Microbial resistance to classical antibiotics and its rapid progression have raised serious concern in the treatment of infectious diseases. Recently, many studies have been directed towards finding promising solutions to overcome these problems. Phytochemicals have exerted potential antibacterial activities against sensitive and resistant pathogens via different mechanisms of action. In this review, we have summarized the main antibiotic resistance mechanisms of bacteria and also discussed how phytochemicals belonging to different chemical classes could reverse the antibiotic resistance. Next to containing direct antimicrobial activities, some of them have exerted in vitro synergistic effects when being combined with conventional antibiotics. Considering these facts, it could be stated that phytochemicals represent a valuable source of bioactive compounds with potent antimicrobial activities.

The extensive usage of antibiotics and the rapid emergence of antimicrobial-resistant microbes (AMR) are becoming important global public health issues. Many solutions to these problems have been proposed, including developing alternative compounds with antimicrobial activities, managing existing antimicrobials, and rapidly detecting AMR pathogens. Among all of them, employing alternative compounds such as phytochemicals alone or in combination with other antibacterial agents appears to be both an effective and safe strategy for battling against these pathogens. The present review summarizes the scientific evidence on the biochemical, pharmacological, and clinical aspects of phytochemicals used to treat microbial pathogenesis. A wide range of commercial products are currently available on the market. Their well-documented clinical efficacy suggests that phytomedicines are valuable sources of new types of antimicrobial agents for future use. Innovative approaches and methodologies for identifying plant-derived products effective against AMR are also proposed in this review.

Antibiotic resistance has stimulated the research for developing novel strategies that can prevent bacterial growth. Methicillin-resistant Staphylococcus aureus (MRSA), regarded as one of the most serious antibiotic-resistant bacteria which has been conventionally recognized as a nosocomial pathogen. Nanoliposomal formulations of piperine and gentamicin were prepared by dehydration-rehydration (DRV) method and characterized for size, zeta potential and encapsulation efficiency. Antibactericidal activities of liposomal and free forms were evaluated against MRSA ATCC 43300 by the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and fractional inhibitory concentration index (FICI). The time-kill studies were carried out to evaluate the potency of antibacterial agents. The effect of piperine on bacterial efflux pumps was also investigated. MIC values of gentamicin and piperine were 32 and 100 µg/mL, respectively. Synergetic effects were observed by the combination of gentamicin and piperine and FICI was determined to be 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 16- and 32-fold, respectively. MBC values of gentamicin reduced 4 and 8 times following incorporation into gentamicin and combination liposomes, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective preparations in time-kill study. Our findings indicated that liposomal piperine was able to inhibit the efflux pump sufficiently. The results of this study revealed that liposomal combination is a powerful nano-antibacterial agent to eradicate MRSA infection. This dual-loaded formulation was an effective approach for eradication of MRSA.