Among multiple approaches to combating antimicrobial resistance, a combination
therapy of existing
antibiotics with bacterial membrane-perturbing agents is promising. A viable platform of metallopolymers as adjuvants in combination with traditional
antibiotics is reported in this work to combat both planktonic and stationary cells of Gram-negative superbugs and their biofilms. Antibacterial efficacy, toxicity, antibiofilm activity, bacterial resistance propensity, and mechanisms of action of metallopolymer-
antibiotic combinations are investigated. These metallopolymers exhibit 4-16-fold potentiation of
antibiotics against Gram-negative bacteria with negligible toxicity toward mammalian cells. More importantly, the lead combinations (
polymer-
ceftazidime and
polymer-
rifampicin) eradicate preformed biofilms of MDR E. coli and P. aeruginosa, respectively. Further, β-lactamase inhibition, outer membrane permeabilization, and membrane depolarization demonstrate synergy of these adjuvants with different
antibiotics. Moreover, the membrane-active metallopolymers enable the
antibiotics to circumvent bacterial resistance development. Altogether, the results indicate that such non-
antibiotic adjuvants bear the promise to revitalize the efficacy of existing
antibiotics to tackle
Gram-negative bacterial infections.