Interaction of local anaesthetics with other antifungal agents against pathogenic Aspergillus

Acacio Gonçalves Rodrigues1, Ricardo Araujo, Cidalia Pina-Vaz

  • 1Department of Microbiology, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal. acaciorodrigues@hotmail.com

Insights

Local anesthetics (LAs) inhibit Aspergillus fungal growth and germination. LAs interact with antifungal drugs, potentially altering treatment efficacy in immunocompromised patients.

Area of Science:

  • Medical Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Aspergillus species cause significant infections in immunocompromised individuals.
  • Local anesthetics (LAs) exhibit antimicrobial properties against bacteria and yeasts.
  • Understanding drug interactions is crucial for managing invasive fungal infections.

Purpose of the Study:

  • To investigate the effects of LAs (lidocaine, bupivacaine) on Aspergillus species germination and conidial viability.
  • To evaluate the in vitro interactions between LAs and common antifungal agents.
  • To explore the role of calcium ions in modulating LA-induced inhibition.

Main Methods:

  • Assessing the impact of subinhibitory and higher concentrations of LAs on Aspergillus conidial germination.
  • Evaluating the combined effects of LAs with amphotericin B, itraconazole, caspofungin, and voriconazole.
  • Investigating the influence of calcium chloride on LA and verapamil/nifedipine-induced inhibition.

Main Results:

  • Subinhibitory concentrations of lidocaine and bupivacaine inhibited germination of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger.
  • LAs demonstrated synergistic effects with amphotericin B, itraconazole, and caspofungin, but antagonism with voriconazole.
  • Higher LA concentrations exhibited fungicidal activity against conidia by causing cell membrane damage.
  • Verapamil, nifedipine, and lanthanum also inhibited conidial germination, an effect reversed by calcium chloride.

Conclusions:

  • Local anesthetics can inhibit Aspergillus germination and possess fungicidal properties.
  • Drug interactions between LAs and antifungals can significantly modulate treatment outcomes.
  • Calcium ions play a role in the inhibitory effects of certain LAs and calcium channel blockers.

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