Increasing Efficacy of Antibiotic by Combining it with Adjuvants against Resistant Gram-Negative and Gram- Positive Bacteria

Abstract

Bacterial resistance to currently available treatments is a global problem that raises death rates and treatment costs, emphasizing the need for additional classes of antibacterial drugs or compounds that interact synergistically with antimicrobials. The efficacy of current antibiotics has been considerably compromised by the rapid spread and emergence of antimicrobial resistance in both Gram-positive and Gram-negative pathogens. The objective of current study is to improve antibiotic efficacy by combining ciprofloxacin, amikacin, ceftriaxone, vancomycin and colistin with adjuvants i.e., iron nanoparticles (FeNP), rhamnose, isatin and sinapic acid. Zone of inhibition (ZoI) measurements and minimum inhibitory concentration (MIC) assays were used to evaluate these combinations antibacterial effectiveness against clinically relevant resistant strains of P. aeruginosa and S. aureus. The findings emphasize the potential of adjuvant therapy in overcoming antibiotic resistance. Fe-NP frequently counteracted antibiotic activity, raising MIC values in the majority of combinations despite slight increase in ZoI. Rhamnose exhibited variable outcomes, increasing MIC in some combinations and reducing it in others. Isatin improved antibiotic performance by lowering MIC and increase in ZoI for ciprofloxacin against S. aureus and amikacin and ceftriaxone against P. aeruginosa. Sinapic acid demonstrated selective but potent synergy, especially with ciprofloxacin and amikacin against resistant P. aeruginosa. These results suggest that certain adjuvants, especially isatin and sinapic acid enhanced the activity of antibiotics. Such combinations could enable lower antibiotic doses, reduce side effects and delay the emergence of resistance.