Alternative Approaches to Counter Multidrug-Resistant Bacterial Pathogens

The discovery of antimicrobials has had a significant impact on the reduction of deaths related to infectious diseases. However, this advancement was no sooner followed by the emergence of resistance against these antimicrobials. Overuse and misuse of these agents have brought us to a pre-antibiotic world, with extremely limited agents targeting quickly evolving multidrug-resistant (MDR) bacterial pathogens. This scenario highlights the need to develop strategies to discover novel antibiotics that can overcome at least the presently known resistance mechanism. This review covers the newly emerging strategies that not only bypass the bacterial resistance mechanism but also potentiate available antibiotics against MDR bacterial pathogens. These nonantibiotic approaches include targeted antibacterial photodynamic therapy (APT) and phage therapy, bacterial protein degradation via BacPROTAC, genome editing utilizing clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein (Cas), reduction of bacterial pathogenesis by anti-virulence strategies such as targeting specialized secretion systems, regulating virulence gene expression and toxin production, and reducing drug-associated toxicity by utilizing biomimetic assemblies and surfaces, using immunotherapies and vaccines, and modulating the gut microbiome via fecal microbiota transplantation (FMT), prebiotics, probiotics, postbiotics, and hemofiltration devices. Additionally, this chapter explores the exciting advancements on the horizon, such as personalized medicine, nanotechnology-based therapies, and genome mining and artificial intelligence (AI)-driven approaches. In addition, this chapter discusses the potential of these innovations on the treatment landscape and the hope that they bring by overcoming antibiotic resistance associated with MDR bacterial pathogens.