PAMAM dendrimers with dual-conjugated vancomycin and Ag-nanoparticles do not induce bacterial resistance and kill vancomycin-resistant Staphylococci

The effective life-time of new antimicrobials until the appearance first resistant strains is steadily decreasing, which discourages incentives for commercialization required clinical translation and application. Therefore, development should not only focus on better killing antimicrobial-resistant strains, but as a paradigm shift developing that prevent induction resistance. Heterofunctionalized, poly-(amido-amine) (PAMAM) dendrimers with amide-conjugated vancomycin (Van) incorporated Ag nanoparticles (AgNP) showed 6–7 log reduction in colony-forming-units vancomycin-resistant Staphylococcus aureus strain vitro, while inducing resistance vancomycin-susceptible strain. Healing superficial wound mice infected S. was significantly faster more by irrigation low-dose, dual-conjugated Van-PAMAM-AgNP dendrimer suspension than solution or PAMAM-AgNP suspension. Herewith, dual-conjugation together AgNPs heterofunctionalized PAMAM fulfills need new, prolonged pathogens without susceptible strains. Important translation, this use antibiotics can be achieved currently approved clinically applied antibiotics, provided suitable amide-conjugation.