Chapter 4 - Recent development of antibacterial agents to combat drug-resistant Gram-positive bacteria

Abstract

Bacteria are increasingly developing resistance against the antibiotics of last resort, which has created enormous threats in the face of global public health. In order to address this clinical challenge, there is a continuous effort toward the development of new antibacterial agents aiming to counter infections caused by both Gram-positive and Gram-negative drug-resistant bacteria. The focus of this chapter is majorly on the infections associated with various drug-resistant Gram-positive bacteria and therapeutic regimen for countering them. Among the multiple strategies that have been adopted in the recent past, the discovery of new antibiotics from natural sources, semisynthetic analogs of existing antibiotics, and development of completely synthetic classes of antibacterial agents have gained enormous attention of the scientific community. This chapter aims to provide an overview of all these strategies, focusing on their recent progress in the field. Nature-derived antibiotics that are isolated either from soil or human microbiome are discussed with an emphasis on their in vitro and in vivo antibacterial efficacy as well as mechanisms of action. Semisynthetic analogs of different classes of antibiotics, which showed improved antibacterial potency compared to their parent drugs, are also portrayed. In this regard, various synthetic strategies for the development of semisynthetic analogs have also been illustrated. Furthermore, a plethora of synthetic antibacterial agents that have been developed by different research groups are illustrated with a focus on antimicrobial peptide-inspired antibacterial agents. Finally, the current challenges in the field are delineated followed by future prospective toward further expansion of the antibacterial therapeutics in combating infections caused by drug-resistant Gram-positive bacteria.