Phytochemical Composition, Antibacterial, and Antibiotic-Resistance Modulatory Activity of Extracts of Lippia multiflora Moldenke, Terminalia mollis M. A. Lawson, and Cinchona officinalis L. Against Multidrug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a critical-class pathogen that shows great resistance to most conventional antibiotics. Hence, it is of utmost importance to search for novel drugs to fight infections caused by this bacterium. This study aimed to evaluate the antibacterial activity of Lippia multiflora, Terminalia mollis, and Cinchona officinalis extracts alone and in combination with antibiotics against multidrug-resistant (MDR) P. aeruginosa. Phytochemical analysis was performed using standard qualitative and quantitative assays. The microdilution method was used to assess the antibacterial and antibiotic-resistance modulatory activity of the extracts. The interaction between antibiotics and Cinchona officinalis leaf extract was carried out using the checkerboard broth microdilution method. Phenols and flavonoids were detected in all extracts, whereas other phytochemical classes were selectively distributed. T. mollis leaf extract demonstrated the highest phenolic content (151.59 mg GAE/g), while L. multiflora leaf (LML) extract showed the highest flavonoid content (24.51 mg QE/g). These extracts exhibited antibacterial activity, with minimum inhibitory concentrations (MICs) ranging from 128 to 2048 μg/mL. LML extract displayed the best antipseudomonal activity, with MIC of 128 μg/mL against ATCC 27853 and 256 μg/mL against some MDR isolates (PA1, PA2, and PA7). Moreover, C. officinalis leaf extract (MIC/8), although weakly active, had improved by 2 to 64-fold the activity of imipenem, streptomycin, kanamycin, and ceftriaxone against MDR P. aeruginosa. It also showed synergy (ΣFIC ≤ 0.5) with streptomycin, ampicillin, tetracycline, and vancomycin against P. aeruginosa PA3. The overall results indicate that the tested extracts, especially those from L. multiflora and C. officinalis leaves, necessitate further exploration for the development of natural drugs to treat infections caused by MDR P. aeruginosa.