ABSTRACT
Aim: To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant Pseudomonas aeruginosa. Methods: The effect of the compounds was evaluated in planktonic cells and bacterial biofilms. Accumulation tests were performed with ethidium bromide to prove their action as EPIs. Then, they were associated with antimicrobials. Results: Effect on planktonic cells and biofilms was found. Assays with ethidium bromide indicate their action as EPIs. Significant reductions in the metabolic activity of biofilms were observed after the association with the antimicrobials, especially for meropenem. Conclusion: It is possible to prove the action of these compounds as EPIs for P. aeruginosa and demonstrate the relevance of efflux pumps in antimicrobial resistance.
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Subject(s)
Anti-Bacterial Agents , Biofilms , Drug Repositioning , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Pseudomonas aeruginosa/drug effects , Drug Resistance, Multiple, Bacterial/drug effects , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology , Promethazine/pharmacology , Membrane Transport Proteins/metabolism , Humans , Bacterial Proteins/metabolism , Bacterial Proteins/antagonists & inhibitors , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , HydrazonesABSTRACT
AIM: To investigate the direct effect of antibiotics on growth and virulence of the major Candida species associated with invasive infections. MATERIALS & METHODS: Cefepime, imipenem, meropenem, amoxicillin and vancomycin were tested at twofold the peak plasma concentration (2× PP) and the peak plasma concentration (PP). The effects of antibiotics on Candida albicans, Candida parapsilosis, Candida krusei and Candida tropicalis were investigated by colony counting, flow cytometry, proteolytic activity and virulence in Caenorhabditis elegans. RESULTS: Antibiotics increase growth and proteolytic activity of Candida spp; In addition, amoxicillin potentiates virulence of C. krusei and C. tropicalis against Caenorhabditis elegans. CONCLUSION: These results suggest that antimicrobial therapy may have a direct effect on the pathophysiology of invasive fungal infections in patients at risk.
