In Situ Tissue Engineering of the Trachea

Antimicrobial Peptides for Gram-Negative Sepsis: A Case for the Polymyxins

“…Although PMB is a commonly used topical antibiotic, it is nephro- and oto-toxic, which, while hitherto precluding its use as an LPS-neutralizer in patients with sepsis, has stimulated the search for non-toxic PMB analogs (Rustici et al, 1993; Porro et al, 1998), PMB derivatives (Vaara, 1983; Viljanen et al, 1991), as well as other structurally diverse cationic amphiphilic peptides (Rustici et al, 1993; Porro, 1994; Iwagaki et al, 2000; Scott et al, 2000; Jerala and Porro, 2004) as candidate LPS-binding agents. Notably, a hemoperfusion cartridge based on PMB covalently immobilized via one of its NH 2 groups to a polystyrene based fiber became available in Japan in late 2000 for clinical use (“Toraymyxin ™ ,” Toray Industries Inc., Tokyo; (Nakamura et al, 1999, 2002, 2003). In the EUPHAS randomized clinical trial, PMB hemoperfusion alongside conventional therapy was found to improve organ dysfunction and reduce 28-days mortality in subsets of patients with sepsis arising from intra-abdominal Gram-negative infections (Cruz et al, 2009).…”