Bacterial drug resistance to antibiotics is growing globally at unprecedented levels, and strategies to overcome treatment deficiencies are continuously developing. In our approach, we utilized metal nanoparticles, silver nanoparticles (AgNPs), known for their wide spread and significant anti-bacterial actions, and the high-dose regimen of lincosamide antibiotic, lincomycin, to demonstrate the efficacy of the combined delivery concept in combating the bacterial resistance. The anti-bacterial actions of the AgNPs and the lincomycin as single entities and as part of the combined mixture of the AgNPs-lincomycin showed improved anti-bacterial biological activity in the Bacillus cereus and Proteus mirabilis microorganisms in comparison to the AgNPs and lincomycin alone. The comparison of the anti-biofilm formation tendency, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) suggested additive effects of the AgNPs and lincomycin combination co-delivery. The AgNPs' MIC at 100 μg/mL and MBC at 100 μg/mL for both Bacillus cereus and Proteus mirabilis, respectively, together with the AgNPs-lincomycin mixture MIC at 100 + 12.5 μg/mL for Bacillus cereus and 50 + 12.5 μg/mL for Proteus mirabilis, confirmed the efficacy of the mixture. The growth curve test showed that the AgNPs required 90 min to kill both bacterial isolates. The freshly prepared and well-characterized AgNPs, important for the antioxidant activity levels of the AgNPs material, showed radical scavenging potential that increased with the increasing concentrations. The DPPH's best activity concentration, 100 μg/mL, which is also the best concentration exhibiting the highest anti-bacterial zone inhibition, was chosen for evaluating the combined effects of the antibiotic, lincomycin, and the AgNPs. Plausible genotoxic effects and the roles of AgNPs were observed through decreased Bla gene expressions in the Bacillus cereus and Bla_CTX-M-15 gene expressions in the Proteus mirabilis.

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