Combination of drugs: An effective approach for enhancing the efficacy of antibiotics to combat drug resistance

Abstract

Currently available antibiotics have been effective in treating infectious diseases; however, the development of resistance to these drugs has led to the emergence of new and the re-emergence of old, infectious diseases. Therefore, newer antibiotic approaches with mechanistic differences are needed to combat antimicrobial resistance. Combining antibiotics is an encouraging strategy for increasing treatment efficacy and for controlling resistance evolution. This approach may include the combination of one antibiotic with another antibiotic and the development of adjuvants that either directly target resistance mechanisms, like inhibition of β-lactamase enzymes, or indirectly target resistance by interrupting the bacterial signaling pathways, such as two-component systems. Other natural products, like essential oils, plant extracts, and nanoparticles, can also be combined synergistically with antibiotics. The aim of this chapter is to highlight the strategy of treating infections with arrays of drugs rather than discrete drugs. We have addressed here three categories of approaches being used in combination therapy: the inhibition of targets in different pathways, the inhibition of distinct nodes in the same pathway, and the inhibition of the same target in different ways. Here, we have described the most recent developments toward combination therapies for the treatment of infectious diseases caused by multidrug-resistant bacteria.