- PMID: 35440801
- DOI: 10.1038/s41598-022-10393-8
Abstract
This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.
© 2022. The Author(s).
References
-
- Pendleton, J. N., Gorman, S. P. & Gilmore, B. F. Clinical relevance of the ESKAPE pathogens. Expert Rev. Anti. Infect. Ther. 11, 297–308 (2013). – DOI
-
- Magiorakos, A. P. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 18, 268–281 (2012). – DOI
-
- Poirel, L., Jayol, A. & Nordmann, P. Polymyxins: Antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin. Microbiol. Rev. 30, 557–596 (2017). – DOI
-
- Tamma, P. D. et al. Infectious Diseases Society of America Guidance on the treatment of extended-spectrum β-lactamase producing enterobacterales (ESBL-E), carbapenem-resistant enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR- P. aer. Clin. Infect. Dis. 72, 1109–1116 (2012). – DOI
-
- World Health Organization. World Health Organization Model List of Essential Medicines—22nd List. (2021).
Grant support
- 8887.369851/2019-00/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- 130766/2021-6/Conselho Nacional de Desenvolvimento Científico e Tecnológico
- CNPq/FAPESP 14/50891-1/Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, São Paulo State, Brazil), and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM)
- Global Priorities in Cannabinoid Research Excellence Program/University Global Partnership Network (UGPN)
- 18.1.796.60.2 grupo 057/Pró-Reitoria de Pesquisa da USP

