Antibiotic resistance is a global problem that requires different strategies, including new types of antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) and drug-resistant Pseudomonas aeruginosa are involved in skin infections, ventilator-associated pneumonia, and bacteremia. This poster reports an improved peptide antibiotic for treating such challenging infections. We designed a minimal peptide verine previously by combining LL-37 membrane-targeting elements with our peptide design concept for systemic use (PNAS 2020;117:19446-19454). Here we advanced verine based on the findings from the antimicrobial peptide database version 6 (APD6; Nucleic Acids Res. 2026;54:D363-D374). Aksarbin, the improved peptide, showed a favorable in vitro cytotoxicity profile to six cell lines comparable to daptomycin. In vivo, the peptide exhibited a single maximum tolerated dose exceeding 100 mg/kg and demonstrated no toxicity to mice following one week of intravenous injection at the treatment dose of 10 mg/kg. Aksarbin was potent against gentamicin, piperacillin, ceftazidime, colistin-resistant clinical strains, New Delhi Metallo-β-lactamase (NAM) strains, gram-positive MRSA, and extended-spectrum beta-lactamase (ESBL) gram-negative Escherichia coli, P. aeruginosa, and Klebsiella pneumoniae strains. It also showed antibiofilm capability and suppressed bacterial virulence factors based on transcriptomic and proteomic studies. In addition, bacteria did not develop resistance to aksarbin after multiple passages experiment. Significantly, aksarbin demonstrated topical efficacy in S. aureus USA300 infected biofilm wounds, and systemic efficacy in P. aeruginosa-infected bacteremia and overnight infected pneumonia murine models. Combined, these results underscore the advance in designing antimicrobial peptides with systemic efficacy and the therapeutic potential of aksarbin in combating drug-resistant pathogens, especially difficult-to-kill gram-negative bacteria.