Combination of polymyxin B and Aquilaria malaccensis extract enhanced the killing and inhibited the growth of Acinetobacter baumannii and Klebsiella pneumoniae

ABSTRACT

Aims@#Polymyxins are an important last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Nonetheless, the emergence of polymyxin-resistance and the limiting of polymyxin monotherapy urgently demands its optimisation. Aquilaria malaccensis (Agarwood) has been widely used as traditional medicine. Many parts of the plant including leaves exhibit a considerable in vitro antibacterial activity against microbial pathogens. Exploiting A. malaccensis in combination with polymyxins provides a novel strategy in fighting antimicrobial resistance. The objective of this study was to evaluate the combination effects of A. malaccensis extract with polymyxins against Acinetobacter baumannii and Klebsiella pneumoniae.@*Methodology and results@#In vitro time-kill studies and GC-MS analysis were performed to evaluate the bacterial killing of polymyxin B and extract combination and analyse chemical compounds of the extract, respectively. The combination of polymyxin B (1 mg/L) and A. malaccensis extract (32 mg/mL and 64 mg/mL) treatments exhibited enhanced bacterial killing compared to polymyxin B alone at 4 h and 24 h. Combination treatments also inhibited the bacterial growth of both A. baumannii and K. pneumoniae observed throughout the 24 h. More than sixty compounds including phytol, 9,12-octadecadienal, fatty acid, alkanes and terpenoids were putatively identified as the compounds that likely contributed to the antibacterial activity.@*Conclusion, significance and impact of study@#This study was the first to report the potential application of A. malaccensis extract in combination with polymyxin B in treatment against A. baumannii and K. pneumoniae and can be further investigated and optimized for the treatment of bacterial infectious diseases.