Ceftazidime-Decorated Gold Nanoparticles: a Promising Strategy against Clinical Ceftazidime-Avibactam-Resistant Enterobacteriaceae with Different Resistance Mechanisms

Nanoparticle-based antibiotic delivery systems are essential in combating antibiotic-resistant bacterial infections arising from acquired resistance and/or biofilm formation. Here, we report that the ceftazidime-decorated gold nanoparticles (CAZ_Au NPs) can effectively kill clinical ceftazidime-avibactam-resistant Enterobacteriaceae with various resistance mechanisms. Nanoparticle-based antibiotic delivery systems are essential in combating antibiotic-resistant bacterial infections arising from acquired resistance and/or biofilm formation. Here, we report that the ceftazidime-decorated gold nanoparticles (CAZ_Au NPs) can effectively kill clinical ceftazidime-avibactam-resistant Enterobacteriaceae with various resistance mechanisms. Further study of underlying antibacterial mechanisms suggests that CAZ_Au NPs can damage the bacterial cell membrane and increase the level of intracellular reactive oxygen species. Moreover, CAZ_Au NPs show great potential in inhibiting biofilm formation and eradicating mature biofilms via crystal violet and scanning electron microscope assays. In addition, CAZ_Au NPs demonstrate excellent performance in improving the survival rate in the mouse model of abdominal infection. In addition, CAZ_Au NPs show no significant toxicity at bactericidal concentrations in the cell viability assay. Thus, this strategy provides a simple way to drastically improve the potency of ceftazidime as an antibiotic and its use in further biomedical applications.

Automated summary

Nanoparticle-based antibiotic delivery systems, such as ceftazidime-decorated gold nanoparticles (CAZ_Au NPs), effectively kill ceftazidime-avibactam-resistant Enterobacteriaceae with various resistance mechanisms and inhibit biofilm formation. CAZ_Au NPs damage bacterial cell membrane, increase intracellular reactive oxygen species, and exhibit no significant toxicity at bactericidal concentrations. Furthermore, they improve survival rate in a mouse model of abdominal infection, making them a promising approach to enhance the potency of ceftazidime as an antibiotic.