*6.6. IB-367*

The efficacy of topical IB-367, a 17-amino acid synthetic protegrin, was evaluated in a mouse model [79] of a skin wound infected with *P. aeruginosa* or *E. coli*, both MDR, alone and in combination with colistin or imipenem (intraperitoneal). The group treated with IB-367 plus colistin showed the greatest inhibition of both bacterial strains, demonstrating excellent efficacy. In vitro, IB-367 inhibited both bacterial strains with a rapid killing time of 40 min. Therefore, IB-367 may be an excellent candidate for topical therapy of Gram-negative infected wounds in the future.

#### *6.7. Citropin 1.1*

Citropin 1.1 is an amphibian peptide studied alone and in combination with tazobactampiperacillin (TZP) in a mouse model of *E. coli* sepsis. When compared to controls, all treatment groups—intraperitoneal 1 mg/kg cytropin 1.1, 120 mg/kg TZP, or 1 mg/kg cytropin 1.1 plus 60 mg/kg TZP—reduced lethality. The group with cytropin 1.1 alone showed a significant reduction in plasma endotoxins and inflammatory cytokines, while TZP exerted the opposite effect. The combination of cytropin 1.1 and TZP was most effective in reducing lethality, bacterial growth in blood and peritoneum, and oxidative stress indices in plasma. Citropin 1.1 is therefore an AMP with not only antimicrobial but also immunomodulatory properties and may be an interesting option in conditions of severe Gram-negative infection [80].

All of these AMPs are molecules that showed in vivo action against Gram-negative MDR bacteria, suggesting a possible use to overcome increasing antibiotic resistance, as proposed by other in vitro studies. [79–83] However, only some of these molecules, in our opinion, can be developed for use in humans. Particularly in Gram-negative skin infections, an interesting role could be played by IB-367 as the only topical agent to be combined with traditional therapy. Further studies in patients are needed to evaluate both the efficacy and safety of these molecules in humans.
