly boosted drug effectiveness, showing promise for new antifungal treatments.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Rising global incidence of fungal infections, termed a "silent epidemic."
  • Limited antifungal drug options and increasing drug resistance.
  • Drug repositioning and combination therapies offer promising solutions.

Purpose of the Study:

  • To investigate the antifungal activity of Poly(diallyldimethylammonium chloride) (PDDA) in combination with existing antifungal drugs.
  • To evaluate the efficacy of different drug:PDDA ratios against clinical Candida species.
  • To assess PDDA's potential as an adjuvant in novel antifungal formulations.

Main Methods:

  • Broth microdilution technique to determine Minimum Inhibitory Concentration (MIC).
  • Testing combinations of PDDA with amphotericin B (AMB), clioquinol (CLIO), and nitroxoline (NTX).
  • Evaluation against clinically significant Candida species, including resistant strains.

Main Results:

  • PDDA combinations significantly enhanced the activity of tested antifungal drugs against most Candida strains.
  • MIC reductions up to 512-fold were observed, particularly for fluconazole-resistant Candida krusei.
  • The amphotericin B-PDDA combination (1:99 ratio) showed high efficacy against amphotericin B-resistant strains.

Conclusions:

  • Poly(diallyldimethylammonium chloride) (PDDA) demonstrates significant potential as an adjuvant to potentiate existing antifungal drugs.
  • PDDA-antifungal combinations offer a viable strategy to overcome drug resistance and enhance treatment efficacy.
  • This approach could lead to the development of novel, effective antifungal formulations using established drugs.

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