Breaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae

Klebsiella pneumoniae is a leading cause of anti-microbial resistance in healthcare-associated infections that have posed a severe threat to neonatal and wider community. The escalating crises of antibiotic resistance have compelled researchers to explore an innovative arsenal beginning from natural resources to chemical modifications in order to overcome the ever-increasing resistance issues. The present review highlights the drug discovery efforts with a special focus on cutting-edge strategies in the hunt for potential drug candidates against MDR/XDR Klebsiella pneumoniae. Nature's bounty constituting plant extracts, essential oils, fungal extracts, etc. holds promising anti-bacterial potential especially when combined with existing antibiotics. Further, enhancing these natural products with synthetic moieties has improved their effectiveness, creating a bridge between the natural and synthetic world. Conversely, the synthetically modified novel scaffolds have been also designed to meticulously target specific sites. Furthermore, we have also elaborated various emerging strategies for broad-spectrum infections caused by K. pneumoniae, which include anti-microbial peptides, nanotechnology, drug repurposing, bacteriophage, photodynamic, and multidrug therapies. This review further addresses the challenges confronted by the research community and the future way forward in the field of drug discovery against multi-resistant bacterial infections.