Avaliação da atividade antimicrobiana de óleos essenciais de Cinnamomum triplinerve e Ocotea diospyrifolia isoladamente e em sinergia com amicacina contra Klebsiella pneumoniae resistente a polimixina B

Abstract

The challenge of antimicrobial resistance represents a growing threat to global health, limiting the effective therapies available for controlling the spread of resistant microorganisms. Given the urgency of this scenario, it is important to search for alternative approaches to combat these microorganisms. Essential oils (EOs), due to their synergistic potential with conventional antimicrobials, emerge as a promising pathway to enhance treatment efficacy. This study aimed to investigate the antimicrobial activity of EOs, Cinnamomum triplinerve (CtEO) and Ocotea diospyrifolia (OdEO), individually and in combination with the conventional antimicrobial amikacin, against clinical isolates of multidrug-resistant Klebsiella pneumoniae. Chemical analysis revealed (E)-nerolidol as the main constituent of CtEO, while OdEO was dominated by α-bisabolol. The antimicrobial activity of CtEO and OdEO was determined using the broth microdilution method. However, both essential oils, when tested alone, did not inhibit the growth of the multidrug-resistant K. pneumoniae clinical isolate. Through the Checkerboard method, combinations of CtEO and OdEO with amikacin (AMK) demonstrated a synergistic interaction, with FICI values = 0.5. The synergy of both combinations demonstrated the ability to significantly decrease biofilm formation of this isolate compared to the growth control. The time to death of the isolate when subjected to the desired concentrations of the combinations was presented within the period of 3 and 2 hours upon contact with the concentrations of CtEO+AMK and OdEO+AMK, respectively. Additionally, the protein leakage assay demonstrated high concentrations of leaked proteins from bacterial cells between 71.6 and 79.16 µg/mL of the combination of CtEO+AMK and OdEO+AMK, respectively, at the respective time points. Both combinations were also evaluated for interaction with red blood cells, showing little to no interaction. The ability of the combinations of CtEO+AMK and OdEO+AMK increased survival rates by 71.6% and 79.16%, respectively, when compared to the infection control in the alternative model Caenorhabditis elegans. In summary, the evaluated combinations showed potential to inhibit the growth of MDR K. pneumoniae, representing a promising alternative to the development of new antimicrobials aimed at treating infections caused by this pathogen.