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The widespread occurrence of infections from multidrug-resistant (MDR) bacteria is a global health problem. It has been amplified over the past few years due to the increase in adaptive traits in bacteria and lack of advanced treatment strategies. Because of the low bioavailability and limited penetration at infected sites, the existing antibiotics often fail to resist bacterial growth. Recently, developed stimuli-responsive drug delivery systems and combinatorial therapeutic systems based on nanoparticles, metal−organic frameworks, hydrogels, and organic chromophores offer the ability to improve the therapeutic efficacy of antibiotics by reducing drug resistance and other side effects. These therapeutic systems have been designed with the relevant chemical and physical properties that respond to specific triggers resulting in spatiotemporal controlled release and site-specific transportability. This review highlights the latest development of single and dual/multistimuli-responsive antibiotic delivery systems for combination therapies to treat MDR bacterial infections and biofilm eradication.

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