Interaction of local anaesthetics with other antifungal agents against pathogenic Aspergillus

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, Aspergillusflavus and Aspergillusniger 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.