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Potential Therapeutic Role of Histatin Derivative P‐113<scp>d</scp>in Experimental Rat Models ofPseudomonas aeruginosaSepsis
- Source :
- The Journal of Infectious Diseases. 190:356-364
- Publication Year :
- 2004
- Publisher :
- Oxford University Press (OUP), 2004.
-
Abstract
- 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 x 10(10) cfu of P. aeruginosa ATCC 27853, and intra-abdominal 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)- alpha, 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- alpha, 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.
- Subjects :
- Male
Imipenem
medicine.drug_class
medicine.medical_treatment
Polymyxin
Intraperitoneal injection
Histatins
Microbial Sensitivity Tests
Biology
medicine.disease_cause
Microbiology
Sepsis
Plasma
In vivo
medicine
Animals
Immunology and Allergy
Pseudomonas Infections
Polymyxins
Rats, Wistar
Salivary Proteins and Peptides
Tumor Necrosis Factor-alpha
Pseudomonas aeruginosa
Abdominal Cavity
medicine.disease
Antimicrobial
Survival Analysis
Rats
Endotoxins
Disease Models, Animal
Infectious Diseases
Polymyxin B
Antimicrobial Cationic Peptides
medicine.drug
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 190
- Database :
- OpenAIRE
- Journal :
- The Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....cccfd818cbb80d15b8bcd722bfae90d2