Antifungal activity of local anesthetics against Candida species.
OBJECTIVE
To evaluate the activity of benzydamine, lidocaine, and bupivacaine, three drugs with local anesthetic activity, against Candida albicans and non-albicans strains and to clarify their mechanism of activity.


METHODS
The minimal inhibitory concentration (MIC) was determined for 20 Candida strains (18 clinical isolates and two American Type Culture Collection strains). The fungistatic activity was studied with the fluorescent probe FUN-1 and observation under epifluorescence microscopy and flow cytometry. The fungicidal activity of the three drugs was assayed by viability counts. Membrane alterations induced in the yeast cells were evaluated by staining with propidium iodide, by quantitation of intracellular K+ leakage and by transmission electron microscopy of intact yeast cells and prepared spheroplasts.


RESULTS
The MIC ranged from 12.5-50.0 microg/mL, 5.0-40.0 mg/mL, and 2.5-10.0 mg/mL for benzydamine, lidocaine, and bupivacaine, respectively. The inhibitory activity of these concentrations could be detected with the fluorescent probe FUN-1 after incubation for 60 minutes. A very fast fungicidal activity was shown by 0.2, 50, and 30 mg/mL of benzydamine, lidocaine, and bupivacaine, respectively.


CONCLUSIONS
At lower concentrations, the tested drugs have a fungistatic activity, due to yeast metabolic impairment, while at higher concentrations they are fungicidal, due to direct damage to the cytoplasmic membrane.
Pina-Vaz
C
C
Department of Microbiology, Porto School of Medicine, University of Porto, Portugal. micfam@ip.pt
Rodrigues
A G
AG
Sansonetty
F
F
Martinez-De-Oliveira
J
J
Fonseca
A F
AF
Mårdh
P A
PA
D000362:Agar; D000779:Anesthetics, Local / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001591:Benzydamine / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D002177:Candidiasis / Q000382:microbiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D015169:Colony Count, Microbial; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D013997:Time Factors
D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000935:Antifungal Agents; D001591:Benzydamine; D000362:Agar; D008012:Lidocaine; D002045:Bupivacaine