Synergistic Interaction of Polymyxin B with Carvacrol: Antimicrobial Strategy Against Polymyxin-Resistant Klebsiella Pneumoniae

Abstract

Objective:

The antimicrobial activities of the synergistic combination of carvacrol and polymyxin B against polymyxin-resistant Klebsiella pneumoniae were evaluated.

Methods:

The methods employed checkerboard assays to investigate synergism, biofilm inhibition assessment and membrane integrity assay. In addition, the study included in vivo evaluation using a mouse infection model.

Results:

The checkerboard method evaluated 48 combinations, with 23 indicating synergistic action. Among these, carvacrol 10 mg/kg plus polymyxin B 2 mg/kg exhibited in vivo antimicrobial activity in a mouse model of infection, resulting in increased survival and a significant decrease in bacterial load in the blood.

Conclusion:

Polymyxin in synergy with carvacrol represents a promising alternative to be explored in the development of new antimicrobials.

Plain language summary

In this study, we wanted to find a new way to fight a bacteria called Klebsiella pneumoniae, which is not easily killed by medication. We mixed two drugs, carvacrol and polymyxin B, to see if they would work together to fight the bacteria. We found that the mixed treatment helped to kill the bacteria. We also tried this mixed treatment in sick mice, and they got better. Our study shows that this mixed treatment might be a new way to fight bacteria that are hard to kill with regular drugs. Next, we hope to learn more about how it works.

Keywords::

• Gram-negative
• monoterpene
• multidrug resistant
• natural product
• synergy effect

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fmb-2023-0070

Financial disclosure

The authors are grateful for financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 408778/2022-9 and 307946/2022-3), Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul (FUNDECT) (76/2023 and 113/2023), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Universidade Federal da Grande Dourados (UFGD). GH de Almeida de Souza received a CNPq junior postdoctoral fellowship through the FUNDECT (76/2023). The authors are grateful to the CNPq for providing grants to S Simionatto. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the Ethics Committee of the Federal University of Grande Dourados (UFGD) under approval numbers 877.292/2014 and 4.014.325/2020, the UFGD Animal Use Ethics Committee (no. 25/18), and Centro Universitário da Grande Dourados (UNIGRAN; no. 080/18).