Antimicrobial drug resistance has emerged as a significant public health challenge, exacerbated by the rise of multidrug-resistant strains and the emergence of new infections. This has intensified the need for the development of novel therapeutic agents. Antibiotics, originally derived from microorganisms, are compounds that either inhibit or kill other microbes. Historically, most antibiotics used in clinical settings were produced by Actinomycetes and fungi, particularly during the golden age of antibiotic discovery (1940s to 1960s). However, progress in drug development slowed in the following decades due to challenges in cultivation techniques, including isolation difficulties, microbial overgrowth, and discrepancies between natural environments and laboratory conditions. Recently, innovative approaches, such as advancements in cultivation methods, modification of existing compounds, gene induction, exploration of animal microbiota, co-cultivations, and identification of alternative antimicrobial targets, have provided new pathways for drug discovery. Additionally, cutting-edge molecular tools like metagenomics have enabled the exploration of bioactive molecules from uncultured microbes in diverse microenvironments, potentially ushering in a new era in antibiotic development. This review examines both past and current methodologies in antimicrobial drug discovery, highlighting future perspectives for the field.

Urinary tract infections (UTIs) are a major cause of hospital-acquired infections, and up to 80% of these are linked to urinary catheters. The biofilm formation of uropathogenic E. coli plays a critical role in the development of catheter-associated urinary tract infections (CAUTIs). This study aimed to develop a silicone elastomer material incorporating green-synthesized zinc oxide nanoparticles for potential urinary catheter applications and assess its antibiofilm efficacy against uropathogenic Escherichia coli (UPEC). E. coli was identified by the BD Phoenix^TM system and 16S rRNA gene sequencing. ZnO NPs were synthesized through a green method using Crataegus azarolus leaf extract as a biological reducing and stabilizing agent. NPs were incorporated into a silicone matrix at different concentrations (0 wt%, 0.5 wt%, 1 wt% and 1.5 wt%) to produce ZnO-functionalized silicone elastomer specimens for potential urinary catheter applications, and then their antibiofilm activity was assessed through a 96-well microtiter assay. NPs and nanocomposites were characterized through various spectroscopic techniques using XRD, FTIR, and FESEM. In the 1.5 wt% ZnO NPs–silicone elastomer specimen, biofilm formation by E. coli ATCC 25922 and the clinical isolate were significantly reduced by 86.94% and 78.40%, respectively, compared to the control silicone elastomer specimen for potential urinary catheter application. The present findings suggest that green synthesized ZnO NPs provide a promising and biocompatible approach to reducing UPEC biofilm formation when incorporated into silicone elastomer specimens for urinary catheter application. Furthermore, this method may help reduce CAUTIs in clinical settings.