Background. Morbidity and mortality from Pseudomonas aeruginosa sepsis remain high despite the availability of antibiotics to which the microorganism is sensitive. Methods. The in vitro activity of histatin derivative P-113D was investigated against Pseudomonas aeruginosa. In addition, its in vivo efficacy was studied in 3 rat models of infection: intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysachharide, intraperitoneal injection of 2 × 1010 cfu of P. aeruginosa ATCC 27853, and intraabdominal sepsis induced by cecal ligation and puncture. Rats received isotonic sodium chloride solution parenterally (control groups), 1 mg of P-113D/kg of body weight, 1 mg of polymyxin B/kg of body weight, or 20 mg of imipenem/kg of body weight. Main outcomes measured were abdominal exudate and plasma bacterial growth, plasma concentrations of endotoxin and tumor necrosis factor (TNF)-α, and lethality. Results. The in vivo studies showed that all compounds reduced lethality, when compared with results for the control group. Overall, P-113D exhibited a slightly lower antimicrobial activity than did imipenem, even though P-113D achieved a substantial decrease in plasma concentrations of endotoxin and TNF-α, compared with the imipenem. No statistically significant differences for antimicrobial and antiendotoxin activities were noted between P-113D and polymyxin B. Discussion. These results provide evidence for double antiendotoxin and antimicrobial activity for P-113D and point to its potential use for the treatment of severe infections.
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health