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Published on: April 19, 2017
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
Abstract:
Aspergillus spp. are responsible for an increasing number of fungal infections in immunocompromised and transplant patients. Local anaesthetics (LAs) are growth inhibitors of bacteria and yeasts. Subinhibitory concentrations of the LAs lidocaine and bupivacaine blocked the germination of Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger whilst also showing a positive interaction in vitro with the antifungal activity of amphotericin B, itraconazole and caspofungin and a negative interaction with voriconazole. At higher concentrations, both LAs present fungicidal activity against resting conidia owing to cell membrane lesions. Verapamil, nifedipine and lanthanum produced a similar inhibitory effect on conidia germination. Calcium chloride reverted the inhibitory effect of verapamil and LAs. This study highlights that drug interactions may affect the clinical efficacy of antifungals, either promoting or limiting their action.
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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