Treatment of serious P. aeruginosa infections becomes more challenging with each passing year. As this pathogen acquires
more transferrable resistance mechanisms and continues to rapidly adapt and emerge resistant during the course of antimicrobial therapy,
we face the growing threat of pan-resistance. This review has focused on those mechanisms that directly impact the future of β-lactam
antibiotics, including the production of β-lactamases, porin-mediated resistance, and/or the overexpression of RND efflux pumps. With
the pipeline of new anti-pseudomonal agents diminishing, it is essential that novel therapeutic strategies be explored. These include targeting
biofilm formation and maintenance, virulence factors, and resistance mechanisms. Furthermore, we must continue to search for effective
antibacterial combinations to not only prevent further emergence of resistance but also treat resistant strains already in the environment.