The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.

This review explores the recent advancements and the enduring challenges in new antibacterial development for drug-resistant organisms.

We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity. Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to overcome the MDR issue.

Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight against superbugs.