Despite the discovery and development of an array of antimicrobial agents, multidrug resistance poses a major threat to public health and progressively increases mortality. Recently, several studies have focused on developing promising solutions to overcome these problems. This has led to the development of effective alternative methods of controlling antibiotic-resistant pathogens. The use of antimicrobial agents in combination can produce synergistic effects if each drug invades a different target or signaling pathway with a different mechanism of action. Therefore, drug combinations can achieve a higher probability and selectivity of therapeutic responses than single drugs. In this systematic review, we discuss the combined effects of different antimicrobial agents, such as plant extracts, essential oils, and nanomaterials. Furthermore, we review their synergistic interactions and antimicrobial activities with the mechanism of action, toxicity, and future directions of different antimicrobial agents in combination. Upon combination at an optimum synergistic ratio, two or more drugs can have a significantly enhanced therapeutic effect at lower concentrations. Hence, using drug combinations could be a new, simple, and effective alternative to solve the problem of antibiotic resistance and reduce susceptibility.
Keywords: antimicrobial agents; bacterial infections; multidrug resistance; pathogen inactivation; synergistic effects.