*6.5. LL-37 and Tritrpticin*

LL-37, a human cathelicidin, showed an interesting anti-pseudomonas action in neutropenic patients. In a neutropenic mouse model, septic shock was induced by *P. aeruginosa*, and then the groups were randomised into those treated with placebo, imipenem, granulocyte CSF (G-CSF), LL-37 + G-CSF, or imipenem + G-CSF. Although all therapy groups were superior to the control, the LL-37 + G-CSF group was the most effective in preventing sepsis by significantly lowering neutrophil apoptosis in vitro. The authors [75] reported similar results were obtained by *Escherichia coli* 0111:B4 LPS and ATCC 25922 in the murine animal model of sepsis. The authors [76] used treatment groups which consisted of LL-37, polymyxin B, imipenem, or piperacillin vs. placebo. Despite the fact that all treatments reduced lethality, only LL-37 and polymyxin B showed a reduction in endotoxin (≤0.015 ± 0.0 EU/mL and ≤0.015 ± 0.0 EU/mL, respectively, vs. 33.49 ± 4.69 ng/mL piperacillin) and TNF-α plasma levels (0.22 ± 0.01 ng/mL and 0.21 ± 0.01 ng/mL, respectively, vs. 131.12 ± 17.0 ng/mL piperacillin, see Figure 2 from [77]). Furthermore, there were no statistically significant differences in antimicrobial and antiendotoxin activities between LL-37 and polymyxyn B. Given its anti-inflammatory effect, LL-37 is an excellent candidate for the treatment of Gram-negative sepsis. Furthermore, LL-37 was combined with colistin against multidrug-resistant *Escherichia coli*, demonstrating good activity in reducing biofilm formation [77].

Another cathelicidin that has shown activity in vitro against *P. aeruginosa* MDR is tritrpticin, which completely inhibits the procoagulant activity of lipopolysaccharides and shows a synergistic effect with beta lactams [78].
