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Pretreatment With the Protegrin IB-367 Affects Gram-Positive Biofilm and Enhances the Therapeutic Efficacy of Linezolid in Animal Models of Central Venous Catheter Infection
- Source :
- Journal of Parenteral and Enteral Nutrition. 31:463-468
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- Biofilms play an important role in the pathogenesis of several chronic infections and nosocomial infections related to indwelling medical devices.To assess the efficacy of IB-367 and linezolid (LZD) in the treatment of central venous catheter (CVC) infections using the antibiotic-lock technique, in vitro and in vivo studies were performed. The in vitro antibiotic susceptibility assay for Staphylococcus aureus and Enterococcus faecalis biofilms developed on 96-well polystyrene tissue culture plates was performed to determine the activity of the compounds. Efficacy studies were performed in rat models of Gram-positive CVC infection. Silastic catheters were implanted into the superior cava of adult male Wistar rats. Twenty-four hours after implantation, the catheters were pretreated by filling with IB-367. Thirty minutes later, rats were challenged via the CVC with 1.0 x 10(6) CFU (colony forming units) of S aureus strain diffuse Smith and clinical isolate of slime-producing E faecalis. Administration of LZD into the CVC at a concentration equal to the minimum bacteriocidal concentration observed using adherent cells or at a much higher concentration (1024 microg/mL) began 24 hours later.Both for S aureus and E faecalis, the killing activities of LZD against adherent bacteria were at least 4-fold to 8-fold lower than that against freely growing cells. For both strains, in IB-367-pretreated wells, LZD strongly increases its activity. The in vivo studies showed that when CVCs were pretreated with IB-367, Gram-positive biofilm bacterial load was further decreased to 10(1) CFU/mL and bacteremia was not detected.IB-367 has potential as an adjunctive agent to LZD in the treatment of Gram-positive biofilm infections such as CVC infections.
- Subjects :
- Male
0301 basic medicine
Catheterization, Central Venous
Staphylococcus aureus
medicine.drug_class
medicine.medical_treatment
Antibiotics
Colony Count, Microbial
Medicine (miscellaneous)
Microbial Sensitivity Tests
Staphylococcal infections
medicine.disease_cause
Enterococcus faecalis
Microbiology
Random Allocation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Anti-Infective Agents
In vivo
Acetamides
medicine
Animals
Rats, Wistar
Gram-Positive Bacterial Infections
Oxazolidinones
Antibacterial agent
030109 nutrition & dietetics
Nutrition and Dietetics
Dose-Response Relationship, Drug
biology
business.industry
Linezolid
Staphylococcal Infections
biology.organism_classification
medicine.disease
Rats
Disease Models, Animal
Treatment Outcome
chemistry
Biofilms
030211 gastroenterology & hepatology
Peptides
business
Central venous catheter
Antimicrobial Cationic Peptides
Subjects
Details
- ISSN :
- 19412444 and 01486071
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Journal of Parenteral and Enteral Nutrition
- Accession number :
- edsair.doi.dedup.....50278bf0aebd05d1d6010bd0492a0ac4