Abstract
Development of vancomycin resistance by some microbial strains, partly due to permeation problems, has made treatment of some bacterial infections very difficult. Some natural compounds, including terpenes, are known for their antimicrobial activities and also their permeation enhancement effects. The aim of this study was to investigate the possibility of improvement of vancomycin antibacterial effect in combination with terpenes. To perform this investigation, antibacterial activity of vancomycin and three terpenes, cineole, limonene, and eugenol, alone (minimum inhibitory concentration) and in combination (fractional inhibitory concentration index) against vancomycin-resistant Enterococcus faecium and Escherichia coli and vancomycin-sensitive Staphylococcus aureus, was evaluated. Results showed excellent synergism in vancomycin/cineole and vancomycin/limonene systems against E. faecium with fractional inhibitory concentration indices of 0.03 and 0.12 respectively, 512-fold decrease in minimum inhibitory concentration from 0.4 to 0.0009 mM, and that E. faecium has turned vancomycin-sensitive by both terpenes. Results also revealed great synergism in vancomycin/cineole and vancomycin/limonene systems against E. coli with fractional inhibitory concentration indices of 0.25 and 0.35, respectively. The fractional inhibitory concentration index of 0.49 against E. faecium and 0.50 against E. coli indicated good synergism between eugenol and vancomycin. All terpenes had additive effects against vancomycin-sensitive S. aureus.
Graphical Abstract
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Acknowledgements
This work is a part of Ph.D. thesis of F. Sadeghi at the Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran, and was financially supported by SBMU.
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This work was financially supported by Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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HRM and AM conceptualized and designed the investigation. FS performed the experiments and data collection. Data were analyzed by all authors. The manuscript was drafted by FS and read, confirmed, and finalized by HRM, AM, and JR.
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Sadeghi, F., Mahboubi, A., Ranjbari, J. et al. Overcoming Vancomycin Resistance in Enterococcus faecium and Increased Efficacy in Escherichia coli and Staphylococcus aureus by Cineole, Limonene, and Eugenol Permeation Enhancers. Rev. Bras. Farmacogn. 32, 1033–1037 (2022). https://doi.org/10.1007/s43450-022-00301-6
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DOI: https://doi.org/10.1007/s43450-022-00301-6