Peptide-based antimicrobial effect against carbapenem-resistant Acinetobacter baumannii: preclinical drug assessment and translational potential

Background: (CRAB) has become a major global public health threat, with limited treatment options and poor clinical outcomes. In this study, we evaluated the potential of antimicrobial peptides as adjuvants in the treatment of CRAB. Methods: synergistic and bactericidal effects of DD-S052P in combination with the US Food and Drug Administration-approved antibiotics against CRAB were assessed using the checkerboard method and time-kill assay. Mice infected with CRAB were used to evaluate the survival-enhancing effects of DD-S052P-based combination therapy. CRAB isolates were obtained from blood samples of patients with bacteremia. Results: synergistic activity against CRAB isolates when combined with ampicillin/sulbactam, ceftolozane/tazobactam, and colistin. Notably, all combinations exhibited bactericidal effects against CRAB isolates in the time-kill assay. Combination therapy with DD-S052P plus colistin yielded a 100% survival rate in the mouse infection models. Conclusion: Our findings indicate that DD-S052P in combination with colistin may represent a promising therapeutic option for CRAB infections. Further research is required to elucidate the mechanisms by which DD-S052P overcomes existing carbapenem resistance and validate its clinical applicability.