Cathelicidin-like Peptide for Resistant Acinetobacter baumannii Control

The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as <i>Acinetobacter baumannii</i>, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance. <b>Background/Objectives</b>: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides-Btn (15-34) and BotrAMP14 from <i>Bothrops atrox</i>, and Ctn (15-34) and CrotAMP14 from <i>Crotalus durissus</i>-against multidrug-resistant <i>A. baumannii</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i> clinical isolates from skin infections, with emphasis on <i>A. baumannii</i>, a WHO priority pathogen. <b>Methods</b>: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against <i>A. baumannii</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i>. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety. <b>Results</b>: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicated <i>A. baumannii</i> within 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC₅₀ > 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem. <b>Conclusions</b>: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens.