Greater than 90% of lung infections in cystic fibrosis (CF) patients are caused by Pseudomonas aeruginosa, and the majority of these patients subsequently die from lung damage. Current therapies are either targeted at reducing obstruction, reducing inflammation, or reducing infection. To identify potential therapeutic agents for the CF lung, 150 antimicrobial peptides consisting of three distinct structural classes were screened against mucoid and multidrug-resistant clinical isolates of P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Staphylococcus aureus. Five peptides that retained potent antimicrobial activities in physiological salt and divalent cation environment were further characterized in vivo using a rat chronic lung infection model. All animals were inoculated intratracheally with 10 4 P. aeruginosa mucoid PAO1 cells in agar beads. Three days following inoculation treatment was initiated. Animals were treated daily for 3 days with 100 l of peptide solution (1 mg/ml) in 10 mM sodium citrate, which was deposited via either intratracheal instillation or aerosolization. Control animals received daily exposure to vehicle alone. At the end of the treatment the lungs of the animals were removed for quantitative culture. Four peptides, HBCM2, HBCM3, HBCP␣-2, and HB71, demonstrated significant reduction in Pseudomonas bioburden in the lung of rats. Further in vivo studies provided direct evidence that anti-inflammatory activity was associated with three of these peptides. Therefore, small bioactive peptides have the potential to attack two of the components responsible for the progression of lung damage in the CF disease: infection and inflammation.

Topical prophylaxis against wound infection by an agent that is active against multi‐resistant bacteria does not generate resistance and is rapidly cidal would be of great clinical benefit. Peptides of the innate immune system have long been known to protect a wide range of organisms from attack by bacterial and fungal pathogens. Helix BioMedix Inc. has developed a short bioactive peptide antimicrobial modeled after these peptides. HB‐50 is an amphipathic cationic alpha‐helical peptide that has broad spectrum activity and is rapidly microbicidal. These attributes make HB‐50 an ideal candidate for wound infection prophylaxis. In vitro studies have demonstrated HB‐50 to be active against both gram‐positive and gram‐negative bacteria killing 5–7 log orders of bacteria within minutes. In addition, this peptide has potent activity against Vancomycin and Mupirocin resistant S. aureus. Preliminary testing of the peptide in a rat abraded skin infection model has shown the peptide’s effectiveness in preventing wound infection while not inhibiting wound healing. Additionally, the HB‐50 sequence has been specifically developed to be cost effective to manufacture and therefore is well suited for use as a topical antimicrobial agent.

Peptides of the innate immune system play a vital role in the protection and repair of almost all biological systems. Such peptides have been implicated in a range of activities associated with prevention of disease and modulation of innate immunity. HB107 is a derivative of one such peptide, Cecropin B, that has demonstrated efficacy in enhancing wound healing in both burn and incision animal models. HB107 has been evaluated for efficacy in a mouse incision model and for safety and efficacy in a pig burn wound model. Topical application of the peptide gives RE50(time needed for 50% re‐epithelialization) values of 10.28 days for 500 ug/mL and 12.72 days for 100 ug/mL compared to control 16.45 days. Additionally the peptide was well tolerated in terms of safety both topically and in an IV acute toxicity mouse model with no adverse effects observed. HB107 not only demonstrated efficacy and safety, but due to being a relatively short synthetic peptide, costs significantly less to manufacture than the current approved therapies.

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